Liver disease podcast series

Kieran Reynolds
Hello and welcome to our new liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group, where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that healthcare professionals are equipped to manage these patients and that they have an awareness of the risk factors.

My name is Kieran Reynolds, and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co-developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s Hospital and past chair of the British Hepatology Pharmacy Group (BHPG). On today’s podcast, we are delighted to be joined by Sital Shah, Consultant Hepatology Pharmacist at King’s College Hospital London and chair of the British Hepatology Pharmacy Group. Hello and welcome Sital.

Many pharmacy professionals struggle with managing patients with the liver impairment and/or liver disease, and going back to first principles what does the liver do and what are its key functions?

Sital Shah
So, the liver is the largest solid organ in the body, and it has a very important role in detoxifying and in the synthesis of proteins and chemicals necessary for digestion and growth. All blood leaving the stomach and intestine passes through the liver where the liver cells, hepatocytes, process it. The liver has more than 500 vital functions, and I don’t have time to go through all of them, but here are just a few.

So, in terms of its synthetic functions, it’s involved in the production of protein, including albumin, clotting factors, cholesterol, conversion of excess glucose into glycogen for storage and that glycogen can later be converted back to glucose for energy when needed. The liver also produces bile which helps to carry away waste and also helps to break down fat in the small intestine during digestion.

In terms of its metabolic functions, it metabolises carbohydrates, proteins, fats, steroid hormones, insulin, it breaks down red blood cells into bilirubin, and of course drugs and alcohol. It also processes haemoglobin for use of its iron content and stores it too. It converts toxic ammonia to urea. And not many people know this, but the liver is really important for the immune system. It has Kupffer cells which are resident liver macrophages, and these remove foreign debris and particles as well as bacteria and endotoxins that have come from the hepatic-portal system when passing through the liver. And it also stores fat soluble vitamins, as well as vitamin B12 and folic acid.

Kieran Reynolds
So, a really vital organ with many different functions and roles. And for those of you listening who’d be interested in reading more about the functions of the liver, the British Liver Trust About the Liver web page is an excellent resource which we will include a link to within the podcast blurb. Now, for our listeners, we often hear the terms ‘liver disease’ and ‘liver impairment’ used, and Sital, can you help them differentiate between the two, and how would they identify them in practice?

Sital Shah
Yeah, so liver disease and liver impairment are terms that are often used interchangeably, but they refer to slightly different concepts in the context of liver health. So, liver disease is a very broad term that refers to any condition that damages the liver and affects its function. It encompasses a wide range of disorders and abnormalities that can affect the liver’s structure and function. So, for example common liver diseases include hepatitis, so that’s inflammation of the liver; cirrhosis, so that’s permanent scarring of the liver; fatty liver disease, so that’s when there’s excess fat in the liver cells; liver cancer; and liver infections. And this can be caused by various factors including viral infections (like hepatitis B, hepatitis C), excess alcohol consumption, obesity, so being overweight, it could be sort of patients might have genetic predisposition, autoimmune conditions, and toxins or drugs can of course cause liver disease. And the severity of liver disease can vary quite widely, from mild and reversible conditions to more severe and life-threatening ones.

So, liver impairment on the other hand, refers specifically to a reduction in the liver’s ability to perform its normal functions. This can be a consequence of the various different types of liver disease or other factors that just temporarily or permanently impair the liver’s capacity. So, liver impairment means that the functions that I sort of previously described are not being carried out effectively. Now liver impairment can be caused by liver diseases that I just mentioned or by temporary issues such as drug overdoses, most commonly we see paracetamol or other drugs like MDMA, otherwise known as ecstasy. Acute infections can also cause a bit of impairment, acute loss of blood flow such as during a heart attack, or severe malnutrition or dehydration. So, while liver impairment can occur as a result of liver disease, it does not necessarily indicate the presence of a chronic liver disease. So, it could be transient, or it could be temporary that improves with treatment.

So, just to summarise liver disease refers to a broad category of conditions that damage the liver, and liver impairment refers to the reduced function of the liver which can be a result of liver disease or other factors that can be quite temporary.

Kieran Reynolds
That’s great, thank you, Sital. Now we know the importance of disease prevention and nine out of ten cases of liver disease can be prevented. And we as healthcare professionals are really well placed to make interventions and provide advice to patients to reduce the risk of liver disease, and we will address some of these issues in some of our later podcasts.

We can help prevent liver disease by maintaining a healthy weight and staying within the recommended alcohol limits if you drink, and further information is available via the NHS conditions website.

Now, we’ll be discussing this in more detail in one of our later podcasts, but as pharmacists, we’re always interested in how liver impairment affects or potentially affects medicines. What do you think about this, Sital?

Sital Shah
Yeah, so metabolism by the liver is the main route of elimination for many drugs, but luckily the hepatic reserve is quite large, and liver disease has to be quite severe before important changes in drug metabolism occur. So, routine liver function tests, or we sort of call them liver blood tests now, are a poor guide to the capacity of the liver to metabolise drugs, and in the individual patient, it’s not really possible to predict the extent to which the metabolism of a particular drug might be impaired. But what is a bit more useful is actually trying to understand the type of liver disease and the symptoms that may alter the response to a drug. So, for example, we know the liver makes albumin, and if it’s not functioning very well, low albumin can result in an increased risk of toxicity of highly protein bound drugs such as phenytoin or even prednisolone. If there’s reduction in the production of clotting factors, a patient might be at more risk of bleeding when they are say, put on anticoagulation therapy. Now there are certain medications that can increase the risk of impairment of brain function and precipitate something called hepatic encephalopathy, and these are drugs such as opioids or anything that kind of makes the patient feel a bit drowsy. And then drugs that cause dose related toxicity may do so at much lower doses in the presence of hepatic impairment than in someone that has a normal sort of functioning liver.

Kieran Reynolds
So, a really complex organ and clearly a reduction in the functioning of the liver can have complex effects on medicines, and our third podcast will focus on liver impairment and medicines, and we’ll discuss this here in more detail. Now, is there a way to differentiate between different stages of liver disease? We know in liver, or in renal impairment, excuse me, we would calculate the GFR or eGFR, is there an equivalent score in liver disease?

Sital Shah
So, unfortunately not, not for kind of drug use, but liver disease is classified according to the pattern of damage seen and the time course over which this damage occurs. And we can sort of look at the pattern of damage and then use certain scoring systems to try and help us decide on the stages and the severity of liver disease. So, the main patterns of damage can be initially classified as cholestatic or hepatocellular. But these aren’t distinct, they can overlap. So, cholestasis, or cholestatic liver disease occurs when there’s slowing of bile flow through the biliary system, so this is within and outside of the liver. And then hepatocellular, sort of pattern of disease, that’s when there’s damage to hepatocytes, your liver cells, and both of these can lead to fibrosis, which is advanced scaring of the liver and then onto cirrhosis, which is more permanent damage and scaring.

Now unlike renal disease, there is no one measure of liver function, but we do have different scoring systems to help us understand the extent of liver disease. So previously we used to heavily rely on liver biopsies to determine the level of damage, but that’s quite invasive. So, now we use much more sort of commonly non-invasive markers such as blood tests and we can calculate scores such as the FIB-4 score or the ELF (Enhanced Liver Fibrosis) score, to determine the level of fibrosis. And we also have something called FibroScans, and this is a special type of scan that looks at the scarring within the liver and how stiff the liver is because of it. And in this way, we can identify if a patient has fibrosis or cirrhosis.

Now I’m sure a lot of you have heard of the Child-Pugh scoring system, but this was actually originally designed to assess the likelihood of mortality in patients with established cirrhosis that were undergoing major abdominal surgery. But today it’s more commonly used to give us a general indication into how well the individual’s liver is functioning in the context of cirrhosis only. It is not validated to determine medication dosing. So, just a refresher in these scores, a Child-Pugh score of 5 to 6 corresponds to Child-Pugh A, and this indicates actually a relatively well functioning liver, and that’s called compensated cirrhosis. A Child-Pugh score of 7 to 9 corresponds to a Child-Pugh grade of B, and this signifies sort of a significantly compromised liver function. A Child-Pugh score of 10 to 15 corresponds to Child-Pugh grade of C and this indicates decompensation of the liver, i.e., decompensated cirrhosis. But there are newer scoring systems like the Model of End-stage Liver disease or MELD score, or the MELD sodium score now. And these tend to supersede the Child-Pugh score in predicting the likelihood of mortality in patients with liver cirrhosis because they’re a bit more better in terms of their prognostic value and these scoring systems are available online to calculate.

Kieran Reynolds
That’s great and if you’d like to read more about the Child-Pugh score, don’t forget to have a look at our Calculating and Using the Child-Pugh score web page available on the SPS website. Now, one of the most common queries around liver impairment is how to interpret liver blood tests and how to manage abnormal results. Do you have any general advice that you can give our listeners about how to interpret liver blood tests and how to manage abnormal results when they occur?

Sital Shah
Yeah, so liver blood tests give an indication into how well the liver is functioning and can indicate whether there is damage or inflammation within the liver. They can be monitored over hours, over days, weeks or even months to assess whether the liver function is stable, whether it’s improving or deteriorating. The monitoring frequency will depend on the diagnosis. So, when interpreted in isolation, the clinical significance of liver blood tests can often be quite unclear because of normal liver blood tests don’t always indicate the extent of liver damage, they’re not specific to the liver. Results can actually be normal even when someone’s got cirrhosis and some changes to the liver blood tests are quite transient. And like I said, they’re not, liver blood tests aren’t always specific and can be abnormal in the absence of liver disease or affected by conditions just completely unrelated to the liver. So, there are a number of blood tests that relate to liver function, and I’ll discuss each of them now.

So, your ALT and AST indicate hepatocellular damage. So, these are your alanine aminotransferase and aspartate aminotransferase, transaminases. Now these are the enzymes that are found within the liver cells or your hepatocytes. When the liver’s damaged, the ALT and AST levels can increase within hours and remain high for a few days afterwards. The ALT and AST levels can be raised in viral hepatitis, non-alcoholic fatty liver disease (which is now known as metabolic dysfunction associated steatotic liver disease), alcohol related liver disease, autoimmune hepatitis, and drug-induced liver injury. But, they can also be raised in heart disease.

So, your ALP, that’s your alkaline phosphatase enzyme, is a non-specific liver enzyme mainly found in the bile ducts of the liver. Now, when the ALP is raised in conjunction with the GGT, this can indicate cholestasis. It can also slightly be raised in hepatocellular diseases such as primary biliary cholangitis, biliary obstruction and genetic disorders of bile synthesis and excretion, and high levels of ALP can also occur in bone disease. So, if the ALP is high in isolation, then actually you should consider checking the patient’s vitamin D status and also investigating any bone (sort of) related disease.

Now bilirubin is the main pigment in bile, and it’s produced when red blood cells are broken down within the liver. It may be raised in cholestasis, but it can also be raised in hepatocellular disease. So, I briefly mentioned GGT, this is your gamma glutamyl transpeptidase and it’s found in the liver. So high levels of this, like I said, with high levels of ALP, generally indicate cholestasis. But GGT when it’s raised alone can also indicate high, can be high because of alcohol use, or high alcohol use, and GGT levels can be increased up to sort of three times the upper limit of normal in patients with fatty liver disease.

And then finally, we’ve got your INR (international normalised ratio) and your albumin, and these blood tests indicate the synthetic function of the liver. But high INR can also be caused by fat malabsorption and chronic cholestasis because the liver’s not able to store vitamin K as well, and also kind of your liver’s not making clotting factors. Low albumin can also, however, be present in malnourished patients alone. And then finally, low platelets is a good indication of something called portal hypertension as well as decreased platelet production.

Kieran Reynolds
That’s great, thank you. Now you mentioned the patterns of liver damage earlier being either predominantly cholestatic or hepatocellular, but what do these look like in practice? What would a patient’s liver blood tests look like?

Sital Shah
So, with cholestatic liver disease, predominantly you’ll just get rises in ALP, GGT and bilirubin. If someone’s predominantly just got hepatocellular damage, so that’s just damage to the liver cells, you only really see kind of big rises, you know, in your ALT and AST. However, the bile ducts, the liver cells, they’re all within the same place and you can get a bit of a mixed picture where you get both cholestatic and hepatocellular markers.

Kieran Reynolds
Like everything in life, there’s never a single answer!

Sital Shah
No.

Kieran Reynolds
A general pointer for managing deranged liver blood tests is that anything above 2 to 3 times the upper limit of normal requires further investigation or onward referral. And liver blood tests as Sital has said, give an indication into how well the liver is functioning, but they come with a number of caveats, including never look at a single blood test in isolation and always look at the pattern of blood results. Further information is available via the Assessing liver function and interpreting liver blood tests webpage on the SPS website or on the Liver blood tests web page from the British Liver trust.

That’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon. If you have any feedback on this podcast, we would be interested in hearing your comments to help us guide the delivery of the rest of our podcast series, and we’re always keen to hear from you about suggestions you have for resources or events you want us to cover and our contact details are available on the website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up to date content and you will receive news of upcoming events. You can also find out more about the BHPG on the BASL website or follow them on X (formally known as Twitter): @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our new liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group, where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that healthcare professionals are equipped to manage these patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds, and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS, and this podcast series has been co-developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals NHS Foundation Trust and past chair of the British Hepatology Pharmacy Group, (the BHPG).

This is the second in the series, and if you haven’t already tuned in, our first podcast was an overview of liver disease. On today’s podcast, we’re delighted to be joined by Naz Kanani Alviri, Principal Pharmacist in Hepatology and Liver Transplantation from the Royal Free Hospital in London. Hello and welcome to you Naz.

Naz Kanani Alviri
Hi Kieran, thank you for having me today.

Kieran Reynolds
So, firstly, many of our listeners may not be familiar with the term cirrhosis. Can you explain what liver cirrhosis is and how it’s diagnosed?

Naz Kanani Alviri
Of course. So, cirrhosis is defined by widespread disruption to the normal liver structure by fibrosis, which is also known as scarring. And what happens is nodules replace what was previously smooth liver tissue and the liver can become more stiff, and together this scarring and nodules are known as cirrhosis.

Cirrhosis itself is a result of long-term progressive liver conditions that can cause continuous damage to the liver. So, some common causes that you may already be familiar with include alcohol related liver disease [ARLD], MASLD (which stands for metabolic dysfunction associated steatotic liver disease), and this was previously known as non-alcoholic fatty liver disease.

In terms of diagnosis, this is generally based on one or a combination of clinical findings, imaging results such as scans, endoscopy, non-invasive tests (and non-invasive tests include things like transient elastography, which is also commonly known as FibroScan which measures liver stiffness), or blood tests that can indicate advanced fibrosis so that can include FIB-4 or Enhanced Liver Fibrosis [ELF] tests. And cirrhosis can also be diagnosed by a biopsy. It’s important to note that both FIB-4 and ELF, the blood tests that I mentioned earlier, these can be calculated by the GP prior to referral to a specialist service and some areas now actually include these liver screening tests in general health checks.

In cirrhosis, what happens is the function of the liver gradually reduces and patients may have quite non-specific symptoms, and that means that cirrhosis can actually go unnoticed or undiagnosed for many years until patients eventually present with symptoms which I’ll discuss later, and this is why liver disease is often referred to as a silent disease. Unfortunately, in my clinical practice, the way I see cirrhosis most commonly being diagnosed is when patients eventually present to hospital with signs of decompensation such as ascites or bleeding, which we’ll discuss later on. So, it’s quite important to be able to identify these patients early on in their disease.

Kieran Reynolds
That’s great, thank you. Now, because a diagnosis of cirrhosis, as you mentioned, can be based on a number of different factors, it might not be clear if patients actually have cirrhosis. Do you have any hints or tips that can help guide healthcare professionals in determining if a patient has cirrhosis?

Naz Kanani Alviri
Yeah, so, there are quite a few ways of finding that out. I think the first important thing is to ask the patient, so when you’re having that initial consultation, they may know that they have underlying cirrhosis. And also examining the patients, having a look at them are they showing any signs of liver disease, for example, ascites (which they might have a swollen abdomen), do they have jaundice (which includes yellowing of their eyes or the skin), and spider naevi, which is another sign of a liver disease, which is a cluster of blood vessels that you can see under the skin. And the other thing is to have a look at their patient records so to check if the diagnosis of liver disease has been documented or liver fibrosis or cirrhosis. You can also have a look if the patient Is under the care of hepatologist or gastroenterologist or any other specialist who manages liver disease, and also looking at their medication list it may give you some clues as to what medicines they are on for their liver disease, and I can speak a bit later about what kind of medications you can expect to see.

Kieran Reynolds
That’s great, so lots of things that we can actively do to try and figure out if the patient has cirrhosis. Now, in clinical practice, we often hear the terms ‘compensated’ and ‘decompensated cirrhosis’ being used to describe patients with liver cirrhosis, but what do these terms mean?

Naz Kanani Alviri
Yeah, so, when you see a patient with cirrhosis, it is important to understand whether or not they have compensated or decompensated cirrhosis.

Compensated cirrhosis is essentially when the liver is coping despite the damage and scaring that’s happened to the liver, and it can still carry out its important functions and patients will generally be asymptomatic, so they won’t have any signs of liver disease. Transition from compensated to decompensated cirrhosis occurs at a rate of approximately 5 to 7 percent per year. And once a patient reaches decompensated cirrhosis, this is essentially when the liver cannot perform all its functions adequately and people will present with the clinical signs of liver disease that I mentioned earlier, so most frequently they’ll present with ascites, bleeding, encephalopathy, renal dysfunction, and jaundice. An episode of decompensated cirrhosis is generally a medical emergency, and the survival drops by quite a lot once people develop decompensated cirrhosis. So, it drops from over twelve years in compensated cirrhosis to approximately only two years in decompensated cirrhosis.

