Liver Health in General Practice
Serena
Good evening, everyone, and welcome to tonight's webinar Liver Health in General Practice. We are joined tonight by presenters are Professor Simone Strasser and Dr Natasha Feingold. My name is Serena and I will be your RACGP representative for this evening. Before we get started, I would like to make an acknowledgement of country. We recognise the traditional custodians of the land and sea on which we live and work, and we pay our respects to elders past, present and emerging. I would also like to acknowledge any Aboriginal or Torres Strait Islander colleagues that have joined us online this evening. Just a few housekeeping notes. If you cannot see a panel like this image on the slide, hover your cursor over the bottom section of the shared presentation screen and the panel will appear. This control panel provides you with your audio option and most importantly, your Q&A box. We have put everyone on mute to ensure learning will not be disrupted by background noise. Please chat to us. Send us your questions using the Q&A box. We will try to address questions as they come in, but in the interest of time, this is not always possible. If you have any unanswered questions, please feel free to email them through to us. I will share the email address a little later. I would like to formally introduce you to our presenters for this evening. Simone is the head of Department of Senior Staff specialists in the AW Morrow Gastroenterology and Liver Centre and medical director of the Australian National Liver Transplantation Unit at the Royal Prince Alfred Hospital and the University of Sydney. She is Past President of the Gastroenterological Society of Australia and a Board Director of the Liver Foundation and Australian Community Organisation to support people with liver disease. Natasha, a GP from Sydney, who has moved to Gold Coast and works for Specialised Women's Health Clinic where she has speciality interests in chronic disease management. She is committed to quality medical education of junior doctors, and worked for many years as a lecturer at the University of Notre Dame School of Medicine. I will now pass it to Natasha for the learning objectives.
Dr Natasha Feingold
Thank you so much, Serena. We have a great evening tonight with some really high yield topics, and we have my esteemed colleague Professor Strasser, who will be here to go through some really important learning objectives today, and these are to number one, understand the common causes of liver related morbidity and mortality, identify patients at risk of liver disease, describe the GP role in the management of liver disease, including viral hepatitis, MAFLD and cancer screening. We will also identify opportunities to promote liver health, including supporting healthy lifestyle modifications. Let us get right into it and I will pass the microphone over to Professor Strasser. Thank you so much.
Professor Simone Strasser
Thank you for that. Now let me just share my screen and welcome everybody. We have got a lot to get through this evening and we are going to kick off really without any storm. We are really concerned about the rising rates of chronic liver disease and particularly cirrhosis and liver cancer, and appreciating that some of the liver cancer that we see actually arises in the setting of patients without cirrhosis as well, particularly in hepatitis B. Chronic liver disease contributes significantly to the burden of liver disease. The incidence and mortality are both increasing over time. We have got three main types of primary liver cancer that we are worried about, but we are particularly focused on hepatocellular carcinoma which, which represents over 90% of patients with primary liver cancer. The biggest risk factor still for patients with liver cancer is viral hepatitis, but increasingly we are recognising the role of comorbidities in patients with a history of hepatitis who have been treated, and that is going to become even more of a problem in the future as more and more patients with viral hepatitis are treated, but still, hepatitis B is a major driver of liver cancer in Australia. If we look at the common causes we have already mentioned some of these. Hepatitis C remains a cause of chronic liver disease, and as we will see, we have still got work to do to uncover all the people living with hepatitis C who remain at risk. Hepatitis B remains very important, related mainly to migration and in Indigenous Australians. Increasingly, metabolic associated fatty liver disease is either a cause of liver disease or a major contributor to liver disease and people with other liver diseases and always alcohol related liver disease is a major issue and again, a major contributor to liver disease, and there are other less common causes of liver disease which you may pick up if you do a liver screen and you will see some patients with these, but compared to the top