Kieran Reynolds
Thank you. Now you’d briefly touched on it previously and you mentioned some of the complications of decompensated cirrhosis. Would you be able to now explain a little bit more about them and how they affect patients?

Naz Kanani Alviri
Yeah. So, I’ll start by talking through hepatic encephalopathy. So, this is when patients with encephalopathy, they’ll have symptoms including confusion, what we call sleep-wake cycle reversal, so that will be a change in their sleeping patterns, they might be sleeping more during the day and awake at night, they might have short term memory loss, a loss of concentration so they might not be able to, read a newspaper or follow their regular TV programme. Encephalopathy is quite complex, but it’s thought to be essentially a result of toxins that are usually cleared by the liver accumulating because the liver is now damaged and it cannot clear these toxins as it usually would. The most well-known toxin thought to lead to encephalopathy is ammonia, and this can build up and cross the blood-brain barrier and that leads to the symptoms that I discussed earlier.

In terms of treatment for encephalopathy, most treatments are directed towards the gut to prevent absorption of these toxins and that includes lactulose, which is our usual first line therapy. And our aims of therapy with lactulose is to have at least two to three soft stools per day, and it’s important to note that the doses seen in practice might be higher than what you would usually see for constipation. Another treatment option is rifaximin. So rifaximin given at a dose of 550mg twice daily is a second line agent that’s recommended to reduce recurrent episodes of encephalopathy. This was previously a hospital only medication, but there is the option of shared care now across the country so you may see more prescriptions in primary care for this with requests of shared care with rifaximin.

The other complication of decompensated cirrhosis that patients usually present with most commonly is ascites. This is a fluid buildup in the abdomen and it’s a manifestation of portal hypertension. So, portal hypertension is associated with cirrhosis, and that’s when there is an increase in the blood pressure in the portal vein, and the portal vein is responsible for carrying blood from the bowel and spleen to the liver. So, with portal hypertension, this can cause renal dysfunction, which ultimately can lead to sodium and water retention and hence ascites. In terms of treatment, all patients are advised to adhere to a low salt diet, so no added salt, and also diuretic therapy. The usual diuretics you’ll see in practice includes spironolactone and furosemide. Again, these might be higher doses than you’re used to seeing, so spironolactone doses can range between 100 to 400mg per day and furosemide between 40 to 160 mg per day. Though you may see other diuretics in practice also. In terms of monitoring, patients will be monitored with daily weights, urea and electrolytes, and for any side effects, such as electrolyte disturbances, renal dysfunction, and gynaecomastia with spironolactone. Some patients can be diuretic resistant so their ascites cannot be well controlled with the diuretics or they can also be diuretic intolerant, in that they might develop complications and side effects such as renal dysfunction. And these patients may need to come into hospital regularly to have their excess fluid drained from their abdomen.

Another complication that is associated with ascites is an infection called spontaneous bacterial peritonitis, most commonly called SBP. So, in patients with ascites, there is a risk of infection in the fluid in the abdomen, and that’s what we call SBP. This is associated with a high mortality and requires antibiotics. So, any patients that present with new or any increase in the volume of their ascites, or symptoms such as abdominal pain and fever, they should have that ascitic fluid sent off for white cell count analysis and to also culture to see if any bugs grow. A neutrophil count of over 250 [cells/mm3] confirms a diagnosis of SBP and then these patients will be initiated on antibiotics, initially IV [intravenous]. Once the patient has completed a course of IV antibiotics, they are usually prescribed what we call secondary prophylaxis, because there is a high chance of this [SBP] recurring and obviously because of the high mortality associated with the infection. So, the usual choice of antibiotics you’ll see for long-term [secondary] SBP prophylaxis are ciprofloxacin or co-trimoxazole.

And we also mentioned bleed[ing], so patients, one of the complications of portal hypertension is a variceal bleed, and this is a medical emergency. Once the patient is stabilised, they’ll usually be initiated on a non-selective beta blocker to prevent variceal bleeding from recurring, and the non-selective beta blockers that we use are carvedilol or propranolol in practice. We do prefer carvedilol in practice because it’s been shown to reduce portal pressure to a greater extent than propranolol and also has some anti-alpha-1 activity as well. In terms of monitoring, so it would be as per usual practice, so to monitor patient’s heart rate and blood pressure. It’s also important to note that carvedilol can be given once a day, whereas propranolol typically needs to be given up to three times a day.

Kieran Reynolds
That’s great. So, lots of complications from cirrhosis and patients potentially on lots of medicines, so lots of opportunities for pharmacy professionals to optimise these patients’ medicines. Now, we’ll be discussing this in our podcast in more detail, but as pharmacy professionals, how does cirrhosis impact or potentially impact the recommendations that we make with regards to medicines?

Naz Kanani Alviri
So, the liver itself is quite a robust organ, and many patients don’t necessarily need changes to their medications, particularly while they have compensated cirrhosis. In terms of recommendations that we would give with regards to medicines, these should be patient specific. There’s no one single method that can be used in terms of assessing drug safety in these patients. So, we need to take into account the disease state, if the patient has any signs or symptoms of liver disease, and what their liver function tests are telling you at the time.

In practice, we tend to use the Summary of Product Characteristics [SmPC] to help with our recommendations. And sometimes you’ll notice that in the Summary of Product Characteristics there will be reference to the Child-Pugh score when discussing medication dosing in hepatic impairment and potentially in the contraindications and precaution section. It’s important to know that Child-Pugh score only relates to patients with liver cirrhosis, so that’s the only context within which it can be used. And when it’s referred to in the SmPC, it’s because the studies that support the information have been performed in patients with cirrhosis. The Child-Pugh score itself was actually initially developed to estimate post-operative mortality in those with cirrhosis, and it’s rated from A to C, where A is quite a mild hepatic impairment and C is severe, and so, it describes the severity of liver disease and the associated prognosis. In general, Child-Pugh A would indicate compensated cirrhosis, and Child-Pugh C would indicate decompensated cirrhosis. In patients with Child-Pugh [B] cirrhosis, they may have compensated or decompensated disease and you need to take the patient themselves into account whether or not they’re showing any signs or symptoms of liver disease. One specific example of dose reduction in decompensated cirrhosis is paracetamol. So, in those with decompensated cirrhosis, we actually recommend lower than the usual 4g per day and we would advise a maximum of 1g three times a day. So, 3g daily of paracetamol in those with cirrhosis.

Kieran Reynolds
That’s great and the British Association for the Study of the Liver have published a position statement on prescribing weight adjusted oral paracetamol in adults and we’ll include a link to this position statement within the podcast blurb. For those of you who would like to read more about the Child-Pugh score, you can always have a look at the Calculating and using the Child-Pugh score article published on the SPS website and again we’ll publish a link to it within the blurb.

Now finally Naz, we know that the incidence of liver disease and cirrhosis is increasing but are there any initiatives being undertaken by the NHS to actively to reduce this or to try and identify at risk patients earlier?

Naz Kanani Alviri
Yes, so we discussed earlier how liver disease can be a silent disease and patients will often present to a hospital with signs of liver disease or decompensated cirrhosis which is associated with quite poor survival. So, there’s a really big emphasis on prevention and reduction of risk factors, which I believe will be covered in future podcasts.

And there have recently been a number of launched initiatives that are trying to identify patients with cirrhosis earlier on. An example of this is the NHSE community liver health pilot. So, this may include going to areas such as drug and alcohol services, or diabetes clinics, GP surgeries and FibroScanning patients and trying to detect fibrosis earlier on. There’s a push to increase availability of FibroScans in community diagnostic centres, and also an increase in non-invasive tests, so for example, the blood tests with FIB-4 and ELF in community that can be used to detect potential fibrosis or underlying cirrhosis.

Kieran Reynolds
That’s great with an increased emphasis placed on prevention of disease, it’s really great to see that the liver community is taking an active part in preventing liver disease across the country.

Well, that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon and thank you very much to Naz for all her contributions to the podcast today. If you have any feedback on this podcast, we would be interested in hearing your comments to help us guide delivery of the rest of our series. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up to date content and you will receive news of upcoming events. You can find out more about the BHPG on the BASL website or follow them on X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our new liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group, where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing and it is important that healthcare professionals are equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds, and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co-developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals NHS Foundation Trust and past chair of the British Hepatology Pharmacy Group, (the BHPG).

This is the third episode in our liver podcast series, and we would encourage you all to listen to find out more about liver disease and cirrhosis in our first two podcasts. On today’s podcast, we’re delighted to be joined by Aimee Francisco, Advanced Specialist Gastroenterology Pharmacist at Gloucestershire Hospitals NHS Foundation Trust, and Primary Care Lead at the BHPG. Hello and welcome to you Aimee.

Aimee Francisco
Hello, Kieran, thank you.

Kieran Reynolds
So, to start off, Aimee, we’ve heard in previous podcasts of the important role of [the] liver in the metabolism of medicines, but what are the key things you need to consider when prescribing medicines in liver disease?

Aimee Francisco
So, when prescribing in liver disease, we don’t only need to consider how liver impairment will affect the handling of the drug, but we also need to consider how the drug’s properties will affect the liver disease. So, before prescribing anything, there are a few things that I would want to know: number one, what type of liver disease does the patient have and what is the cause of their liver disease? Is the cause of their liver disease, so for example obesity or alcohol, being treated? And number two, what is the severity of their liver disease? Do they have fibrosis or cirrhosis? And if they have cirrhosis, do they have compensated or decompensated cirrhosis? And number three, what signs and symptoms of liver disease do they have? We need to consider whether the side effect profile of the drug will worsen the patient’s symptoms. And other drugs can cause hepatotoxicity, which may be problematic if there is already underlying liver disease.

In terms of blood monitoring, this depends on the drug and the patient factors that I’ve already mentioned. The SPS medicines monitoring tool gives more specific information for various drugs about what and when to monitor which is really worth a look. Some drugs may also cause transient changes in liver blood tests or liver function tests, or LFTs which I might use interchangeably throughout the talk [podcast], which are not usually clinically significant and are not a total contraindication to their use in liver disease. At any prescribing points we need to consider the risks and benefits of treatment and whether these drug related changes in LFTs will muddy the waters when monitoring the patient’s disease course.

Kieran Reynolds
Great, so lots of things to think about and consider and for those of you who are interested in finding out more, have a look at the two SPS articles: Questions to ask when giving medicines advice in liver impairment and Information resources for managing medicines in liver impairment.

Now, Aimee, what are the key medicines which should be avoided or used with caution in liver disease?

Aimee Francisco
So, it’s really important to consider the side effect profile of medicines when prescribing in liver disease. So, drugs that can cause sedation, so, for example, opioids or gabapentinoids, may further impair cerebral function and precipitate hepatic encephalopathy (or HE). We also need to be mindful of drugs that can cause constipation, so things like antimuscarinics, ondansetron, as these again can precipitate or worsen HE. And we also need to be careful of over-diuresing patients with things like frusemide or spironolactone, because electrolyte imbalances can also worsen HE.

We might also want to be mindful of the medicines that can cause fluid retention, so things like NSAIDs [non-steroidal anti-inflammatory drugs] or corticosteroids because these could worsen the patient’s ascites and/or oedema. And it’s important to consider the sodium content of IV [intravenous] preparations and effervescent tablets in these patients.

Clotting might be impaired in liver disease, so NSAIDs should be avoided, and we need to weigh up the risks and benefits of antiplatelets and anticoagulants or other medicines that can increase the bleeding risks, so things like SSRIs [selective serotonin reuptake inhibitors]. We might also want to consider the risk of variceal bleeding in patients with oesophageal varices, and we would want to avoid [oral] bisphosphonates in these patients.

Pruritus, or itching, might also be a problem for some patients, particularly those with cholestatic liver disease. So, you might want to avoid medicines that have a high risk of causing itching as a side effect, where possible.

If the patient is taking a PPI [proton pup inhibitor], then this should be reviewed and if appropriate, stopped unless there’s a really clear indication. So, for example, ulceration and if so, make sure that the review point is adhered to so that the patient isn’t continued on this inappropriately long term, as not only can it increase the risk of osteoporosis (and patients with liver disease do have an increased risk of osteoporosis), but there is also some evidence that it increases the risk of hepatic encephalopathy and spontaneous bacterial peritonitis (or SBP) due to bacterial translocation.

Also, in advanced liver disease patients might develop hepato-renal syndrome, so in those patients we’d want to be careful of any nephrotoxic agents so medicines that are toxic to kidneys again in these patients.

Kieran Reynolds
And I assume then that many of these medicines could be used with caution, where needed and, with say, extra patient monitoring, if the medicine is indicated and there are no other options?

Aimee Francisco
Yeah, definitely. So, there will be situations where these medicines are indicated. So, for example, we might need to use opioids in patients whose pain relief is not controlled with paracetamol alone. In general, a good motto to follow would be “start low and go slow”. So, use lower doses than you would in general and monitor the response before titrating the dose slowly. Making sure that the patient is counselled on the potential of opioids to cause constipation and lifestyle measures such as increasing fibre intake or pharmacological methods (laxatives) to help prevent constipation is really important as well. And family members can be a really helpful source, so using them to spot the signs of HE and making sure they’re counselled about that.

The British Association for the Study of the Liver (or BASL) has published a really helpful guide on symptom control and end of life care for adults with advanced liver disease and that provides guidance on safer options for symptom control and things to consider in these patients when there’s no available alternatives.

Kieran Reynolds
That’s great and we’ll be sure to include a link to that position statement from BASL within the podcast blurb. Another example of a recommended dose reduction in decompensated cirrhosis is the lower than maximum recommended dose of paracetamol which has also been endorsed by BASL and we will be sure to include a link to this again within the podcast blurb.

Now, Aimee, we hear a lot about medicines that damage the liver but what are the keyways in which medicines cause damage to the liver?

Aimee Francisco
Yeah, so drug-induced liver injury (or DILI) may range from small increases in liver enzymes such as the ALT, for example, to less than three times the upper limit of normal, so nothing insignificant, to symptomatic disease, to acute liver failure or even death.

So, there’s two types of DILI. So, number one is intrinsic, which is predictable, dose dependent and reproducible. So, the most well-known example would be a paracetamol overdose. The second is idiosyncratic which is unpredictable and independent of the dose. So, this means that it can take a number of months for some DILIs to appear and the importance of a very thorough drug history, including creams, over the counter medicines, herbal medicines and supplements, and also recreational drugs is really important when a DILI is suspected.

Aside from pre-existing liver disease, there are other risk factors for DILI and that includes sex, so women are more at risk of a drug-induced liver injury than the men; age, so those over 60 years of age and children are more at risk. So, a common example would be aspirin causing Reye’s syndrome in children. There’s a genetic component. Also, polypharmacy can increase the risk of DILI, so enzyme induction can increase the risk of hepatotoxicity associated with paracetamol, for example. And then comorbid conditions, so pre-existing renal disease, diabetes, and pregnancy can also increase the risk of drug-induced liver injury or DILI.

Kieran Reynolds
So many factors can increase the risk of [a] DILI but are there any specific medicines that are known to cause liver damage and how do they present?

Aimee Francisco
Yes, lots. So, DILI can present in different ways. So, in the case of paracetamol overdose, patients will develop hepatocellular necrosis. So, the patient will present with jaundice, a modestly raised ALP, and markedly elevated ALT, and there will be an increase in the prothombin time.

DILI can also present as steatosis, so where there’s fat in the liver, and in these patients you might see an elevated ALT but not as severe as in the case of hepatocellular necrosis. So, amiodarone is an example of this and might also be associated with chronic steatohepatitis.

Cholestasis can be caused by hormonal contraception. So, this is where there is impairment of the bile flow. And these patients may present with jaundice, dark urine and pale stools, and you would expect to see a raised bilirubin with a normal or mildly raised ALT. In cases of cholestasis associated with hepatitis, then you would expect to see a raised bilirubin, raised ALT and ALP, and some liver damage.

Some medicines can cause liver fibrosis and cirrhosis, such as the case of methotrexate. And in this case LFTs are not necessarily a good indicator of liver damage.

One of the most common questions we get is about statins and liver impairment. So, we know that statins can cause liver impairment and they are associated with mainly mild to moderate serum aminotransferase elevations that are typically transient, asymptomatic and might even resolve with continuation of the statin without dose adjustments. So, it’s important to know that deranged LFTs is also not a contraindication to statins, as long as the serum transaminases are less than three times the upper limit of normals then statins can be initiated.

Kieran Reynolds
Great. And as we’ve already mentioned in the podcast, don’t forget to check out the SPS medicines monitoring tool for further information on monitoring for statins. LiverTox is another great resource, and it is an online resource for information on drug-induced liver injury resulting from prescription medicines over the country medicines, herbal products, and dietary supplements, and we’ll be sure to include a link to this within the podcast blurb.

Now, Aimee, we hear a lot about herbal medicines causing liver damage, are there any specific ones that we should be aware of?

Aimee Francisco
Yes, so lots of patients choose herbal medicines and it’s important that we as healthcare professionals ask them about herbal medicine usage and give them unbiased evidence-based recommendations. As part of any medication history, especially in patients with newly presenting liver impairment, the use of traditional or herbal medicine should be probed.

A really useful peer reviewed resource is the Memorial Sloan Kettering Cancer Center’s About Herbs database, which provides objective and evidence-based information that can be really helpful in judging of herbal medicines, traditional and proven uses, potential benefits, possible adverse effects including liver damage, and also interactions with other herbs or medicines. There’s also the herbal medicines resource via MedicinesComplete, which is really useful and that’s aimed at healthcare professionals.

So, some examples of herbal medicines that are known to be hepatotoxic include: black cohosh, borage oil, kava-kava, mistletoe and valerian but the list goes on, so do you have a little look into it. Some herbal medicines can result in permanent liver damage and in severe cases this has required liver transplantation. So, in general I would recommend patients speak to a pharmacist before starting any herbal medication to ensure they are well informed about potential risks and any potential interactions with prescribed medication.

Kieran Reynolds
That’s great thank you.

So that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back within another episode soon. And thank you very much to Aimee for all your contributions to today’s podcast. If you have any feedback on this podcast, we will be interested in hearing your comments to help us guide the delivery of the rest of our series. And we’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contacts details are available on the website. Please remember to register on the website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up to date content and you will receive news of upcoming events. You can find out more about the BHPG and the BASL website or follow them at X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that healthcare professionals are all equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds and I’m an Advanced Specialist Pharmacist working in the Medicines Use and Safety Team here at NHS SPS and this podcast series has been co- developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals NHS Foundation Trust and past chair of the BHPG.

This is episode four in our liver podcast series, and we would encourage you all to have a listen to the other podcasts available on the SPS website. On today’s podcast we’re delighted to be joined by Arron Jones, Lead Hepatology Pharmacist at Bart’s Health Trust.

So, hello and welcome, Arron. So, Arron, we’ve heard in previous podcasts about liver disease, cirrhosis and in this next series, we’re going to be talking about different causes of liver disease. The first being MASLD, or MASH. For our listeners who aren’t familiar with these terms, could you help explain what these terms mean?

Arron Jones
Hi, Kieran, thank you for having me today. So, MASLD, or metabolic dysfunction associated steatotic liver disease, is globally the most common chronic liver condition. It’s the medical term used to describe fatty liver disease and is caused by having an excess amount of fat or too much fat in the liver. Now just to clear up any confusion, listeners may have previously heard of NAFLD or non-alcoholic fatty liver disease. Recently there’s been a change in the nomenclature surrounding this condition and related conditions. This has been prompted by removal of potentially stigmatising terms from the diagnosis i.e., fatty and alcoholic, and because of the greater understanding of the pathophysiology of the disease and its related risk factors.

So firstly, the overarching term is now SLD, or steatotic liver disease, and that encompasses all causes of steatosis, or excessive fat in the liver. What was previously known as NAFLD is now MASLD, or metabolic dysfunction associated steatotic liver disease. We also now have MASH, or metabolic associated steatohepatitis, which is the more severe form of MASLD and replaces NASH from the previous terminology. Now this change has been a double- edged sword in some respects. For patients, it makes the terminology surrounding their disease more jargony and harder to understand. On the flip side it’s hope dthat patients have a greater understanding of their condition and the associated risk factors empowering them to modify any of these risk factors that are associated with their condition. If you want any further information about this terminology and the different forms of steatotic liver disease, all of this information can be found on the British Liver Trust website.

Kieran Reynolds
That’s great, Arron. So, you’ve mentioned that MASLD globally is the most common chronic liver condition, so how prevalent is it?

Arron Jones
So, MASLD is very common and it’s estimated up to one in five people in the UK have MASLD and rates of MASLD are also increasing with the rising levels of obesity. However, though most cases of MASLD are linked to excess weight, you can still develop this condition even if you have a healthy weight.

So, there’s a variety of different risk factors. Firstly, that we’ve already spoken about briefly are weight in the overweight or obese range, a high waist measurement, type 2 diabetes, a diet with too many unhealthy foods and drinks, low levels of physical activity or spending a lot of time being inactive or sitting down, high blood lipids such as cholesterol, high blood pressure, and then other conditions linked to insulin resistance.

Kieran Reynolds
So, we know what it is and we know that it’s really common, but how is MASLD or MASH diagnosed?

Arron Jones
So, it’s important to note like a lot of other liver conditions, both MASLD or MASH are often asymptomatic. Steatosis of the liver is normally found through imaging, such as an ultrasound of the liver or abdomen and this might be prompted by abnormal liver blood tests, most commonly, something like a mildly elevated transaminase, so like ALT or AST and GGT. This can be found incidentally as part of routine investigations. It’s also important to note that much, kind of, further along the pathway, this condition can also be identified by a liver biopsy, but not all patients require that. It’s important that alternatives causes of liver disease (i.e., immune mediated, or alcohol related liver disease) are ruled out. MASLD is then diagnosed based on the presence of steatosis of the liver and one or more of the following cardiometabolic risk factors: obesity, so a BMI over 25 or if Asian ethnicity, a BMI over 23 or an increased waist circumference; pre-diabetes or type 2 diabetes; dyslipidaemia or on lipid lowering therapy; hypertension or on blood pressure lowering therapy.

Assessment of fibrosis normally kind of follows on from this initial diagnosis. So, something like a FIB-4 score can be calculated in the community using blood test results and that uses age, AST/ALT and platelets and then across the country as well new initiatives are being established to evaluate fibrosis prior to referral to secondary care for these patients. This includes things like intelligent liver function tests (or iLFTs), reflex ELF testing, and fibrosis assessments in community diagnostic centres with a FibroScan.

Generally, people with no liver damage or, i.e., no significant scarring of the liver can be managed by their GP, while patients with elevated fibrosis scores should be referred to secondary care for further assessment and management.

Kieran Reynolds
That’s great. So, as a healthcare professional and thinking specifically about pharmacy professionals in primary care, how would they know if a patient has MASLD or MASH?

Arron Jones
OK, so I think, you know, the first resource you’re using is the patient, ask them, they might know already, they might describe it as something like having a fatty liver or fatty liver disease. They might not know if they have MASLD or MASH, but they’re kind of your first point of call. Obviously looking at the patient record as well to see if a diagnosis of MASLD or MASH is documented anywhere on patients’ histories and then if patients are under the care of hepatologists, gastroenterologists or other specialists for management of liver disease.

Healthcare professionals working in the community, including community pharmacists, won’t have an active role in the diagnosis and management of these patients, but they will be able to identify those with risk factors for MASLD and provide appropriate advice. One of the key objectives for the NHS is to switch from treatment to prevention and we will discuss later in the podcast how primary care pharmacy professionals can contribute to the management of these patients.

Kieran Reynolds
That’s great. So, my next question is, how are these conditions treated?

Arron Jones
OK. So, it’s important to note that we don’t have any therapies currently licenced in the UK to treat MASLD or MASH directly, but, one of the main things we can do is mitigate or reduce the cardiometabolic risk factors (i.e., obesity, type 2 diabetes) that contribute to the disease. In early stage MASLD, when the liver has little or no long-term damage or scarring, the steatosis, or the fat in the liver can be reversed by eating healthily, by doing plenty of physical activity, and by keeping your weight in the healthy range, you have a good chance of kind of having that fat leave the liver and repairing that damage.

Obesity, particularly abdominal obesity and type 2 diabetes, have the strongest impact on progression to liver cirrhosis, development of liver cancer or hepatocellular carcinoma. So, for obesity, the first line therapy is lifestyle changes and patients should aim for a weight loss between 5 and 10% of body weight to reduce that fat in the liver (or steatosis) and improve the inflammation in the liver. A Mediterranean style diet is recommended alongside limiting consumption of ultra processed foods and high sugar drinks. The most important thing really is making sure the lifestyle changes are long-term and adherence to these lifestyle changes can be maintained. Exercise is also recommended, so 150 minutes a week of moderate intensity, or 75 minutes a week of high intensity with a mix of aerobic exercise, that’s things like running, swimming, and then resistance training, so, training a muscle against resistance, that could be things like gym machines, dumbbells, body weight exercises, and it’s important to note that exercising can reduce steatosis even without significant weight loss.

Another really key intervention is smoking cessation, as well as reducing alcohol intake and avoiding alcohol completely i the presence of cirrhosis and advanced fibrosis, alright. Referral to smoking cessation services should be definitely be considered for these patients, if they are smoking and pharmacists are very well placed to provide that advice and signposting in the community to these services and might even be able to provide it[smoking cessation services] themselves. It’s also really important to note that, you know, these lifestyle changes may not take effect after one interaction or one conversation, it might need repeating multiple times, you know, patients might make a very good start and then you know, kind of, not do as well as they’d hoped and might need a bit of encouragement later on down the line to kind of get back to it.

Kieran Reynolds
And on that note, we must highlight that SPS have developed two national PGD templates for smoking cessation for varenicline and cytisinicline and both of these are available on the PGD templates page.

Arron Jones
That’s great, thank you. Now, I think the most important thing about lifestyle change is individualising this to the patient and their own preferences, clinical, cultural and economic characteristics, like you, how you would individualise a medical treatment when it’s prescribed. For instance, instead of the Mediterranean diet, or the NHS Eat Well guide, which are both excellent resources and I use them all the time in my practice, an alternative is the South Asian Eat Well guide. One of the best things I’ve, kind of, found from speaking to patients and, kind of, give like targeted lifestyle advice is asking them about a food diary, i.e., asking them what they ate yesterday for breakfast, lunch, dinner and then snacks and it’s really a good way to get an understanding of their habits and this is really, really helpful as well if patients are saying that they’re making changes but they’re not losing any weight.

Similarly to exercise, many patients have mobility issues or injuries. Walking is a really easy initial intervention for a large number of patients, and most patients now also have a smartphone, so aiming to increase their daily step count over time is a really easy way to get them more active. I don’t think many, very many patients are going to go from being completely sedentary to doing 150 minutes of exercise per week, so, you know, it’s all about these slow gradual changes that patients can stick to long-term and that they can integrate into their lives.

And then finally, some centres might have a kind of specialist dietician who can provide advice and support to help with this. Patients can also be referred to specialist weight loss services to get access to weight loss interventions such as weight loss medications or bariatric surgery.

Kieran Reynolds
That’s great. And we’ll include a link to both the NHS Eat Well guide as well as the South Asian Eat Well guide within the podcast blurb.

Now, Arron, you’ve mentioned previously about medicines optimisation for type 2 diabetes. Can you give us a little bit more information about this and what other medicines could potentially be optimised?

Arron Jones
Yeah, sure. So, optimisation of type 2 diabetes should be the aim of all patients regardless of if they have MASLD or not, but, and that medicines optimisation should be in line with local or national guidance. There is also a lot of excitement at the moment for the GLP-1 receptor agonists, such as semaglutide, tirzepatide, but not only for type 2 diabetes and obesity, but also for MASLD/MASH because of their beneficial effect on cardiometabolic outcomes and we’ll discuss this a little bit later on. The other modifiable risk factors include hyperlipidaemia and hypertension, and hypertension should always be managed in accordance with national guidance. Patients with chronic liver disease without cirrhosis, or those with compensated cirrhosis requiring statins should be managed as per the national lipid management pathway and they shouldn’t be routinely excluded from statin therapy either.

Kieran Reynolds
And on that note, SPS have developed a resource specifically discussing the use of statins in liver impairment and we will include a link to this within the podcast blurb.

Arron Jones
Yeah, and please note that everything we’ve kind of discussed today is primarily for patients with compensated cirrhosis or no liver cirrhosis at all. Management of risk factors and patients with decompensated cirrhosis is much more complicated and should be done on a case-by-case basis.

Kieran Reynolds
Now, as you’ve mentioned the GLP-1 receptor agonists, are you seeing many patients accessing these medicines for MASLD privately, and what advice would you give to them?

Arron Jones
So, while GLP-1 RAs [receptor agonists] are not currently licenced for MASLD or MASH in the UK, they are licenced and commissioned for use in patients with type 2 diabetes or obesity. For patients with MASLD or MASH, access to GLP-1 RAs would typically be through these existing commissioned indications, and it’s important to remember that these treatments should be used in combination with a calorie restricted diet and increased levels of physical exercise. There’s been quite largely publicised international supply issues with a number of the different GLP-1 RAs, though supply is largely improved now. Given the large eligible population, the full rollout for NHS patients is expected to take a number of years and prioritising those with the greatest clinical need and therefore patients may decide if they can, to access these medicines privately. For patients who are accessing these medicines online, the GPhC have published a guide with other UK health organisations to help people keep safe if they use, they choose to decide to use online services.

Kieran Reynolds
And having mentioned that resource we will be sure to include a link to this resource within the podcast blurb also.

So, Arron, you’ve told us that the cornerstone of MASLD or MASH management is lifestyle modifications, including weight loss and optimisation of modifiable risk factors, but are there any new treatments on the horizon that will be specifically targeted to treat these conditions?

Arron Jones
Yes, there are a number of treatments in development, but I’ll speak about one that has just been submitted to NICE: resmetirom, a thyroid hormone receptor beta agonist is currently licensed in the USA for non-cirrhotic patients. Clinical trials have shown an improvement in fibrosis scores in 26 to 30% of patients with moderate to advanced fibrosis. A submission to NICE has been made for this treatment and a multiple technology appraisal alongside semaglutide for treatment of MASH is now under progress.

Kieran Reynolds
That’s great, so exciting times ahead!

So finally, Arron, how can community pharmacy professionals contribute to the management of these patients and what advice can they give to them?

Arron Jones
So, community pharmacy professionals are well placed to identify those potentially at risk of MASLD or MASH and, particularly with the cardiometabolic risk factors we’ve described. And they can also provide general public health advice, signposting to other services, you know, we talked a bit already about smoking cessation services or provision of these services themselves, signposting to exercise programmes, you know, things like smartphone step counters, the couch to 5K app, and then signposting to healthy eating resources as well, some of which we’ve also discussed earlier. And, kind of, all of these activities are encompassed within the Healthy Living Pharmacy, an essential service requirement for all pharmacies, which is a framework aimed at achieving consistent provision of a broad range of health promotion interventions through community pharmacies to meet the local needs. And the hope is that this will improve the health and well-being of the local population and help to reduce health inequalities. The other, you know, big thing that community pharmacy professionals can provide is medicines usage reviews when they’re commissioned and that ensures patients know why they’re taking the medicines prescribed to them and determine if they’re taking them as intended, and then patients can also be counselled on the importance of adherence to these treatments and hopefully empowered to improve their lifestyles.

Kieran Reynolds
That’s great, thank you, Arron. So that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon. And thank you, Arron, for all your contributions to today’s podcast. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will ensure that you’re always informed of our most up-to-date content and you will receive news of upcoming events. You can also find out more about the BHPG on the BASL website or follow them on X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that healthcare professionals are all equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds, and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co-developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals [NHS] Foundation Trust and past chair of the BHPG. This is episode five in our liver podcast series and we would encourage you to listen to the previous podcasts available on the SPS website.

On today’s podcast, we’re delighted to be joined by Sonal Patel, Lead Hepatology Pharmacist at Guy’s and St Thomas’ Trust and current Chief Pharmaceutical Officer’s Clinical fellow at the General Pharmaceutical Council, the GPhC. Hello, and welcome, Sonal.

So, in previous podcasts we’ve heard about liver disease, cirrhosis, and in this next series we’re going to be talking about different causes of liver disease, the focus of today’s podcast being autoimmune hepatitis, or AIH. And Sonal, for our listeners who aren’t familiar with this condition, can you help explain what it is?

Sonal Patel
Of course, and thanks, Kieran, for having me on this podcast. So, autoimmune hepatitis, or AIH, is generally a chronic condition of the liver, which results from the body’s immune system causing damage and inflammation to its own healthy liver cells. So, overtime if left untreated, that inflammation can cause scarring of the liver leading to fibrosis and in more severe cases this can lead to cirrhosis and even liver failure. So sometimes patients with AIH can present more suddenly and aggressively with an acute hepatitis. This form comes on quite quickly and can cause more severe symptoms like jaundice and acute liver failure.

In a healthy immune system, our lymphocytes, or our B cells, protect our body by producing antibodies against foreign substances like bacteria and viruses. These antibodies will flag these foreign substances for destruction by other forms of lymphocytes, such as T cells. In autoimmune disease, your B cells produce what are known as autoantibodies, which are essentially antibodies against your own healthy cells. So, your immune system is triggered to inappropriately attack your own cells, resulting in inflammation and cell damage. Now in the case of AIH, this inappropriate immune reaction causes damage specifically to your liver cells.

So, AIH is classified as a rare disease, it affects up to 10,000 people in the UK and like many other autoimmune conditions, there’s no known single, clear cause. There are a few things to note, however. So, AIH is more common in women, so 80% of cases occur in females. There’s a genetic link: up to 50% of people with AIH might have a family history or personal history of other autoimmune diseases. And in those with a genetic predisposition, environmental factors like viral infections or certain medications might trigger the condition.

Kieran Reynolds
That’s great. So, now that we know what AIH is, what are the symptoms of AIH, or autoimmune hepatitis, and how do they differ from the symptoms of other liver diseases?

Sonal Patel
Thanks, Kieran. So, similar to other types of liver disease, the symptoms of AIH can be quite general and non-specific. So, symptoms like extreme fatigue, joint pain, nausea, flu-like symptoms, itching, sometimes discomfort around the abdomen or weight loss can be experienced. Lots of people living with AIH don’t experience any symptoms at all, which is why it’s often called a silent disease. And up to third of patients with AIH will present with cirrhosis, and some of these patients may even have developed liver cancer, [which is also known as hepatocellular carcinoma), by the time AIH is diagnosed. So, as you’ve previously discussed in this cirrhosis podcast, liver function gradually declines in cirrhosis and often it’s accompanied by non-specific symptoms. So, as a result the condition can remain undetected for some time until noticeable symptoms will prompt further investigations and tests.

Kieran Reynolds
Great. So, the symptoms of AIH are generally non-specific. So how is it diagnosed in patients?