four they are really quite uncommon. Any cause of liver disease can progress through fibrosis to cirrhosis, and ultimately once there is cirrhosis or it is in some situations advanced fibrosis present, then liver cancer can be the risk, and that is why we recommend surveillance for patients at risk. We are going to go through each of those top four of liver disease, and I we are going to assume some knowledge around some of these areas. I am going to run through them fairly quickly. The main message with hepatitis C is if you find it, cure it. The treatments that we have are now highly effective, and this is really a curable illness and it does not recur unless patients get reinfected. Estimated still, there are 50 million people living with hepatitis C around the world, and still to over 240,000 people die of hepatitis C per year, mainly from the downstream consequences from having cirrhosis and liver failure or developing cancer or both. In Australia, the current estimates are that we still have 74,000 people living with hepatitis C, which is certainly down from the original estimates of about 220,000 people before we had access to direct acting antivirals, but still 74,000 people living with hepatitis C who either know they have got it and have not ever had treatment for various reasons or they do not even know they have got it, and the predominant mode of transmission, as I am sure you all know, is by blood to blood contact and particularly through injecting drug use. There are tools that have been available for some time, and I am hoping that you are all aware of those and particularly the ASHM guidance which is available through their website, which is very, very helpful, and also the Australian recommendations for the management of hepatitis C virus infection that was last updated in 2022, and we are probably not going to update it again because nothing new has happened. The treatments are what they were then and are unlikely to change in the future, so I do not expect that we will have another update of that, but there is very useful guides. If you are not treating currently hepatitis C infected people, you really should be and there is very good guidance in there about how to do that, and it is very straightforward. In terms of testing, really we should be making sure we are diagnosing those people living with hepatitis C who do not know they have got it, so that is people who ever have injected drugs, people who have been in jail and people from Aboriginal and Torres Strait Islander backgrounds. People from countries with high prevalence of hepatitis C traditionally should also be tested, and for us, it is people from Eastern Europe, from some Mediterranean and North African countries, from Asian countries in particular. Also, anyone that you find abnormal liver tests or evidence of liver disease should be tested for hepatitis C and as we will see hepatitis B as well, and the most diagnoses that we see are screening at risk populations, particularly people who have injected drugs in the past or are currently injecting. When you order a hepatitis C test, it is no longer good enough just to get a hep C antibody test. You need to get an RNA test as well if it is positive, so you put in a request for reflex testing, so hepatitis C serology and if positive, please do an HCV RNA, and then you will get all the information you need. Once you know someone has got hepatitis C and you have treated them with antiviral therapy, there is no point ever doing another antibody test because it will remain positive. You just need to monitor for hepatitis C RNA if they are at risk of reinfection. In terms of management still, as we have been teaching for a number of years, you need to do that pre-treatment assessment in particularly important to identify which patients have cirrhosis. Now as the age of untreated patients is reducing and is now in the younger active injecting community, they are more likely to have cirrhosis, but it still remains important to do that, and we use an APRI test to do that, which I will show you later. Anyone diagnosed with hepatitis C, you do not need a genotype. You do not need a viral load. You just need to get on and give them a medication, and there are two available for treatment naive patients and they are very, very straightforward to use, and you need to make sure they have got ongoing support for liver health, including cancer screening if you identify them as having cirrhosis, prevent reinfection and particularly manage co-morbidities because as we are seeing what is driving particularly progression to cirrhosis and liver cancer in patients with a history of hepatitis C is their co-morbidities. It is obesity, diabetes and alcohol use. Hepatitis C is curable with our direct acting antiviral therapies. We need to offer all people living with hepatitis C treatment. Do not wait for spontaneous clearance, so if it is acute infection, just treat