Sonal Patel
So, diagnosis of AIH involves looking at both the patient’s clinical history and various investigations or tests. So, liver blood test results, such as ALT [alanine aminotransferase] or AST [aspartate aminotransferase] might be raised. We also check for the presence of auto antibodies such as anti-mitochondrial antibodies (or AMA), anti-nuclear antibodies (or ANA), and anti-smooth muscle antibodies (or ASMA). We check for immunoglobulin levels, specifically IgG [immunoglobulin G], which is another type of antibody within blood tests, although these aren’t always abnormally raised in patients with AIH.

There may also be some imaging or scans conducted, such as a FibroScan which measures liver stiffness, or an ultrasound of the liver. Really, a liver biopsy is needed to confirm diagnosis. So, here a sample of liver tissue is taken and examined with the support of a histopathologist, and then the diagnosis can be made by considering all of the investigations together; so, the clinical history, the lab results, imaging findings, and the overall biopsy result. So, as you can see, AIH isn’t always the easiest disease to diagnose. There’s lots of factors which can cause what we call diagnostic confusion. It can also coexist with other types of the liver disease like primary biliary cholangitis (or PBC), or primary sclerosing cholangitis (also known as PSC), and that can also complicates the picture further.

Kieran Reynolds
And we will be discussing PBC, or primary biliary cholangitis, in a future podcast so be sure to tune in for that. And for those who want to learn more about liver blood tests that Sonal has mentioned, SPS have developed a resource around interpreting liver blood tests and we will include a link to these within the podcast blurb.

So now we know how AIH is diagnosed, the next question is: how is it treated?

Sonal Patel
Yeah, so, it’s important to note there’s no complete cure for AIH, but there are effective treatments available, and the main goal of treatment is really to reduce inflammation and prevent further damage or scarring of the liver.

So, in simple terms, the treatment for AIH usually starts with steroids, and these work quickly to bring the inflammation under control. And then long-term immunosuppressants are used to help maintain remission and prevent the disease from flaring up again. So, when we’re assessing response to treatment, we monitor liver blood tests like, ALT and AST, and the immunoglobulin IgG, with the aim of getting these markers back into the normal range, and this gives an indication that the inflammation is being controlled and there’s no further damage occurring to the liver.

So, as I mentioned, oral steroids are often the first line in treating AIH, and just like with many other autoimmune conditions, because they’re effective in really quickly reducing that inflammation. The goal is to gradually reduce the steroid dose over about 6 to 12 weeks to the smallest possible dose and if possible, eventually stop them completely. So, the two main steroids we use in AIH are prednisolone and budesonide. Prednisolone is more likely to be used in patients who present with more severe cases of AIH. One of the benefits, however, of using budesonide is that it has fewer systemic side effects compared to prednisolone because it has a high first pass metabolism. So, that means that 90% of it is metabolised by the liver before it even enters the bloodstream. So, we therefore see fewer steroid related side effects such as weight gain, osteoporosis, diabetes, adrenal suppression, compared with prednisolone. So, it’s therefore a good option for those who might have had problems with steroid side effects in the past. Importantly though, we have to remember that budesonide is contraindicated in patients with cirrhosis, and that’s because hepatic metabolism is reduced in cirrhosis, resulting in higher systemic levels of the budesonide and that consequently increases the risk of the steroid related side effects. And then how long patients need to stay on steroids will be determined on a case-by-case basis. So where possible, the aim is to stop steroids eventually. However, some patients do need to stay on a low dose steroid in combination with the immunosuppressant to keep the inflammation under control.

So, moving on to immunosuppression, the main immunosuppressants we use for long-term treatment are either azathioprine, 6-mercaptopurine, mycophenolate or tacrolimus. Usually, the immunosuppressants will be started a few weeks after steroids, once liver blood tests have started to normalise. It’s important to know that immunosuppressants don’t work right away. They can take up to three months to show their full effect. But once patients are stable on their immunosuppressant therapy, most will continue treatment long-term, usually lifelong. In some cases, we might consider stopping treatment after a few years, depending on the patient’s response and the condition of their liver. But the relapse rate is quite high, so it’s between 50 to 90% chance of relapse, which is why most patients remain on treatment long-term.

So how do we choose which medication to go on? The choice really depends on individual patient factors and their response to tolerance and treatment. Generally, azathioprine is first line immunosuppressant we use but it can cause side effects. 6-mercaptopurine can be used as an alternative in those who can’t tolerate azathioprine. Occasionally, the azathioprine is used with allopurinol to boost its efficacy and reduce the risk of liver toxicity, but this sort of combination requires specialist input for dose adjustment and initial monitoring. Mycophenolate is the other alternative for azathioprine intolerant patients. It’s often preferred in the elderly due to lower risk of certain forms of cancer, but remember that it’s unsafe to use in pregnancy. And finally, tacrolimus is reserved for patients who don’t respond to first-line treatments. It can be used alone or in combination with some of the other immunosuppressants in specialist cases. And then finally, in really resistant cases, biologic treatments such as rituximab might be offered by some specialist liver team[s]. But we have to remember that local formulary agreements or agreed funding arrangements may need to be in place for this.

So, in terms of who prescribes and monitors treatment, treatment is started by specialist teams in hospital and initially doses are adjusted and closely monitored by them until the patient is stable on treatment. So, as a specialist pharmacist, I would be responsible for initiating immunosuppressants and adjusting the dose based on tolerance and response as well as weaning down the steroids. Once the patient was stable on treatment, some centres might have a shared care protocol in place. So, this means that patients can get their routine monitoring tests and medication from their GP, so they don’t need to come to hospital as often. However, the overall disease management is still overseen by the specialist team at our trust. So, we still see stable patients at least once or twice a year.

Kieran Reynolds
That’s great and thanks for bringing us through that, all the treatments for AIH, there’s quite a lot of medicines involved. Now these medicines are all quite high-risk medicines, and they can cause significant side effects. How are patients counselled, and do you have any useful resources that we can signpost our patients to?

Sonal Patel
Yeah, absolutely. I mean we invest a lot of time in counselling patients about their treatment in our pharmacist-led clinics and this is really to help them understand the importance of firstly, good adherence to their treatment. You know, we know adherence can be difficult in chronic conditions, particularly in conditions which don’t have any apparent symptoms. So, you know, we explain to patients that firstly their dose of their medication may change depending on how they respond to and they tolerate their treatment, it might be slowly increased or decreased particularly in the first few months of treatment.

It’s also really important to counsel on potential side effects of the different medications as you mentioned, so that patients know what to expect and they know how to contact us, their specialist teams, should they experience any issues. Now, there are some side effects which are more common, especially in the first few weeks of treatment. Azathioprine and mercaptopurine, for example, can cause flu like symptoms, muscle ache, dizziness and nausea when first started. These symptoms usually do improve within the first few weeks. Mycophenolate can cause nausea and diarrhoea and if this continues beyond the first few weeks then we might need to adjust the dose or review the treatment completely. And then tacrolimus can commonly cause pins and needles. It can also cause changes in blood pressure and blood glucose, so these need to be monitored whilst the patients [are] on treatment.

Now, all of these medicines, including steroids, will affect the immune system, so we also explain to patients that they might take longer to recover from any infection. Patients should report any kind of signs of high fever, unexplained sore throat, ongoing cough or breathlessness to their specialist team, or their healthcare professionals that they’re seeing. And they’re also told to report any unexplained bruising or bleeding, any signs of jaundice, so yellowing of the eyes or skin. And then, specific to sort of mycophenolate and azathioprine, they’re associated with an increased risk of skin cancer as well. So, we would advise patients to take extra precautions, especially when in the sun; so wearing a sun hat and long sleeves, using a high SPF sun cream (minimum factor of 30 SPF, if possible), and also to avoid things like tanning beds, or lying out in the sun for extended periods of time.

Now we all know steroids have well known side effects as well, and that includes changes to blood sugars, weight, and mood, and many of our patients will be on steroids for lengthy periods of time which can also suppress their own ability to produce cortisol. So, it’s important they don’t stop their steroids suddenly or continuously skip doses and they should only reduce or stop their steroids as advised by their specialist team. And steroid emergency cards are given to patients, and they should be shown to any other health care professional involved in the patient’s treatment.

Kieran Reynolds
And the NHS website contains some useful information about some of the medicines commonly used to treat AIH, including prednisolone, budesonide [webpage no longer available] and azathioprine and we will include links to these resources within the podcast blurb. In addition, the Society for Endocrinology’s website has also some useful information on adrenal crisis, steroid sick day rules, carrying a steroid emergency card, and a really useful patient information leaflet, and again we will link to this resource within the podcast blurb. And finally, the BHPG are currently producing some patient information leaflets for medicines commonly used within hepatology, and once these are finalised, they’ll be published and available via the British Liver Trust website.

So, Sonal, my next question is about these immunosuppressants and how are patients who are on them monitored long-term?

Sonal Patel
Yeah, so, at the start of treatment we monitor blood tests quite frequently, things like full blood count (or FBC), liver enzymes (especially ALT and AST), immunoglobulin levels, and renal function are monitored every few weeks until the patient’s more stable on their medication. So, for patients on azathioprine or tacrolimus, we’ll also keep an eye on drug levels in the blood as we adjust doses. Once patients are stable on treatment, the frequency of those blood tests usually reduces to every few months.  And then in terms of scans, a FibroScan is typically repeated once the inflammation is under control, so, around six to nine months into treatment, to check for any signs of fibrosis or cirrhosis. For patients who are cirrhotic, regular ultrasounds might be required as part of liver cancer surveillance, since they are at higher risk of this. And additionally, some patients with cirrhosis will also have regular endoscopies, so camera tests, every few years to check for any varices, so, these are swollen veins within the GI tract which can be at risk of bleeding.

Kieran Reynolds
And the SPS monitoring tool contains recommendations on monitoring for corticosteroids, azathioprine, 6-mercaptopurine, mycophenolate and tacrolimus and this is accessible via the SPS website.

So, Sonal, you’ve mentioned that these patients are generally diagnosed and managed within specialist teams, but how can primary care pharmacy professionals help support patients with autoimmune hepatitis?

Sonal Patel
Thanks, Kieran, there’s lots of things that primary care pharmacy professionals can do to help support this patient group. So, in the early stages of treatment, the main support needed is really to help supply prescriptions for steroids along with calcium and vitamin D supplements, if those have been initiated, and any additional osteoporosis management, if that’s needed as well. The primary care pharmacy professionals conducting medicines reviews can help identify patients on these long-term steroids who might need GI protection, for example, but who aren’t receiving it, as well as ensuring that these patients are getting enough of their, as I’ve mentioned, calcium and vitamin D to reduce the risk of osteoporosis. We also ask patients to stay up to date with their ‘flu, their pneumococcal and COVID-19 vaccines, and in some cases, we also recommend shingles vaccinations. So, we always appreciate primary care support with arranging these. And there’s further information about the eligibility of vaccines in the Green Book, which is a sort of open access document which you can look for online.

Once patients are more stable, we might ask primary care to take over prescribing of immunosuppressants and routine blood monitoring as part of as I’ve mentioned before, the shared care protocol. So, it’s also important to be mindful of any potential drug-drug interactions when new medications are prescribed in primary care. This is really relevant for medicines like tacrolimus, as its levels can be affected by inducers and inhibitors of the cytochrome P450 enzyme system, so medicines like clarithromycin and fluconazole can interact with it and change levels. It’s also important to be aware that for some patients medicines used to treat AIH may not appear on their National Care Record, so they may just be prescribed by their hospital team and not the GP. So, it really emphasises the importance of taking a thorough drug history from multiple relevant resources.

And then in terms of ongoing checking for adherence, this is something that’s really important. Simply asking patients how they’re getting on with their medicines can make a big difference. If they raise any issues or they mention they’ve stopped taking their medicines, it’s really valuable to be able to signpost them back to the specialist team for further support. And what we find is generally primary care teams and community pharmacists often have a closer relationship with patients, particularly if they’ve known them for many years, and that sometimes makes it easier for them to open up if they’re having difficulties with treatment. So, if you notice, for example, that liver blood tests are becoming consistently unstable and it’s unexplained, it could be a sign of poor adherence, or that something else is going on. So, flagging these concerns to the specialist team can really help ensure patients get the right support as early as possible.

Kieran Reynolds
That’s great. And to add to those, AIH support is a charity which aims to provide information and support to people affected by AIH and patients can be signposted to their resources for further information. And also, the British Liver Trust is a really useful resource and provides support and advice to patients.

So, that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon. And thank you very much to Sonal for all your contributions to today’s podcast. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up-to-date content, and you’ll receive news of upcoming events. You can also find more about BHPG on the BASL website, or follow them on X @heppharm and you can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service (SPS), in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that healthcare professionals are all equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co-developed with Helen Boothman, lead Hepatology Pharmacist at St George’s University Hospitals NHS Foundation Trust and past chair of the BHPG. This is episode 6 in our liver podcast series, and we would encourage you to listen to the other episodes available on the SPS website.

On today’s podcast we are delighted to be joined by Yun Jung Kim, Senior Specialist Pharmacist in Hepatology at the University Hospital Southampton NHS Foundation Trust and vice-chair of the BHPG.

Firstly, hello and welcome to you, Yun.

Yun Jung Kim
Hello.

Kieran Reynolds
So, Yun, we’ve heard in previous podcasts about liver disease, cirrhosis, and in this next series we’re focusing about different causes of liver disease, and the topic of our conversation today is about Primary Biliary Cholangitis, or PBC. For the listeners who haven’t heard this term before or aren’t familiar with it, can you help explain what it means?

Yun Jung Kim
Yes, of course. Primary Biliary Cholangitis, or PBC for short, is a chronic autoimmune liver disease that primarily affects women, although it’s increasingly being recognised in men as well. It occurs when the immune system mistakenly attacks and damages the small bile ducts inside the liver and these bile ducts are responsible for draining bile, which helps digest fats and remove waste from the body. When the ducts are damaged, they narrow and become distorted, causing bile to build up in the liver and this build-up leads to inflammation and scarring, a process known as fibrosis. If left untreated, PBC can progress to cirrhosis and eventually liver failure. However, with early diagnosis and appropriate treatment, most patients can manage the condition and maintain stable liver function.

Kieran Reynolds
Great. So now we know what it is, my next question is, well, what are the symptoms of PBC?

Yun Jung Kim
As has been mentioned in previous podcasts, many of the symptoms of liver disease non-known specific and often liver disease is only diagnosed after tests or investigations, including scans for another medical reason. For many people with PBC, two of the most common reported symptoms are fatigue and itch, also known as pruritus. These are symptoms can occur at any stage of the disease and interestingly, aren’t necessarily linked to how advanced the liver damage is. Fatigue in particular affects over half of all patients and can be severe in about one in five, significantly impacting day-to-day life. It may include poor concentration or memory, sometimes mistaken for other conditions. Now there’s no specific treatment, structured approach focusing on contributing factors such as anaemia, thyroid problems or medications can help people managing it better.

Pruritus or itching affects about 80% of people with PBC at some point. It’s a hallmark symptom of cholestasis, when bile flow from the liver is reduced, and while it might sound minor, it can be extremely distressing. Patients often describe a deep, unrelenting itch that isn’t helped by scratching and sometimes making their skin raw or damaged in the process.

Another common symptom in PBC is what’s known as the sicca complex, and this includes dry eyes, dry mouth, and sometimes difficulties swallowing. Most people experience mild sicca symptoms rather than having full blown Sjögren’s syndrome.

Artificial tears, saliva substitutes, and good oral hygiene are simple, yet effective options for many.

Kieran Reynolds
Thank you. And some of those symptoms, as you said, do sound really debilitating. So how is PBC diagnosed and is it different from any other liver diseases and how they’re diagnosed?

Yun Jung Kim
So, PBC is diagnosed through a combination of a blood tests and the clinical assessments and in most cases, a liver biopsy isn’t required. One of the key markers is a persistently raised alkaline phosphatase (ALP) level, which shows up in liver blood tests. If this is the case, the next step is to check for anti-mitochondrial antibodies [AMA], auto antibody which is present in about 90 to 95% of PBC cases. So, if both ALP is elevated and anti-mitochondrial antibody is positive, that’s usually enough to confirm the diagnosis.

In case where AMA isn’t detected, other autoantibodies like antinuclear antibodies (ANA), including anti-gp210 or anti-sp100, may support the diagnosis, though these are normally tested in specialist settings. Imaging or scans such as ultrasound can also help, though it’s mainly used to rule out other causes of cholestasis like bile duct obstructions. In some rare cases, especially when blood tests aren’t conclusive or when there is a suspicion of overlap with other autoimmune liver diseases, a liver biopsy may be needed.

So, in summary, raised ALP or positive AMA and the exclusion of other causes are the main criteria for diagnosing PBC, typically by a specialist in secondary care. However, it’s often primary care that first notices the abnormal liver blood tests.

Kieran Reynolds
That’s great. Thank you and we’ll include some web-based resources from the British Liver Trust around diagnosing PBC within the podcast blurb. Now as a healthcare professional, and I’m thinking especially pharmacy professionals and primary care, how would we know if a patient has PBC?

Yun Jung Kim
As a pharmacy professionals, particularly in primary care or community settings, you may not come across Primary Biliary Cholangitis for every day, but you still play a vital role in its early recognition. While you’re not expected to diagnose the condition, of being alert to potential red flags can make a real difference. For instance, if a patient has been prescribed the long term ursodeoxycholic acid, commonly abbreviated as a UDCA, and the indication isn’t clearly documented, it could point towards PBC, as a UDCA is the first line treatment. Raising this during routine medication reviews it can help ensure clarity around the treatment plans and support a continuity of care.

Other signs to look out for include persistently raised alkaline phosphatase, or ALP levels, on blood tests, or symptoms like fatigue and pruritus, especially if patients mention these unprompted. As has been discussed earlier, these are symptoms are often non-specific and may be picked up instantly during reviews for unrelated issues. Even if you are not working directly in hepatology, you are in a good position to prompt further investigation or appropriate referral. Your input, whether through identifying medication patterns, highlighting unexplained symptoms, or supporting adherence to therapy, can support earlier diagnosis, timely management and the better outcomes for people living with PBC.

Kieran Reynolds
That’s great thank you. And now you’ve already kind of mentioned this in terms of what is the first line treatment, but how is PBC treated?

Yun Jung Kim
Yes, so, the first line treatment is ursodeoxycholic acid, or UDCA, and the UDCA works by reducing the toxicity of bile acids. So, it helps to increase bile flow, reduce inflammation, and protect liver cells from further damage by reducing harmful bile acid accumulation in the liver. So, this is prescribed at dose of 13 – 15 milligrams per kilogramme per day, normally divided into two or three doses. UDCA comes in a different formulations including 150 milligrams, 250 milligrams, 300 milligrams or 500 milligrams tablets, capsules and oral suspension, which is useful for patients with swallowing difficulties or needing flexible dosing. About 60 to 70% of people with the PBC respond well to UDCA alone. For the remaining group who don’t achieve the treatment targets, meaning their blood tests haven’t improved after 12 months, then we consider second line treatments, which are usually initiated in secondary or tertiary care. There are several second line therapy options available which includes obeticholic acid, bezafibrate, and elafibranor.

Kieran Reynolds
That’s great, thank you. And can you tell me a little bit more about these second line therapies that you’ve mentioned, so obeticholic acid and elafibranor?

Yun Jung Kim
Absolutely. As I have said, the first line treatment for Primary Biliary Cholangitis is ursodeoxycholic acid. But if a UDCA isn’t effective enough or if a patient can’t tolerate it, we move on to second line options. So, one of these is obeticholic acid, or OCA. It’s a farnesoid X receptor agonist that reduces bile acid levels and improves liver function by modulating bile acid synthesis. It also has anti-inflammatory and antifibrotic properties which makes it helpful for slowing disease process. Because it’s a high-cost drug, obeticholic acid is prescribed in secondary care after a multidisciplinary team review at regional referral centres. It’s particularly considered for people who don’t respond fully to UDCA or who are UDCA intolerant.

Another second line option is elafibranor. It’s a dual Peroxisome Proliferator Activated Receptor, or PPAR, alpha and a delta agonist. So, it works by targeting both bile acid and a lipid metabolism, helping reduce inflammation and improve bile flow. NICE recently approved elafibranor for use in PBC, and it’s also reserved for secondary care and is considered in patients who don’t respond adequately to UDCA or even after trying obeticholic acid. Now, while elafibranor hasn’t been directly compared to obeticholic acid in trials, early evidence that suggests that it may be more effective at improving liver blood tests, although this comes with some uncertainty. That said, NICE concluded that cost-effectiveness falls within the acceptable range for NHS use.

Kieran Reynolds
Thank you. And you’ve also mentioned bezafibrate, which we more commonly seen being used to treat hyperlipidaemia, but does it have a role in PBC as well?

Yun Jung Kim
Yes, bezafibrate is another option, although it’s used off label in the PBC. It’s a fibric acid derivative that acts as pan-PPAR agonist, activating alpha, delta, and the gamma receptors. So, these help regulate bile acid and lipid metabolism. So, by doing so, bezafibrate can improve bile acid transport and reduce cholestasis, and ease inflammation. It’s typically used as an add-on therapy to ursodeoxycholic acid, especially in patients with an incomplete response and can be particularly useful for those dealing with the pruritus, which is a common symptom in PBC.

So, prescribers need to be aware of potential drug interactions and the renal dosing adjustments. So, for example, bezafibrate can enhance the anticoagulant effects of warfarin, so close monitoring of INR and dose adjustments are important. While initiation usually takes place in secondary care, regular monitoring such as renal function, liver blood tests, and muscle-related symptoms can often be managed safely in the primary care, provided there is good communication with the specialist team.

Kieran Reynolds
That’s great. Thank you. And interestingly, although PBC is an autoimmune condition, we don’t use immunosuppressants to treat it, it’s medicines that affect bile flow and also affect bile acid metabolism. Now you’ve mentioned OCA or obeticholic acid and elafibrinor being high-cost and hospital only medicines, but what about shared care agreements between primary and secondary care for prescribing other PBC treatments like bezafibrate that you’ve just mentioned? How do these work and what challenges or benefits do you think come with them?

Yun Jung Kim
Shared care agreements can be used when managing some PBC patients, where responsibilities for prescribing are shared between secondary care specialists and the primary care GPs. In many cases, patients being treated under the guidance of a specialist team in the hospital. Once their condition is stable, prescribing responsibility for certain medications such as bezafibrate may be transferred to their GP, depending on the local arrangements. However, not all regions have a formal shared care agreement, which can sometimes lead to GP taking on prescribing without structured support. This is particularly common in medications like also ursodeoxycholic acid, which is a frequently used as the first line therapy for PBC.

For shared care to be effective, communication between the hospital and the GP is essential. The hospital team must clearly outline the treatment plan, monitoring requirements and any potential risks, ensuring the GP is fully informed and can manage the patient effectively. Regular communication helps avoid any confusion or gaps in care, ensuring that treatments are followed appropriately, and that any necessary monitoring is done. Obeticholic acid and elafibranor are hospital only and can only be prescribed by specialist teams.

Kieran Reynolds
Thank you. And what about future treatments? Are there any coming on stream soon and how do these differ to the treatment options that we already have for PBC? Do these for example, offer any advantages over the existing therapies that you’ve spoken about?

Yun Jung Kim
Yes, there’s an exciting new treatments on the horizon called the seladelpar. It’s currently under review by NICE, with the decision expected by September this year [2025]. Seladelpar targets the PPAR-delta receptor, which plays a key role in reducing liver inflammation and fibrosis. Early studies suggest it can improve liver blood tests and slow the progression in patients who haven’t responded adequately to ursodeoxycholic acid or obeticholic acid. If approved, seladelpar could be a valuable alternative for patients with advanced PBC or those who don’t respond well to current treatments. It’s definitely one to watch, as it could expand the limited options currently available for PBC.

As we discussed before, pruritus is a major and often debilitating symptoms for PBC, alongside fatigue. A promising new class of treatment called ileal bile acid transports (IBAT inhibitors), which works by reducing bile acid reabsorption in the gut, may help tackle this problem. The first IBAT inhibitor likely to reach the market is linerixibat, which has recently been submitted for NICE appraisal, expected to start in late September [2025].

Kieran Reynolds
So that’s great. So, lots of promising treatments coming on stream for these patients. Now my next question is about how can primary care pharmacy professionals help manage these patients? We know that the diagnosis and initiation of treatment will be done in specialist centres, but what can primary care pharmacy professionals do to help provide care to these group?

Yun Jung Kim
Pharmacy professionals actually play a real important role in looking after people with PBC, especially when it comes to medicines. It’s about make sure patients are on the right of the treatments, helping them manage any side-effects and supporting them to take their medicines properly. For drugs like a bezafibrate, it’s important to keep an eye out for drug interactions and to regularly check things like renal function. We can help patients stick to their treatment plan and get the best results.

A lot of patients with PBC also deal with a symptoms like fatigue and pruritus. For pruritus medicines like cholestyramine or rifampicin can really help, and the pharmacists can guide patients on how to use these properly. But there is also lots of non-medical interventions that can make a difference, like a good sleep habit, staying active, eating well, and explaining their fatigue to friends or family so they understand. For pruritus, things like cool showers, keeping creams in the fridge using cold packs avoid scratch clothes, and wearing loose-fitting garments can all help. It’s often a bit of a trial and error to find what works best for each person.

Keeping track of how patients are doing is really important. Whether it’s checking liver, blood tests, helping promote adherence to their treatment, or spotting any drug interactions, pharmacists help keeping things on track. If patients aren’t already seeing a specialist, it might be worth talking to their GP about the referral, especially now that there are new treatments coming through. Managing PBC isn’t just about medicines, it’s about supporting the whole person, including things like bone health and the vitamin D levels. Pharmacists have a role right across all of these from reviewing medicines to speaking with the patients about their symptoms and care. And for those who work in hospital, there is even a PBC care bundle, jointly produced by the British Association for the Study of the Liver and the British Society of Gastroenterology, which can help guide the PBC treatment and prompt onwards referral when required.

Kieran Reynolds
That’s great. Thank you. And we’ll include a link to the BSG BASL PBC care bundle within the podcast blurb. Another useful resource which you can always signpost patients to is the PBC Foundation website, which is an international patient advocacy group for those living with PBC and contains lots of information about common symptoms and strategies to help deal with them.

That’s all from us here at SPS for this episode of our Liver Podcast series. Thank you for tuning in and we’ll be back with another episode soon. And thank you very much to Yun for all your contributions to today’s podcast, it’s really appreciated. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS email bulletin. This will make sure you’re always informed our most up-to-date content and you’ll receive news of upcoming events. You can also find out more about the BHPG on the BASL website or follow them on X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that all healthcare professionals are equipped to manage patients with liver disease and that they have [an] awareness of the risk factors.

My name is Kieran Reynolds and I’m an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS, and this podcast series has been co- developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals [NHS] Foundation Trust and past chair of the BHPG. This is episode seven in the liver podcast series, and we would encourage you all to listen to previous podcasts available on the SPS website.

On today’s podcast, we’re delighted to be joined by Helen, who I’ve already mentioned, is the Lead Hepatology Pharmacist at St George’s Hospital London and previous chair of the BHPG. Hello and welcome, Helen.

Helen Boothman
Thank you, Kieran. Nice to be here.

Kieran Reynolds
So, Helen, we’ve heard in previous podcasts about liver disease, cirrhosis, and in this next mini-series, we’re looking at different causes of liver disease, and today we’re focusing on hepatitis B virus. For listeners who potentially haven’t come across hepatitis B, or hep B, can you explain what it is and the incidence within the UK?

Helen Boothman
Yes, of course. First, I’ll start with hepatitis is a blanket term meaning inflammation of the liver. Hepatitis can be caused by a number of factors including viruses, alcohol and your immune system. So, hepatitis B specifically is a viral infection that affects the liver caused by the hepatitis B virus, which we also call HBV, which can lead to both acute and chronic disease. And it also has potential complications like liver cirrhosis or cancer.

The most common route of transmission is from mother to baby. But it can also be spread through poor medical practices, tattoos, piercings or injecting drugs. It can also be passed on through sex with an infected person. The hepatitis B virus can live outside the body for about a week, so it’s also possible, but not common, to get it from things like sharing toothbrushes and razors with somebody who has the virus. It’s not passed through hugging and sharing cutlery.

It’s an initially an acute infection, but 95% of children under the age of 5 [with acute infection] will go on to develop a chronic infection. However, in adults only 5% of people will go on to develop a chronic infection. This is because adults usually have a fully developed immune system which is better at fighting off the virus.

So, talk about incidence, the World Health Organisation estimates there are 254 million people living with chronic hepatitis B worldwide, with approximately 1.2 million new infections each year. The UK Health Security Agency (the UKHSA), estimate that there’s approximately 268,000 people in England living with chronic hepatitis B, that’s a prevalence of about 0.58%.

Hepatitis B is known as a silent virus, with the majority of patients having little or no symptoms when they’re infected, and this is why it’s estimated that up to 50% of people with hepatitis B in the UK and worldwide actually are unaware that they have the virus. If left untreated, hepatitis B can cause liver cirrhosis and liver cancer, and therefore early diagnosis and treatment, are vital in preventing long-term liver damage. There is a hepatitis B vaccine available and it’s highly effective in preventing infection in those at risk and in the UK all babies born after 2017 will have been offered a course of the hepatitis B vaccination.

Kieran Reynolds
And for those who are interested in learning more about the risk factors for hepatitis B infection, we will include a link to a resource to the British Liver Trust [website] within the podcast blurb. And now within this resource that we’ve linked to, I learned about hepatitis D, or delta infection. But, Helen, could you tell us more about it and what does it have to do hep B?

Helen Boothman
Of course. So, there are five main hepatitis viral infections. Hepatitis D is a virus that only occurs in patients with hepatitis B. This is because it requires the hepatitis B virus for entry into the cells and for replication. Now it’s not as common as hepatitis B, but it’s estimated that 5% of people who have hepatitis B are infected with hepatitis D, so that’s around 12 million people worldwide. It is considered to be the most severe form of viral hepatitis, and that’s due to its rapid progression to liver cirrhosis and liver cancer. There’s a drive in the UK to ensure that all patients with hepatitis B have been tested for hepatitis D so we’re aware. The roots of transmission for hepatitis D are the same for hepatitis B, and the hepatitis B vaccination effectively prevents hepatitis D infection.

Kieran Reynolds
That’s great, thank you. Now, my next question is how are hepatitis B and D diagnosed?

Helen Boothman
OK, so as I mentioned, hepatitis B is what we refer to as a silent virus, as the majority of people infected don’t experience any symptoms and that’s in either the acute or the chronic phase of the infection. Often people may get generalised symptoms like flu-like symptoms, but not necessarily. So, we use blood tests to diagnose hepatitis B and D. Unfortunately, they’re not routinely tested for in the UK, apart from in certain situations, such as antenatal testing, and now we have opt out testing in some of our emergency departments across the country.

Hepatitis B is a complicated infection, and we do a number of blood tests to confirm the infection. So, we look out for a positive hepatitis B surface antigen, and this indicates a current infection, and then we’d go on to check viral load, which is also known as hepatitis B DNA levels, and this helps us to see how active the virus is. As we mentioned earlier, some people clear hepatitis B, especially as adults. However, unfortunately it’s a really clever virus that enters the liver cells and integrates with the cccDNA, meaning that it’s almost impossible to get rid of. This means that although people clear the virus, there’s a possibility that it can reactivate if the body’s immune system is suppressed. We look for this in a blood test and people who have previously cleared the virus will be positive for hepatitis B core antibodies.

Just a little bit about hepatitis B reactivation, it’s normally due to certain immunosuppressant medicines, for example chemotherapy. But it can be prevented by using antiviral prophylaxis with medicines such as entecavir or tenofovir, which we’ll talk about. It is important that previous hepatitis B infection is tested for in patients who are undergoing immunosuppressant therapy to prevent reactivation, as reactivation of hepatitis B can result in acute liver failure and death.

The tests involved in hepatitis B testing are quite complex and we don’t have time on this podcast to discuss them all, and I think it’s very difficult for us to give a summary. But to recap, the most frequently seen of these tests are: hepatitis B surface antigen, also [known as] hepatitis BsAg. If this test is positive, it indicates a person has chronic hepatitis B infection. We’ve also got hepatitis B DNA, or viral load. This measures how much hepatitis B is in the blood and how active the virus is. And last but not least, hepatitis B core antibody. So, this is [the] antibody against the core antigen, and if this test is positive and the hepatitis B surface antigen and viral load are negative, it may indicate that the patient has had a previous, or cleared, hepatitis B infection and therefore has potential risk of reactivation.

Kieran Reynolds
So, as Helen has mentioned, the tests involved in testing for hepatitis B are quite complex, and if you’re interested in learning more about the diagnosis of hepatitis B infection, we will include links to resources from the British Liver Trust and also NICE CKS within the podcast blurb.

Now, many people may not know this, but the World Health Organisation, or the WHO, have a target for the elimination of viral hepatitis, which includes both hepatitis B and hepatitis B, C, excuse me, by 2030. We’ll hear on our hepatitis C podcast about progress towards hepatitis C elimination, but how will this happen for hepatitis B?

Helen Boothman
So, unfortunately for hepatitis B, there’s currently no cure, but there is antiviral treatment available to suppress the virus and reduce the risk of progression to liver damage and liver cancer. As I’ve already mentioned, there is an effective vaccine available and this is now included in the childhood vaccination schedule in many countries worldwide, including the UK. Health workers and people who inject drugs are also offered the vaccine. And it’s often recommended for travel to certain countries. However, there are difficulties with this vaccine, as it must be given as 3 injections over six months, which means it’s often not completed.

Achieving hepatitis B elimination will require a multi-pronged public health effort and this includes: universal hepatitis B vaccine, prevention of mother to child transmission, which the UK are doing very well at at the moment, improved and increased testing and diagnosis, which we’ll talk about a little bit [later], expanding and improving access to treatment, investing in strengthening public health infrastructure, and a lot of community engagement and education with both healthcare professionals and patients to overcome stigma and improve awareness. So hopefully this podcast will help towards that.

Kieran Reynolds
That’s great, thank you. And you’ve briefly mentioned it previously, but speaking of specific hepatitis B and D treatment, can you give us more information about this?

Helen Boothman
Yeah, so, there’s no cure, like I said, but antiviral treatment helps to reduce liver damage, suppress the virus and prevent complications like cirrhosis or liver cancer, which is really important because hepatitis B is known as what we call an oncogenic virus, so can cause liver cancer. However, not everyone with hepatitis B needs treatment, and the decision to start treatment will be made by a specialist and will depend on a few factors, including viral load, liver enzyme levels, and amount of liver damage, if any is present, as well as other factors including comorbidities for liver damage, and family history of liver cancer is a big indicator for treatments.