it as well, and we have got pan-genotypic therapies with very high cure rates, and they are available on the PBS for anyone to prescribe. Moving on to hepatitis B, it is vaccine preventable, and therefore anybody at risk really should be vaccinated, and hopefully we will have a cohort effect as we have newborn vaccination. Now we had catch up vaccination for teenagers. The transmission is around the world. It is largely perinatal transmission, but it can obviously also be transmitted through parenteral percutaneous routes or sexual transmission. Most people that we see who have been living with chronic hepatitis B, though, acquired it at birth or early childhood and come from a country of high prevalence, and in terms of numbers in New South Wales, that is largely people from China and Vietnam and all people from those backgrounds should be tested as well as anybody coming from any Asian country and African countries or Pacific island countries. There is many countries where people are at risk, but numerically the burden is particularly in people born in China and Vietnam, in our population. There is also to be aware of a lot of stigma and discrimination and always testing and a diagnosis and conveying those results need to be done in obviously a sensitive manner because there is a lot of stigma within families and within communities around a hepatitis B diagnosis because it has been associated with cancer and a whole lot of other issues that lead to stigma. It is a really ongoing big issue surprisingly. Again, the ASHM guidance documents are very, very helpful for helping you manage hepatitis B, and again, there is an Australian consensus recommendation, which was a multi-stakeholder consensus that was released in 2021. There will be an update coming in the next year or so, and there was a summary document in the Medical Journal of Australia which hopefully you have you have seen, but again a good guidance for how to evaluate patients and treat. In terms of testing, again test the priority populations, and in this setting, it is mainly people from those intermediate or high prevalence countries and people from Aboriginal and Torres Strait Islander background, and again anyone with evidence of liver disease must have a hepatitis B test done, and when we do hepatitis B testing, we need to really figure out whether a patient has got chronic hepatitis B, so that is a that is the surface antigen test or they have been exposed to hepatitis B in the past, which is a core antibody test, and that is important when we are going to immunosuppress some people because they might need antiviral treatment in that setting, and also we want to know if people have been vaccinated before, so the Anti-HBs test will tell us that. If all of those are negative, that means that person is susceptible for hepatitis B and should be vaccinated. If there is surface antigen positive and you have done it in the context of screening, then that person has got chronic hepatitis B. It is unlikely to be acute hepatitis B in that setting, and then we need to go on and identify the phase of infection and gets a bit more complex. I am not going to go through a lot of detail around that because that is another hour webinar. In terms of management and treatment, we do need to assess the phase of infection. All you need to do there is liver test E antigen, E antibody and HPV DNA, and again a fibrosis assessment in all patients at baseline. All patients should be considered for treatment, but for about 80% of patients that do not actually fulfil criteria for treatment on current guidelines, although that may expand in the future, and if you are not approved for bass 100 prescriber for hepatitis B, then refer to either a GP who is an S-100 community prescriber or to a liver specialist or ID specialist who specialises in hepatitis B if they have an indication for treatment according to guidelines. We are not going to see them in specialist clinics in somebody who has got hepatitis B, they have got completely normal liver tests, normal platelet count and a low level of HBV DNA. They do not meet statewide referral criteria and they will not be seen in specialist services, and you should be able to continue to monitor them with annual testing in in your own practice. If there is any concern for cirrhosis, obviously they should be referred, and again with any viral hepatitis, lifestyle management is important because particularly obesity, diabetes and alcohol again drive progression of disease and hepatitis B, and I think that we have missed that messaging and we are now seeing more and more people living with hepatitis B. They might be on long term antivirals, but they are living with obesity and drinking too much and they are at risk of progression of liver disease and cancer in particular, and again managing their social and emotional wellbeing, recognising stigma in both hepatitis C and hepatitis B patients.