People with liver damage, and I know we’ve discussed that on previous podcasts, active liver inflammation or high hepatitis B DNA levels are typically treated with antiviral medications. In the UK, these are tenofovir disoproxil or entecavir. Those with no liver damage, normal liver enzymes, and low viral loads are often monitored rather than treated, with blood tests and scans. Often treatment is now generally life long and monitoring is essential for patients living with hepatitis B. The recent European Association for the Study of the Liver (the EASL) guidelines, they were updated for hepatitis B treatment, and this has actually made hepatitis B treatment more available to people. They’ve lowered the thresholds, particularly those in the early stages of liver disease, who would previously been monitored rather than treated. This means that more patients will be treated rather than monitored, which will cause an increased demand on outpatient liver services. And now I’m not sure if you’re aware, but pharmacists are actually key to managing these patients and we have a number of pharmacist-led hepatitis B clinics across the country.

For hepatitis D, for years the only treatment for hepatitis D was a course of pegylated interferon, which is off-label. But in 2023, bulevirtide was approved by NICE for the treatment of hepatitis D for people who have significant fibrosis or have failed to respond to pegylated interferon or if they can’t tolerate it. Bulevirtide is a once daily injection that patients have to reconstitute and draw up themselves, and it’s currently a long-term or lifelong medicine, so not suitable for everyone.

Kieran Reynolds
And for those who are keen on learning more about hepatitis B treatment, the British Liver Trust have an excellent resource which we will again link to within the podcast blurb.

Now, Helen, you mentioned about current treatments, but what about potential future treatments for hepatitis B? Are there any coming on stream soon and how do they differ the treatment options that we already have?

Helen Boothman
So, the EASL guidelines have now included future treatments which actually look towards achieving a functional cure. This means the virus becomes undetectable and the hepatitis B surface antigen clears from the blood. This leads to long-term virus control without ongoing treatment. It’s rare with current therapies, for example, tenofovir, entecavir or pegylated interferon, but it’s a key goal for treatments currently undergoing investigation. There are some promising treatments in development and early clinical trials shows encouraging results, especially in combination therapies, but larger clinical trials are ongoing to confirm their effectiveness.

Kieran Reynolds
That’s great, thank you. Now we hear a lot in the media about increased HIV testing in emergency departments [ED] around the country, but does this also include hepatitis B testing?

Helen Boothman
Yes, I’m glad you mentioned that. So, there are a number of emergency departments in England where opt out testing occurs and it’s a great initiative. So, any patient over the age of 16 who is having a blood test in the emergency department will have hepatitis B, C and HIV added on, unless they opt out of this testing. There have been some reports on it already. So, a report from the UKHSA evaluating the first 24 months of testing in 21 of the emergency departments showed that nearly 2,000 people were diagnosed with hepatitis B, and this number continues to increase with increasing testing. This is in addition to the increased treatment required following the EASL guideline recommendation, which means there is again an further increase in demand on the hepatology services and hospitals across the country are struggling to deal with these, so new models of care will have to be designed, and I think pharmacists stand in a great position now and [will be] essential to these new models.

Kieran Reynolds
So, lots of change coming. Now we’ve heard a lot in recent months about the government’s big shifts for the NHS. How does the future of hepatitis B care fit in with these 3 shifts?

Helen Boothman
I hope hepatitis B care aligns with these government key NHS shifts in terms of the treatment to prevention. We are seeing earlier diagnosis with the rollout of ED opt out testing and this is leading to earlier treatment initiation and prevention of worsening liver damage and preventing liver cancer. Also, with a bigger awareness and the increasing vaccinations, hopefully we can move this to prevention rather than the necessity of treatment.

In terms of the hospital to community shift, hepatitis B is generally managed in secondary care, but there is work ongoing to transition into the community. There’s also a number of recently launched initiatives tasked with identifying patients with cirrhosis earlier on in the community. These include the NHS England Community Liver health pilots and also the inclusion of FibroScans which can detect liver fibrosis and cirrhosis being included in the community diagnostic centres or referral from direct from GPs.

Kieran Reynolds
That’s great, thank you. And of course, numerous initiatives will also align with the [analogue to] digital shift.

Now, finally, Helen, how can primary care pharmacy professionals help manage these patients? And do you have any hints or tips for them?

Helen Boothman
Yeah, I think pharmacy definitely can, they can contribute a lot to these patients. Unfortunately, the antiviral treatments are currently hospital only medicines and the opportunity for shared care with primary care is difficult. However, there may be opportunities for those patients who just require monitoring [to] have arrangements with primary care as we move further into these pathways, these new novel pathways for treatment or monitoring. There’s ongoing work to look at establishing more clinics within community and this will hopefully help to reduce the attrition rate to treatment and monitoring the patients and ensure they remain in care.

Primary care pharmacy professionals are also well placed, and community professionals, at identifying potentially the risk of hepatitis B and D and ensuring that patients are tested and referred, or tested or referred for testing within their GP. We know that up to 50% of people with hepatitis B in the UK are unaware that they have the virus and as we progress towards viral hepatitis elimination, we need to find these people and ensure they are linked into appropriate care. So, this includes people coming from certain high prevalence areas and those with the risk factors that we discussed at the beginning. And unfortunately, there’s a huge amount of stigma associated with hepatitis B infection, and this often stems from misconceptions about transmission and association with drug use or sexual activity. But the stigma often differs depending on which community groups they’re in, and it can lead to isolation and delay for patients accessing care and also reduced amount of people being tested, contact testing. Support groups like the Hepatitis B Foundation, the British Liver Trust and the newly formed Hepatitis B Companion provide patient education, peer support and advocacy to reduce stigma and improve patient well-being. Pharmacy care professionals can also signpost patients to these groups and their resources, which I think we’ll include in the podcast blurb.

Kieran Reynolds
Absolutely we will.

Now, that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon. And thank you, Helen, for all your contributions to today’s podcasts and all the previous podcasts. We’re always keen to hear from you about suggestions you have for our resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up-to-date content, and you will receive news of upcoming events. You can also find out more about the BHPG on the BASL website or follow them on X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service [SPS] in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing, and it is important that all healthcare professionals are equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds and I’m an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co- developed with Helen Boothman, lead Hepatology pharmacist at St George’s University Hospitals [NHS] Foundation Trust and past chair of the BHPG.

This is episode eight in the liver podcast series, and we would encourage you all to listen to previous episodes available on the SPS website. On today’s podcast, we are delighted to be joined by Helen Boothman, who has co-developed this series. Hello, and welcome to you, Helen.

Helen Boothman
Hi, thank you, Kieran.

Kieran Reynolds
So, Helen, we’ve heard in previous podcasts about liver disease, cirrhosis, and in this next series, we’re discussing different causes of liver disease, the focus of today’s podcast being about hepatitis C [hep C] virus. For listeners who maybe haven’t come across hep C before, can you explain what it is?

Helen Boothman
Yes, of course. So, if you have listened to the hepatitis B podcasts then you’ll know that hepatitis is a blanket term that means inflammation of the liver. Hepatitis can be caused by a number of factors, including alcohol, your immune system and viruses, which we’re going to talk about today.

So, hepatitis C virus is one of five main hepatitis viruses that affects the liver and if left untreated, can cause liver damage and liver cancer. Hepatitis C is transmitted as a blood-to-blood infection, and the most common route of transmission in the UK is from injecting drug use. This is mainly through sharing needles and drug equipment, and that can include the water with an infected person, but this is not the only route. It can also be spread through inadequately sterilised tattoos and piercing equipment, infected blood products, sexual contact with an infected person, or poor medical practices, for example, vaccinations and dental work with inadequately sterilised equipment. Being born in a country with high hepatitis C prevalence, including some countries in Southeast Asia or Eastern Europe also increases your risk of being infected.

You may or may not have heard of more recently of the UK Infected Blood Inquiry and that investigated how thousands of people were infected with HIV and hepatitis through contaminated blood products in the 1970s to 1990s. This inquiry revealed systematic failures by the NHS and government, including delays in withdrawing unsafe products and a lack of transparency. All blood and blood products donated in the UK are now screened for hepatitis C and other blood borne viruses to remove this risk. But we are still finding patients who are maybe being infected through this route. The hepatitis C virus can also live outside the body in this time for several weeks, so it’s possible but not common again, to get it from sharing things like toothbrushes and razors with somebody who is infected. Hepatitis C typically presents as an acute infection with approximately 30% of individuals spontaneously clearing the virus, and the rest go on past six months to have a chronic virus.

Kieran Reynolds
That’s great. So, now we know about the risk factors, but what is the incidence of hepatitis C?

Helen Boothman
So, the incidence varies across the world, but globally an estimated 50 million people have chronic hepatitis C virus with about 1 million new infections occurring per year. These figures are based on modelling and that’s because like hepatitis B, hepatitis C is also known as a silent virus, with the majority of patients having little or no symptoms when they are infected, and this is why it’s estimated up to 50% of people with hepatitis C are unaware that they have the virus.

NHS England for the past number of years have invested significant resource improving awareness of hepatitis C and the risk factors associated with it to try and drive testing and diagnose more patients. They promote testing of those individuals at risk of infection. This is because without finding patients who are infected and treating them, we risk the infection spreading to others.

Kieran Reynolds
That’s great, thank you. Now, if you’ve listened to our hep B podcast, you will already know this, but the World Health Organisation (or the WHO) have a target for the elimination of viral hepatitis, which includes both hepatitis B and C by 2030. Now we’ve heard in the hep B podcast about the changes required to achieve hep B elimination, but can you give us a little insight into the progress made towards hep C elimination?

Helen Boothman
Yes, of course. Slightly easier than the hepatitis B path, but in 2016 the new Direct Acting Antiviral medicines, or DAAs, as we hear them called, offered a cure for hepatitis C, this is with a high success rate of around 95%, and this gave us a real opportunity for elimination of the virus. This is an incredibly high cure rate, especially when compared to other diseases, many of which have no cure. So, since the discovery of the hepatitis C virus in 1989, the development of an effective cure within just 30 years stands as a testament to the extraordinary progress of scientific research and medical innovation.

To help deliver the rollout of these treatments, NHS England established operational delivery networks, or ODNs for short, which you may have heard of, and this is a specialist hub hospital which supports a number of spoke hospitals in their local area. The ODNs have transformed the delivery of hepatitis C services across England, improving access to specialist care and treatment with a move from hospital to community-based care, with increased access to care and treatment in non-traditional clinic environments including drug services, hostels, and more recently community vans. DAAs are expensive, and in fact at one point they were the highest costing medicines in the world. NHS England actually mandated that a pharmacist be included in the MDT [multidisciplinary team], which is a great opportunity for pharmacy, and initially the role was to promote and ensure financial governance arrangements were in place and adhered to, and to also ensure there were no significant drug-drug interactions with the earlier DAAs. Since then, the role has evolved, and many pharmacists are now embedded as key members of the ODNs in their hospital, ensuring timely and appropriate access to specialist medicines.

My role as a pharmacist within the ODN has also changed, helping me take on more of a project management role and service delivery rather than just traditional pharmacist roles alongside outpatient clinics. NHS England also have a commercial agreement now with three of the pharmaceutical companies making the DAAs, and this included accessing medicines at a price point that the NHS can afford. But also, alongside this, helping to find undiagnosed patients. This has involved working with drug and alcohol services, prisons and GP surgeries to help identify patients with the virus so they could be treated. It does represent a success story as the entire programme of work has resulted in around 100,000 hep C treatments being started since 2015, with a 57% reduction in the prevalence of hepatitis C and this has been associated with a reduction in hepatitis C related mortality and a reduction in the number of [liver] transplants that are needed due to hepatitis C, which is great news.

Kieran Reynolds
Indeed, great news and really significant progress made. Now, Helen, can you give us some information about how pharmacy teams that don’t directly work within hepatology can help identify patients with risk factors for chronic hep C infection?

Helen Boothman
Yeah, I think they offer a real opportunity for diagnosing more patients, especially community pharmacies and primary care pharmacists who are working more closely with a lot of patients. As many people will be unaware they have the virus and it’s silent, so many people are not having any symptoms in the earlier stages of the virus. There’s generalised symptoms including fever, we often hear fatigue or people feeling very tired, and loss of appetite. Testing is not routinely performed, but the ODNs alongside NHS England have driven for more testing and now there’s opt out testing for hepatitis C, hepatitis B and HIV in a number of emergency departments across the country, and routine testing in drug services and prisons. But there could be an increased testing in primary care, and because of the lack of this testing routinely, it’s important to identify patients with risk factors so they can be tested. So, like we said earlier, these risk factors include people born in high prevalence countries, people who previously or currently inject drugs, and blood transfusions received prior to 1994.

So, if you work in a GP practice and identify somebody with these risk factors, we’d advise you check the patient’s hepatitis C status, if they’ve had a test and if they know about their status. There is a lack of awareness of the new treatments for many people. So, many people still think it’s older treatments like pegylated interferon, which had a lot of intolerable side effects. So, this then unfortunately means there’s a number of people who were diagnosed a number of years ago and have remained untreated but are not aware that they can actually have these oral treatments now.

There are also a number of GP Champions across the country who take an active role in raising awareness of hepatitis C in primary care and help finding cases of hepatitis C. They work closely with the ODNs to help facilitate this, and actually if you work in a GP practice or are interested, you can work with your local ODN to run a search of people with risk factors, or with previously positive hepatitis C result. These searches are available on the electronic health records in primary care, for example EMIS and SystmOne.

Kieran Reynolds
That’s great, Helen. And now can you give us a little bit of information about how hepatitis C is diagnosed?

Helen Boothman
Of course, yeah, all this information about testing, but not actually how it’s diagnosed. So, it is a blood test. So, two different blood tests are needed to diagnose hepatitis C. Initially, a hepatitis C antibody will be tested, which indicates a current or previous infection. Then you do a hepatitis C RNA or viral load, and this confirms if the infection is active and needs treating. It’s important to note that when people are treated and clear hepatitis C, they will continue to have a positive hepatitis C antibody, but this does not mean that they have the active virus, and they are not at risk of reactivation like hepatitis B. Once patients are cured of hepatitis C, they can become reinfected, so, if they are re-exposed to a risk, they need to be re-tested. Unfortunately, there’s a lot of stigma associated with hepatitis C, and many patients with risk factors may not disclose them and therefore may not come forward for testing. Patients can request a free confidential at home testing kit for hepatitis C as long as they’re over 18 years of age and with an address in England, and this offers private discreet way to get tested as the results are sent directly to them.

Kieran Reynolds
That’s great, thank you, and we will include a link to this service [Free at home NHS hepatitis C test] within the podcast blurb.

Now, Helen, you’ve mentioned the DAAs being key treatments for hepatitis C, but can you give us a little bit more information about how the different treatments are decided for each patient?

Helen Boothman
Yeah, so, as I mentioned, the cure for hepatitis C is up to 95% effective. The Direct Acting Antivirals (or DAAs) are combinations of two or three different drugs in an oral tablet and this needs to be taken for between 8 to 12 weeks deciding on certain factors. So, treatment is decided using genotype. So, hepatitis C has seven different genotypes. Knowing the genotype helps to decide on the best course of treatment as some are genotype specific and others are pan-genotypic. The stage of liver disease, so patients with cirrhosis can be more difficult to treat so it’s important that we know this, they may need a longer course. Medication history to look for [drug-drug] interactions; although the new DAAs still have minimal significant drug interactions, it’s still important that they are considered. And also previous treatment of hepatitis C as this can result in resistance to some of the treatments.

In addition to this, NHS England produce a rate card to advise which treatments can be used, and the proportion that we should aim for to ensure that the commercial agreement they have with the pharmaceutical companies is upheld. Treatment is provided by ODNs in a number of different locations, like we said, including outreach, so, drug and alcohol services, prisons, community vans and in some cases, homeless hostels, and there have been incidences of community pharmacies providing the medicines.

Treatment is generally very well tolerated and some patients reporting mild to moderate headache or fatigue, and it can be reassured that those side effects are generally mild to moderate in severity and usually go away very quickly. There’s very limited times we’ve had to change patients because of side effects.

Patients are tested during treatment, depending on which location they’re being tested in, but 12 weeks after a patient finishes treatment, we will re-test them for the hepatitis C virus viral load, and if this is negative then they have achieved what we call a sustained virological response at 12 weeks, also known as SVR12. This means they’ve cleared the infection. And like I said earlier, will remain hepatitis C antibody positive, but it’s really important that primary care records are updated to show this.

After treatment, some patients will need longer term care, those patients with advanced fibrosis or cirrhosis, and this is to monitor their liver, and they may need hepatoma surveillance. But for the majority of patients, they can be discharged once they’ve cleared the virus.

So, as I mentioned, there is a lot of stigma associated with hepatitis C and this also happens between healthcare professionals who maybe have misconceptions about transmission and the association of [with] drug use. It’s really important that healthcare professionals with patient contact understand the risk factors and know that once cured, they won’t transmit hepatitis C but also knowing where to signpost patients to, if they do have an active virus. Now more than ever, it’s important to make every contact count.

Kieran Reynolds
That’s great, thank you, Helen. Now you’ve mentioned increased case finding earlier, but can you give us some information to our listeners about how this happens in practice?

Helen Boothman
Of course. So, like I said, there’s about 50% of patients who are undiagnosed or unaware of their virus. So, some of the initiatives focus on testing in populations of people with risk factors. This includes people who inject drugs, people who may be homeless, and migrants from high prevalence countries, and also testing in prisons. NHS England, in collaboration with the hepatitis C Trust, which is a patient advocacy group, have trained and employed a number of peer support workers and often these are people who have lived experience of hepatitis C and they often support testing initiatives and can support patients throughout their treatment and can also raise awareness. But this has made a significant difference in difficult to engage patient groups, ensuring that they complete their treatment, giving them the best chance of achieving a cure, but also reducing the stigma around it. There’s also been significant investment in point of care testing, ensuring rapid diagnosis of hepatitis C, and this includes finger prick testing and a Cepheid machine. This helps to shorten the path between diagnosis and treatment, supporting a test and treat pathway.

Opt out testing in prisons and EDs has also identified a number of patients as have test and treat initiatives in prisons, which they try to test the whole of the prison in one go and treat as quickly as possible. It allows patients to complete their treatment while in prison or be followed up in the community with the hepatitis C Trust peers, if necessary. Collaboration with a number of third sector and community organisations has also helped reach vulnerable groups, organise testing events and provide peer support.

Kieran Reynolds
That’s great, and are there any other initiatives being undertaken by the NHS to try and identify liver disease or identify those patients at risk of liver disease?

Helen Boothman
Yes, I think now more than ever there’s greater emphasis on prevention and reduction of risk factors as we’ve seen from the NHS aims. And we’ve mentioned in some of these previous podcasts, but there are a number of recently launched initiatives tasked with identifying patients with liver disease earlier or those with risk factors earlier on, and these include the Community Liver Health Pilot, which involves testing patients with risk factors for cirrhosis. It also includes direct access to FibroScans from GP surgeries in community diagnostic centres across the country, and that’s just to name a couple.

Kieran Reynolds
That’s great, thank you.

Now that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon. And thank you to Helen for all her contributions to today’s podcast and the previous podcasts. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our up-to-date content, and you’ll receive news of upcoming events. You can also find more about the BHPG on the BASL website or follow them on X at @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy service. Thank you and bye bye for now.

Kieran Reynolds
Hello and welcome to our liver podcast series from the NHS Specialist Pharmacy Service (SPS) in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing and it is important that healthcare professionals are all equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds, and I am an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co-developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s University Hospitals [NHS] Foundation Trust and past chair of the BHPG.

This is the episode nine in the liver podcast series and we would encourage you all to listen to the previous podcasts available on the SPS website. On today’s podcast, we’re delighted to be joined by Leslie Wong, Advanced Clinical Pharmacist in hepatology at the Eastern Liver Network and Communications officer at the BHPG. Hello and welcome Leslie.

Leslie Wong
Hello Kieran. Thank you for your invitation.

Kieran Reynolds
So, Leslie, we’ve heard in previous podcasts about liver disease, cirrhosis and in this next series looking at different causes of liver disease, and today our focus is about alcohol related liver disease or ARLD for short. For our listeners who aren’t familiar with this term, could you help explain what it is and give a little bit of an insight into the incidence within the UK.

Leslie Wong
No problem. So, alcohol related liver disease, or ARLD for short, is a condition where the liver has been damaged by alcohol, and there are two ways alcohol misuse or drinking too much alcohol can cause ARLD. These are drinking a large amount of alcohol for a short period of time, like binge drinking, or drinking more than the recommended limits of alcohol over many years. But it’s important to also know that you don’t have to show signs of addiction or dependence to be affected by ARLD. Just having a half a bottle of wine or a few pints or more than the recommended amount for most evenings can still damage your liver.

Drinking alcohol on top of other liver conditions can also compound the damage and make the liver disease worse. If you drink too much alcohol on top of any of these, your chance of developing alcohol related liver disease is greater. These risk factors are: being overweight, having diabetes, if you’re female, or have any pre-existing liver conditions such as viral hepatitis or hemochromatosis.

So, the government have safe drinking limits recommended for all of us. It’s the same for men and women and they are: no more than 14 units a week and spread out over several days, and we would like to have two to three days without alcohol every week. It’s best if those days that you don’t drink are next to each other. And I always try to think of units as, you know, one shot of spirit (25mL) as one unit, a glass of wine is about two units, and a small bottle of beer is one and a half to two units.

If patients regularly drink alcohol to excess, they should speak to their GP so they can check if the liver is damaged and us as pharmacists, we can also help by signposting patients to services if they identify alcohol misuse. We are also seeing some patients being referred to community diagnostic centres for investigation of their liver disease due to alcohol misuse [and] being diagnosed with fibrosis or cirrhosis. Back to you.

Kieran Reynolds
That’s great, thank you. And further information can be found on the British Liver Trust website, and we will include links to these resources within the podcast blurb.

Now Leslie in terms of prevalence, how common is ARLD?

Leslie Wong
So, it’s a really big problem in the UK. It’s one of the leading causes of liver disease, and liver disease by itself is rising over the years. It’s the only major health problem that has an increasing incidence and alcohol related liver disease is accountable 60% of all liver related deaths and they have been increasing over time, especially following COVID. And people reported drinking more heavily after COVID as well. It’s a major cause of hospital admissions and thousands of people are admitted annually to hospital because of alcohol related liver conditions.

Deaths due to alcohol is rising with over 10,000 people dying from alcohol related causes in 2022. Three quarters of these deaths were related to alcohol related liver disease, a 30% increase since 2019, and almost a 50% increase since 2012. You know, these figures are showing significantly higher mortality rates in the North East, North West, Yorkshire and the Humber and this also highlights the localised impact of alcohol harm within communities across the UK.

Kieran Reynolds
So now we know how prevalent it is, my next question is, how is ARLD diagnosed?

Leslie Wong
Yeah, so similar to other types of liver disease, you know, alcohol related liver disease doesn’t usually cause any symptoms until the end where it [the liver] has been permanently and severely damaged, we call that cirrhosis, and it is often first suspected when tests for other medical conditions show a damaged liver. This is part of the reason why it’s been hard to catch. And similar to diagnosing other types of liver disease, alcohol related liver disease is diagnosed by a combination of blood tests, scans, and potentially a camera test (called an endoscopy), and liver biopsy. And you can see these diagnoses are not simple and they require multiple layers of testing, blood, and imaging before you can reach a diagnosis.

So, we have screening tools such as the AUDIT tool, which is the Alcohol Use Disorder Identification Test. This can be used to assess the nature and intensity of alcohol misuse. The questions there are quite, just asking about, how much you’re using and it relies on the patient being honest here. And other screening tools such as AUDIT-C questionnaire can be useful where time is limited. You know, we have really good organisations now across the UK helping. An organisation called DrinkAware has also developed a self-assessment tool which is available online based on the AUDIT-C tool for patients and their families to help determine their risks of alcohol related problems, outside of a clinic setting. And this DrinkAware drinking check asks you some background questions like your age, your sex, and if you’ve done an assessment like this before, and then it asks specific questions about your drinking habits, like how often do you drink? How many units of alcohol do you drink on the typical day? And how often you drink eight or more units on one occasion. It then calculates your risk of alcohol related health problems: low, increasing, high or possible dependence and it gives you tips on how to help reduce your drinking and signposting to other services, ([the] DrinkAware [website] itself will have resources there), but it just helps people to identify problems and maybe escalate and seek help if they find they have increased risk of alcohol related liver disease.

Kieran Reynolds
That’s great and we’ll of course include a link to those resources within the podcast blurb again.

Now in recent years we’ve seen a huge increase in the popularity of both low and no alcohol drinks. Are these potentially appropriate substitutes for those who want to cut down on their drinking?

Leslie Wong
So yeah, DrinkAware has produced really useful guidance for people on how to cut down on their drinking, including guidance on low and alcohol-free drinks. It really has become popular in the last one or two years and we see them, you know, being advertised during dry January by supermarkets as well. So, these options can serve as an appropriate substitute for those looking to cut back on their alcohol substitution, helping to support healthier habits while still allowing social participation, because a lot of people they like going to the pub and seeing their friends and they feel like they have to drink, but if there are alcohol-free products available, they can still have their social participation but cut down on alcohol intake and this has proven to be useful for these people. But it’s important to know that low-alcohol and even marketed as alcohol-free drinks aren’t truly 0% alcohol and they’re not suitable for everyone. They may not be acceptable if you need to completely avoid alcohol for religious reasons and they aren’t recommended for anyone who’s pregnant, dependent on alcohol, or under 18 years old.

Kieran Reynolds
And we will include a resource, again, to these resources from DrinkAware within the podcast blurb.

So, the message is clear then, Leslie, if you drink regularly to excess, which is above the recommended amounts recommended by the government, you should speak to your GP about getting your liver checked for potential liver damage. So, my next question is, how is ARLD treated, and is it just as simple as not drinking anymore?

Leslie Wong
Well, certainly, you know the main treatment is to stop drinking, preferably for the rest of your life, because this stops further damage to your liver, and stopping drinking is the only way to stop further damage and progression of your liver disease and in some cases it can reverse it, but only if it’s caught early. Stopping drinking isn’t easy, because especially when about 70% of people with alcoholic related liver disease are dependent on alcohol. And if a person is dependent on alcohol, stopping drinking can be very difficult. Patients may need support with addiction services, mental health services, and social issues sorted, and this requires a multi-disciplinary approach to it. Within a hospital setting, you will often see alcohol dependents [patients] who are admitted for other medical reasons, who undergo medically assisted alcohol withdrawal. While in hospital, and not drinking, you know, people can have acute alcohol withdrawal and [are] at high risk of alcohol withdrawal seizures or even delirium. So, these medically assisted alcohol withdrawal programs aim to reduce the risk. And yeah, it’s quite common for us to see these patients and they’re on these CIWA-Ar [Clinical Institute Withdrawal Assessment for Alcohol, revised] protocols and it involves treating symptoms of acute alcohol withdrawal, generally with long acting benzodiazepine like chlordiazepoxide, lorazepam, and those who are also at risk of developing or suspected with Wernicke’s encephalopathy, should be offered these drugs and also thiamine replacement because it is the lack of thiamine that causes Wernicke’s encephalopathy. And this is typically used to be given in the form of parenteral IV Pabrinex but there was a shortage, and the product got discontinued, so the whole country’s now switched to IV thiamine, which is more generic and used globally.

Kieran Reynolds
That’s great. And for more information about potential medicine supply issues, you can always register for access to the SPS shortages tool, but to make sure that you have an NHS email address in order to be able to register for this.

Leslie Wong
So, back to the sort of acute alcohol withdrawal protocols, the benzodiazepine dosing, chlordiazepoxide particularly is typically based on the severity of alcohol withdrawal symptoms. And, you know, the most common tool is the CIWA-Ar score, and the approach is, you know, used in inpatient and community settings based on clinical risk. The CIWA is basically assessing what symptoms the patients are experiencing and how frequently that they are experiencing it, and the higher the score, the more likely they will need another dose of chlordiazepoxide being given. And this is why close monitoring is essential to manage the side effects to support a safe, gradual withdrawal from alcohol. I’m sure all of, locally, all the hospitals will have their own protocols, so just refer to that. And one of the important notes here is that patients typically shouldn’t be discharged on these benzodiazepine because the active metabolites of chlordiazepoxide have long half-lives, so patients will still have some in their system for days after they complete their course.

Long term thiamine supplementation will be indicated for the prevention of Wernicke’s, often in the form of tablets, but to note that vitamin B compound strong tablets are no longer recommended because there’s not enough evidence to support use for acute alcohol withdrawal. You still see patients prescribed, especially in the community, it’s an opportunity there to deprescribe and review the indication. For our hospital, we are now only using it for short-term for use in refeeding syndrome and we’ve stopped ever discharging people on it long-term. Now thiamine does have lots of evidence behind it, so we use the oral tablets, 100mg three times a day, to increase the absorption spread it out throughout the day, but often times patients may struggle with a three times daily regimen so a practical way to do it is 300mg once a day. There’s lots of debate on how long thiamine should be continued for. Each patient should be assessed on a case-by-case basis, but generally it is left on the repeat prescription for them to take long-term. A general rule is, you know, they should be continued for four to six weeks and if the patient is no longer drinking and is eating well, then the thiamine can be stopped. For patients who continue to drink or have ongoing poor nutrition, then the thiamine should likely be continued potentially indefinitely. That was what I was mentioning because obviously in a big liver ward, probably those are the patients that we see most often.

Kieran Reynolds
For more information on the use of thiamine and alcohol dependence, SPS have published a resource on using and prescribing thiamine in alcohol dependence. And for more information about the use of vitamin B co strong and the lack of evidence supports its use in these patients will also include a link to the regional medicine’s optimisation committee or RMOC position statement on its use.

Leslie Wong
Thank you. So, for longer term care, you know, generally as an outpatient and primary care for alcohol related liver disease, it really is, you have to take a multidisciplinary approach because it involves the liver team, the GP, addiction services, the dietician, and social support with individuals providing, you know, them support for alcohol dependency and also providing liver care. The patient’s engagement in this is very important and they can include blood tests, managing the complication[s] of cirrhosis (if they already are at that stage), like portal hypertension or [hepatic] encephalopathy, having cancer surveillance for HCC [hepatocellular carcinoma] and people with cirrhosis giving nutritional support, ensuring that their food intake and nutritional intake as well so they can gain what they lost. And if appropriate and the liver disease is very severe, then they might get referred for a [liver] transplant too.

And alcohol dependency support may include referral to these alcohol support services, drug and alcohol services, addiction services or providing medicines to support abstinence, things like acamprosate, disulfiram, naltrexone, baclofen, which we’ll talk about in detail later. And you know these medicines have shared care agreements in place in some areas, so some GPs maybe able to take on prescribing responsibility with or without a shared care agreement depending on where you are.

So recently, the NHS ten-year plan came out and we’ve heard a lot about these three big NHS shifts in the long term to help improve efficiency and patient outcomes. They are: sickness to prevention, moving hospital care from hospital to community, and moving from analogue to digital. Now in terms of managing alcohol related liver disease, we may see a greater focus on preventing alcohol misuse and alcohol related liver disease in general, through public health measures like increasing awareness of the risks and implementing policies that address the affordability, promotion, and availability of alcohol to reduce its detrimental impact. And we may also see more non-complex alcohol related liver disease patients in the community where more care being provided to these patients in the GP setting rather than hospital setting.

Kieran Reynolds
That’s great, and for more information on the management of cirrhosis, you can always have a listen back to our cirrhosis podcast within this series.

Now Leslie, you’ve mentioned previously some of the treatments or medicines that are available for supporting abstinence. And can you tell us a little bit more about these and potentially how they’re used in practice?

Leslie Wong
Of course, there are national guidelines on this. So, NICE have guidance that recommends acamprosate as the first-line option to help maintain abstinence in people with moderate to severe alcohol dependence. It helps by reduce[ing] cravings and has been shown to increase abstinence, particularly when started after detox, which is why we see it so much in the hospital when discharging patients. But it has not been studied in patients with severe liver cirrhosis and if [you] know the Child Pugh score [system], it’s Child Pugh score C.

Another drug, an alternative to acamprosate is naltrexone, particularly in cases when acamprosate is not suitable, like if the patient doesn’t tolerate [it], it hasn’t worked, or they have renal impairment. Similar to acamprosate, it should be started as soon as possible after abstinence is achieved and it helps reduce relapse by blocking the rewarding effects of alcohol in the brain and may be especially helpful for patients struggling with cravings, lapses or binge drinking. It is less effective at achieving full abstinence and is cautioned in liver impairment so monitoring of LFTs [liver Function fests] may be required.

Another older drug is also recommended by NICE is disulfiram, and now it’s used when acamprosate and naltrexone aren’t suitable. But you need to counsel patients on how it works, what the disulfiram like side effects are if you drink alcohol and have disulfiram at the same time, and they also have to be aware of the rare complication of hepatotoxicity and [the] importance of seeking urgent medical attention if they become unwell or develop a fever or jaundice.

And finally, baclofen, which isn’t included as an option in the NICE guidelines, but there is increasing evidence for its use and should be only considered in specialist cases. There’s mixed evidence with somewhat inconsistent study results in treating alcohol dependence. So, due to the potential side effects such as sedation, dizziness, and risk of overdose, it’s not really routinely used in common practice but more in specialist settings when all other options have been exhausted.

The decision to which treatment should be offered depends on the individual patient factors like liver/kidney function, treatment goals, whether we’re trying to reduce alcohol cravings or reach full abstinence or not, and takes account into their previous response to medications and any contraindications they may have. Shared decision making, and informed consent with the patient is very important, they need to have buy into your plan for it to work. And combining this drugs with psychosocial interventions are essential to make this plan work. The medicines are not magical cures, they must be combined with other interventions, regular review and sort of a whole circle support around their lives to make it work. So, it’s not just the healthcare service, but also probably their friends and family and partners that can really achieve, let them get off the alcohol and achieved abstinence.

Kieran Reynolds
That’s great and we will include a link to the NICE guidance again within the podcast blurb.

Now, Leslie although pharmacy professionals working in primary and community settings may not see these patients or manage these patients regularly, how can they help support these patients in the community?

Leslie Wong
Pharmacy professionals that work in community pharmacies or in primary care are in a unique position. You’re often the most accessible part of the healthcare system, and you see these patients regularly, especially in community pharmacies where they don’t need appointments. You can provide, you know, public health messaging and give advice on what the safe drinking levels are and explain how to calculate, you know, what is a unit of alcohol. You can signpost patients, or their families or loved ones to useful resources on the internet like DrinkAware or their local alcohol services or Alcoholics Anonymous, something like that, for them to get further help. And you can also introduce them to these screening tools that we talked about like the AUDIT-C or the DrinkAware’s drinking check, and if you have time you can do it with them if they’re up for it too. You can support adherence to treatment plans and lifestyle changes and talk to them about how they’re getting on with it. And you can also provide some advice on nutrition and supplements because many patients may be vitamin deficient and so you can ensure that they’re actually taking thiamine if they’re at risk of Wernicke’s encephalopathy.

And just as importantly, you know, showing empathy, giving them time and reducing stigma about alcohol use is crucial when you talk to them, making them realise that it’s normal to have this problem and you’re there for them, does, you know, is more important than you can think. And people need to feel safe about talking about their drinking without fear of judgment by everyone to really successfully stick to their plan and achieve abstinence in the long term.