Now moving on to the big one. This is the one that is that is rising rapidly, and we are terming it at the moment metabolic dysfunction associated fatty liver disease or MAFLD. This affects to 35% in some populations, even 40% of adults around the world, and increasingly we are seeing in adolescents and young adults as well related to the obesity epidemic. About one in 5 to 10 people will develop significant liver fibrosis, progressing to cirrhosis and at risk of liver cancer. That is not inconsequential when you realise there is probably 6 million people, adults in Australia living with MAFLD. There is also an increased risk for their extrahepatic complications, and by that I mean, metabolic complications, cardiovascular disease, cerebrovascular disease and malignancy including liver malignancy but also non liver malignancies, any cancers can be related to obesity. It is also as I mentioned a co-factor in disease progression for other liver diseases. It is often we do not see it in isolation. We see that there are other co-factors driving it, and therefore we have to look for those co-factors. MAFLD can be reversed in its early stages even when there is fibrosis evolving, if you get weight down and increase physical activity then it can reverse. We have changed the nomenclature, as you are probably aware of from non-alcoholic fatty liver disease to in Australia, we are now using metabolic associated fatty liver disease, which really highlights the role of metabolic dysfunction and also allows for a diagnosis in people with other causes of liver disease because it is a standalone diagnosis that needs its own attention. You might have also seen the literature regarding the MASLD terminology, Metabolic Associated Stereotactic Liver Disease, which has been adopted particularly in Europe and North America, but in Australia and in most of Asia Pacific, we are using the MAFLD definition, which I think suits our purposes very, very well. The reason for that is because we can make a positive diagnosis of MAFLD based on finding a patient with fatty liver disease. If we do an ultrasound and the report comes back, there is evidence of fatty infiltration or they have got mildly abnormal liver tests or they may get to a liver biopsy showing fatty liver and they have got particularly obesity or they have got type two diabetes and that is a positive diagnosis of MAFLD. We do not need a biopsy in that setting to prove it. We do not need any other testing. They have got fat in their liver. They have got risk factors, particularly obesity or diabetes. They have got me MAFLD. If they are of normal weight, they can still have MAFLD, but you need to have at least two other metabolic risk abnormalities such as hypertension, dyslipidaemia, pre-diabetes, etc. We can now make a positive diagnosis rather than it being a diagnosis of exclusion, which it really was in the past, and that allows us to make the diagnosis in the setting of people with other liver diseases from alcohol or viral hepatitis in particular. When we find somebody with MAFLD, importantly, we always need to assess for fibrosis and it can be done really easily, and I will show you the calculator, but we do a FIB-4 assessment which is just based on age AST, ALT and platelet count, very simple. If we are above the threshold of 1.3 then they need a secondary test to assess their fibrosis, and in our context at the moment that will be with a FibroScan or transient elastography. Again, the key to management of MAFLD is weight loss, and that can be done through healthy eating, through dietary modification, through increasing physical activity, or increasingly through pharmacotherapy or bariatric surgery as I will mention again and again, managing comorbidities is essential because these patients die largely of cardiovascular disease and cancer before they die of liver disease unless they have got advanced fibrosis. We need to treat their type two diabetes and treat to target and get that under control. We need to assess and modify their cardiovascular risk factors because they are going to die of cardiovascular death before liver disease.
Dr Natasha Feingold
Professor Strasser, can I just interrupt? We had a question from the audience. How often do you need to do the FibroScan in MAFLD?
Professor Simone Strasser
You only need to do the FibroScan if that FIB-4 is over 1.3. If it is less than 1.3, they do not even need a FibroScan because it has got such a high negative predictive value for detecting fibrosis. A very low FIB-4 score, that means their AST and ALT numbers are pretty low and their platelet counts are normal, and you just put it into the calculator. Then if it is less than 1.3, they do not need a FibroScan at all. If you have done a FibroScan in the context of a FIB-4 over 1.3, but the FibroScan is less than eight, we just recommend checking their FIB-4 again in 2 to 3 years and if it is still high doing another FibroScan then. If they are greater than 8, they will be seen in liver clinic and we will get to that in a minute okay.
In terms of healthy lifestyle management, again you should you know all this. You do this every single day, recommending a healthy diet, in fact, there is good data for a mediterranean diet, which is seafood and plant-based foods and cereals, as you know. It has got positive benefit in MAFLD as it does in other metabolic disease. If they need to lose weight, obviously we need to get a caloric deficit. Avoiding alcohol and sugar sweetened drinks and probably also the sugar free drinks with the sweeteners. There is increasing evidence that actually they are not that great for metabolic disease and water is a much better option. Smoking cessation is important. It drives liver disease as well as lung disease and cancer and all the other problems, but it also drives liver disease. Now, the only good thing you can do with your diet, apart from all of those things is coffee, and there is emerging evidence that drinking coffee and maybe three cups of coffee a day as a minimum may be beneficial for metabolic associated fatty liver disease. That is a good news story, and the patients love hearing about that. Physical activity is obviously important, and for some people, they are not going to be able to do five hours a week of moderate intensity physical activity if they have never done it. They need to build up to it, but just getting them moving rather than not moving is the first step of that, and again, you do this every day, but you have got to keep reinforcing it. There are referral options to the Get Healthy service in New South Wales, which has got a lot of this advice and offers evidence based free phone and online coaching, which is an enormous benefit and particularly being free, and as I mentioned earlier, if they are having trouble with their weight, we have now approved medications for weight loss, although none of them are on the PBS at this point and hopefully they will be in the future, including for patients living with MAFLD, and bariatric surgery is effective for MALFD as well.