Now, the UKHSA have a structured advice tool which we can share and there’s a course there that helps healthcare professionals identify individuals whose drinking might impact their health, and it provides you [with] information on how to deliver simple structured advice to patients and they also split the course so that it’s tailored to your practice setting such as in primary care, in the community pharmacy, or hospital, or dental team. So, going through this course will make you more confident and more prepared when a patient rocks up to your, when you encounter a patient and you feel like you have to give some alcohol related advice.

Kieran Reynolds
Thank you. And that course that you mentioned Leslie is the e-learning for health alcohol identification and brief advice program, and we’ll include a link to it again within the podcast blurb alongside the UKHSA alcohol structured advice tool which you mentioned.

Now finally Leslie, do you have any advice if patients who are drinking heavily want to stop drinking abruptly.

Leslie Wong
So, this is a little bit of a catch-22. If someone is physically dependent on alcohol and drinking a lot suddenly stopping drinking can be dangerous and potentially life threatening because the body has adapted to functioning with alcohol always there. So, for people who are alcohol dependent but not admitted to hospital, offer them advice to avoid a sudden reduction of alcohol intake and provide information to, how to contact local alcohol support services, and they will come up with a plan to do a managed reduction. And never abruptly stop drinking alcohol if you are alcohol dependent without medical advice or medical supervision. That’s the main message here.

Kieran Reynolds
Great, thank you, and that’s really clear.

So that’s all from us here at SPS for this episode of our liver podcast series. Thank you for tuning in and we’ll be back with another episode soon, and thank you Leslie for all your contributions to today’s podcast. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will make sure you’re always informed of our most up to date content and you will receive news of upcoming events. You can also find more about the BHPG on the BASL website or follow them on X (formally known as Twitter) @heppharm. You can also stay with in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service.

Thank you, and bye bye for now.

Kieran Reynolds
Hello, and welcome to our liver podcast series from the NHS Specialist Pharmacy Service (SPS) in collaboration with the British Hepatology Pharmacy Group (the BHPG), where we discuss issues surrounding the understanding and management of liver disease. The incidence of liver disease in the UK is increasing and it is important that healthcare professionals are all equipped to manage patients with liver disease and that they have an awareness of the risk factors.

My name is Kieran Reynolds and I’m an Advanced Specialist Pharmacist working in the Medicines Use and Safety team here at NHS SPS and this podcast series has been co- developed with Helen Boothman, Lead Hepatology Pharmacist at St George’s Hospital and past chair of the BHPG.

This is episode ten in the liver podcast series, and we would encourage you all to listen to the previous podcasts available on the SPS website. On today’s podcast, we’re delighted to be joined by Fatema Jessa, Consultant Pharmacist in Hepatology and liver transplant, and NCL Digital Pharmacy Network at the Royal Free London NHS Foundation Trust. Hello and welcome, Fatema.

Fatema Jessa
Hi, Kieran, and thanks for having me.

Kieran Reynolds
So, Fatema, we’ve heard in previous podcasts about liver disease, cirrhosis, and in this episode we’re going to be focusing around liver transplant. For listeners who haven’t come across this topic, can you give them a brief explanation as to what it is and why it’s performed.

Fatema Jessa
Yeah, of course, yeah. So, a liver transplant is a lifesaving surgery during which a diseased or a non-functioning liver is replaced with a healthy liver from a donor. So, in a majority of cases for adult liver transplant, this will be a deceased donor, but sometimes a healthy living donor can also donate a part of their liver. And as we know, the liver is the only organ that can regenerate and so the donor’s liver will grow back to the normal size after surgery, and so will be donated part of the liver.

So, liver transplantation is usually carried out when the liver is damaged to the point that it can no longer carry out its normal functions, so, this is also known as end stage or decompensated liver disease. And there can be different causes to this. So, for example damage from excessive alcohol misuse, infections such as hepatitis B, C, autoimmune conditions such as Primary Biliary Cholangitis, and other diseases such as metabolic associated steatotic liver disease, or MASLD.

And at the moment, the most common indications for liver transplant in the UK are for steatotic or ‘fatty’ liver disease which can occur as a result of alcohol or non-alcohol related conditions, and also autoimmune liver disease such as primacy sclerosing cholangitis (PSC), or primary biliary cholangitis (PBC). There are also other indications, so for example, more acute indications for liver transplant where patients are listed urgently due to acute liver failure. And this can occur due to a variety of causes such as paracetamol overdose, acute viral hepatitis infections, and other drug induced liver injuries (or DILIs).

Kieran Reynolds
And for more information about cirrhosis, MASLD, PBC, AIH, and viral hepatitis have a listen to our previous podcasts within this series.

Now Fatema, would every trust perform liver transplants, or are there specific specialist centres across the UK that will perform them?

Fatema Jessa
Yeah, that’s a good question. So, no, not every trust, but there are actually seven centres across the UK for adult liver transplants and three for paediatric transplants. And so, as you can imagine with just a few centres, there is a long waiting list for liver transplantation. Currently it’s sort of around 650/700 people, but that number can fluctuate from time to time. So now the process of being listed involves various assessments to confirm the indication for the transplant and the fitness to undergo major surgery. And the findings of these assessments are presented to the local multidisciplinary team (or MDT meeting), where an agreement is then made to list the patient or not for a liver transplant. And once they are listed, when it comes to organ allocation, this occurs on a national basis with the National Liver Offering Scheme (or NLOS), which is based on a transplant benefit score. So, this consists of twenty-one different factors related to the recipient and seven factors relating to the donor. So, you know, quite a comprehensive process, and it also integrates the patient’s expected survival without transplant compared to after a transplant. And the aim of this scoring method really is to improve that equity of access, reduce the mortality on the waiting list and to optimise outcomes.

Kieran Reynolds
And for those who would like to learn more about liver transplantation, we will include links to resources from the NHS Blood and Transport and the British Liver Trust within the podcast blurb.

Now, Fatema, how are patients who have had a liver transplant managed both in the immediate post-transplant period, but also long term?

Fatema Jessa
Yeah, so, following a liver transplant, these patients are often started on a combination of immunosuppressant drugs, mainly, including calcineurin inhibitors. So, these could be like tacrolimus or ciclosporin, as well as other immunosuppressant agents such as prednisolone, which is a steroid, mycophenolate mofetil or azathioprine. They may also have additional drugs in the immediate post-transplant period, most of these which are eventually stopped, but they will always remain on immunosuppression to reduce the risk of rejection of their new liver.

So, immediately after surgery, after that transplant they spend a few days on the ICU and then all being well, they’re stepped down to the inpatient ward. Now the duration of hospital admissions can vary depending upon the complexity of the patient, the complexity of the surgery, and also the patient specific like post-transplant recovery. But if everything runs smoothly patients can be discharged in and around ten days following their surgery, which may sound quite soon for such a big, complex surgery.

So these patients are monitored very closely in the initial few weeks following their transplant with regular outpatient visits at the transplanting centre. And after around three months, once they’re stable, they can be discharged to their local hospital to allow care to continue closer to home. With only, sort of, seven centres for adults in the UK, you can imagine patients come from far and wide to these centres. And consultants from the transplanting centre usually have close working arrangements and referral pathways in place with local centres. And we also have some outreach clinics where our consultants go to various other hospitals to run clinics from there, and this allows for really great collaboration between the centres and benefits patients to be able to have their care locally to where they live. And once stable, patients can then be reviewed every six months where they have the bloods checked to keep an eye on their liver and their renal function as well as their drug levels, such as tacrolimus levels. And this is to ensure that they remain in good health in the long term with a functioning graft, so the new liver, and safe prescribing of their post-transplant immunosuppression. And during these, sort of, follow up appointments, they’re asked about their general health post-surgery, as well as medication related issues such as adherence, any side effects they may have, and of course if they require any further supply. They’re also monitored closely for any infections such as bacterial, fungal or viral infections including cytomegalovirus (CMV), which can occur in immunosuppressed patients. And additionally, they also have a review of their blood pressure, their weights, blood sugars, and cholesterol levels, and this is to optimise their general health and to reduce post-transplant related morbidity and mortality.

Kieran Reynolds
And again, for those who want to learn more about liver transplantation, we will include links to the resources we’ve already mentioned. Now, Fatema, what is the role of the pharmacy team with these patients?

Fatema Jessa
Yeah, so the pharmacy team can do a lot for patients who’ve had a liver transplant, and it actually starts long before their transplant with medicines optimisation in patients with cirrhosis. So, patients with liver impairment will have pathophysiological changes. So, for example, in the way the blood flows through the liver due to cirrhosis, reduced protein synthesis and the presence of ascites, and these can all impact the pharmacokinetic[s] of drugs. Now in these patients, there are lots of opportunities for medicines optimisation, so, such as reducing the dose of certain sedatives or opioids, stopping PPIs [proton pump inhibitors] where there is no clear indication, optimising dosing, so for example, carvedilol dosing for portal hypertension, and carefully balancing diuretic dosing to manage ascites, and also titrating medicines, so for example, lactulose dosing to prevent hepatic encephalopathy, which is a complication of decompensated liver disease. Now, there isn’t a universal drug dosing guide that will suit every patient and so, it is really important to consider the individual patient parameters such as the severity of their liver disease, any comorbidities the patient might have, and also the individual drug pharmacokinetic and pharmacodynamic data when making dosing decisions. And as you can imagine, this makes a job of a hepatology pharmacist very interesting every day!

And post-transplant our specialist pharmacists in the ICU setting are closely involved in the post-op management whilst these patients are in the ICU and once stabilised and stepped down to the specialist ward, specialist ward based pharmacists also have considerable input. And so you see that every team of pharmacists across the settings can play a big role in managing these patients. And the role of hospital pharmacy teams involve functions such as medicines reconciliation, dose optimisation, therapeutic drug monitoring for narrow therapeutic index drugs such as tacrolimus as well as medication counselling. In addition, we go on consultant ward rounds where we advise on drug dosing whilst considering biochemical and clinical parameters also.

Kieran Reynolds
And don’t forget the SPS medicines monitoring tool which contains a number of monographs for different immunosuppressants used in liver and other solid organ transplants, and you can access that via the SPS homepage.

Fatema Jessa
And speaking of ward rounds, we also attend microbiology ward rounds where we input on antibiotic and antifungal prescribing and dosing decisions, ensuring prudent and appropriate antimicrobial and antifungal use. And we also liaise very closely with our virology colleagues to input on antiviral prescribing decisions.

And so, the role of the pharmacy team is very much based around close working with the entire multidisciplinary team [MDT]. As such, we also attend the MDT meetings, which is really important in the case of complex patients where we work with our colleagues to provide specific expert pharmaceutical management advice in situations where the evidence is limited. And so, we often have to go back to our foundational knowledge and carefully consider the pharmacokinetics and pharmacodynamics of drugs in relation to that individual patient case.

And of course, in addition to our ward based roles, pharmacy teams are also heavily involved in writing clinical guidelines, conducting audits and research, which all aim to improve patient care and provide education and training to a wide variety of colleagues, including doctors, nurses, pharmacists, as well as students and pharmacy trainees. We regularly support our clinical teams as well by conducting literature reviews and independent pharmacist evaluations for new therapies, and particularly for the more complex patients requiring specific approvals.

And finally, it’s worth mentioning that we also support service development initiatives, so such as working with NHS England or new commissioning pathways up to allow care closer to home, as well as optimising medication access pathways locally by working with our outpatient and home care pharmacy teams. So, there’s a lot more exciting and interesting work which keeps us very busy, including running outpatient clinics, conducting drug expenditure analysis, as well as being involved in regional and national committee work.

Kieran Reynolds
A very busy day for you all indeed! And what about future initiatives? Are there anything on the horizon that could affect the way that we work as pharmacy teams within this setting?

Fatema Jessa
Well, yeah. So, you know, we’ve come a very long way as a profession, haven’t we in the last 20 to 30 years and I see our roles evolving and transforming even more. So, of course, we have the exciting prospect of pharmacogenomics and individualised medicine, which may influence prescribing decisions in the future, and I’d like to think that the pharmacy profession will be heavily involved and even leaders in this area. So, for example there’s some research that the CYP3A4 genotype can modify the pharmacokinetics of tacrolimus. Now, what this means in terms of patient outcomes is as yet unclear, but as the area grows, I hope so will our knowledge and expertise in supporting the best clinical outcomes for our patients. And also, an area of personal interest, we have, of course, the developing digital health technology, the impact of AI, and of course the expansion of clinical roles for pharmacists across all sectors. So, we have some very exciting things to look forward to.

Kieran Reynolds
Great, thank you. And for those who want to learn more about optimising medicines in patients undergoing liver transplant, we will include a link to a Pharmaceutical Journal (or PJ) article about this topic within the podcast blurb.

Now, Fatema, in recent times, we’ve heard a lot about the NHS shift from hospital to community. Do you think we’ll see these patients managed in the community in the future?

Fatema Jessa
Yeah, so, we have heard about the delegation of services to the Integrated Care Board (or the ICB) and although this has affected quite a few areas, in terms of liver transplant, [as] it is classed as a highly specialised service, and so for that reason, for now, it will continue to be centrally commissioned, and so care will continue to be provided via specialist centres. However, patients with a liver transplant are at risk of developing comorbidities in the future such as cardiovascular disease, diabetes, hyperlipidaemia, obesity, and osteoporosis. And these are all conditions that can be managed in the community setting. Having said that, I think it’s important to be mindful of the complexities of post-liver transplant patients such as the potential for renal dysfunction, drug-drug interactions, and of course to tailor medication doses accordingly.

Kieran Reynolds
And how can primary care pharmacy professionals help these patients at the moment?

Fatema Jessa
Yeah, so, primary care pharmacy colleagues are actually a really important profession, in terms of their role in managing post-liver transplant patients. So, for example, patients may be prescribed a new medication, say a short course of antibiotics or, you know, a patient may pop into the local community pharmacy to purchase over the counter medications such as ibuprofen, or maybe even herbal medication, such as St John’s wort. So, it’s really important to check for drug-drug interactions with any new medicines, including herbal medicines, as these patients will often be on lifelong immunosuppression with narrow therapeutic index drugs, such as tacrolimus or ciclosporin, so even small changes in the exposure of the drug can lead to serious adverse events including toxicities, or even graft failure. So, for example, a short course of clarithromycin, say, to treat a chest infection, can greatly increase the concentration of tacrolimus, and may result in a hospital admission. So, it’s really important to look out for and prevent these potentially very dangerous drug-drug interactions (or DDIs). And useful resources to check for DDIs include: the individual product Summary of Product Characteristics (or SPC), the BNF of course, and where available Stockley’s Interactions Checker accessible via MedicinesComplete.

And similarly, we would want to avoid the use of NSAIDs, (or non-steroidal anti-inflammatory drugs), such as ibuprofen, and herbal medicines such as St John’s Wort which we know is a CYP [cytochrome] enzyme inducer. Now fortunately, these patients are counselled and supported very, very well by the entire multidisciplinary team, including our fantastic liver transplant coordinators, so the patients should also know to always check before starting any new medicines. I think what can sometimes get tricky is that these immunosuppression medications may not always be listed in the National Care Record because they’re often provided by the transplanting centre or by the local hospital, and that’s why it is vital to always ask the patient about their current medication when counselling patients in the primary care setting.

And I think primary care colleagues also have a really important role in checking for adherence to immunosuppressants. So, simply asking patients how they’re managing with their medications can make a really big difference. So, if they raise any issues or mention that they’ve stopped taking their medicines, it’s vitally important to signpost them back to the specialist transplant team for further support.

And primary care colleagues may also get queries about travel vaccines or seasonal vaccines such as the ‘flu vaccine or the covid vaccine. Again, it’s really important to check that the vaccination and any travel prophylaxis medication is safe to take in the context of liver transplant. And live vaccines should ideally be avoided in these immunosuppressed patients.

And patients sometimes may also find it difficult to access their medication or sometimes pay for their post-transplant medication. Now recognising the importance of not missing any doses, it is important to signpost the patient appropriately, for example, by encouraging them to contact liver transplant coordinators, say, if they need a supply, an emergency supply of their medication. So, transplant centres usually have an on-call service available 24 hours a day, seven days a week, so they can always get in touch with their specialists in the case of an emergency. And in terms of payment for their medication, patients may find it helpful to know what can help with their prescription charges, so, for example, information about the prepayment certificate or relevant exemptions for them, if applicable.

And finally, it’s worth mentioning that post-liver transplant patients may also have, or indeed develop other comorbidities, so it’s really important to counsel patients about the safe use of all medication they might be on, as well as providing healthy living advice such as weight management, blood pressure control, blood glucose control, and so forth. So, primary care colleagues may, you know, only see one or two post-liver transplant patients a year, but they have a vital role in keeping these patients safe and preventing avoidable medicines related harm.

Kieran Reynolds
That’s great, thank you. And for further information on vaccines, we’ll include links to the Green Book and the NHS Blood and Transplant’s information on liver transport medicines. And we’ll also include a link to the NHS BSA information on the Prescription Prepayment Certificates.

That’s all from us here at SPS for this episode of our liver podcast series, and indeed this is the last episode in this series and thank you to all of you who have tuned in. Thank you very much to Fatema for all your contribution to today’s podcast and to all our expert speakers throughout the series. We’re always keen to hear from you about suggestions you have for resources or events you want us to cover, and our contact details are available on our website. Please remember to register on our website and to opt in to receive our weekly SPS bulletin. This will ensure that you’re always informed of our most up to date content and you will receive news of upcoming events. You can also find more about the BHPG on the BASL website or follow them on X @heppharm. You can also stay in touch with SPS by following us on LinkedIn, simply search NHS Specialist Pharmacy Service. Thank you and bye bye for now.