Dr Natasha Feingold
Professor Strasser, with those medications, are there any studies to show that they improve MAFLD?
Professor Simone Strasser
People may be aware that there is a recent publication, the New England Journal of Medicine, using the higher dose of semaglutide, the 2.4 mg a week compared to placebo was a positive study in patients with moderate to marked fibrosis. It was not a cirrhosis study. It was patients with that higher FibroScan but without cirrhosis. They were all biopsy proven and they met the primary endpoint in that study. It was a positive study, and we are optimistic that we may get an approval specifically for MAFLD using, that is Wegovy, a higher dose of semaglutide. Studies with Mounjaro are not available yet. The only data we have got at the moment is with that. There are other medications with positive phase three trials, but they are not yet available in Australia and I am not sure they are going to be, but we are most likely to see Semaglutide approved certainly with positive benefits in this area and I would not be scared of using it. It drops their weight. It also improves their liver histology and their liver numbers. Thank you for that question.
Moving along, the other really important liver disease that I think is underplayed in comparison to the other three is the impact of alcohol and alcohol related liver disease, and we are no longer called this like many person centric changes in terminology. This is alcohol related or alcohol associated liver disease rather than alcoholic liver disease now, and that has been accepted terminology. Alcohol related liver disease is important, and alcohol consumption is responsible for about 4.5% of the burden of all disease in Australia, but it is a major contributor to liver disease. It accounts for about 25% of decompensated liver cirrhosis. Again, it is a driver in patients even if they have got a diagnosis of prior hepatitis C that might have been treated and even hepatitis B, so 1 in 3 people aged 14 and over consume alcohol at risky levels, as I am sure you are aware, and we have got Australian alcohol guidelines for healthy adults that say that if you stick to under ten standard drinks per week or less than four standard drinks on any one day, that you are probably not at a harmful level of alcohol, although that does not apply to people who have significant fibrosis or cirrhosis who should be abstinent of alcohol, and we have the alcohol guidelines that are available. It is important to identify which of your patients have a significant issue with alcohol, and increasingly I realise how bad I am at doing this, and I do this all the time. An audit C questionnaire is a good place to start, although patients will underplay the amount of alcohol they are drinking. It is not gin, it is just water. The mini questionnaire is just three questions. How often do you have a drink containing alcohol? How many standard drinks containing alcohol do you have on a typical day? And how often do you have six or more drinks on one occasion? And that is quite a good screen for identifying people with alcohol, although they will underplay, and we are learning that now. We have got indirect biological markers. Their pattern of liver tests, particularly if the GTT is high, if the AST is higher than the ALT or if the MCV is high, but we now have the PEth test and we can access this in our service. It is available through the RPA laboratory through New South Wales Health Pathology, and this is like the HBA1c of alcohol. It is an amazing test. It looks at this specific direct alcohol biomarker and it can indicate levels of alcohol consumption quite accurately over the past month. In patients, who deny alcohol where you are really pretty much sure it is due to alcohol or they say they are just drinking a small amount of alcohol and you suspect it is a lot more. This is actually an incredibly useful test, and it has been applied in populations where we think the cause of liver disease is their metabolic associated fatty liver disease, and they deny significant alcohol. We can find high PEth levels in those patients as well that they are underplaying the amount of alcohol and how that is driving because of course this is then another target for therapy if we can identify that and support our patients to reduce or hopefully abstain from alcohol if they have got significant liver disease. This is a new test. It is not yet funded on the MBS, but we are performing it through RPA laboratories and through our liver clinic. We will order it where we think it is applicable. In terms of management and treatment, obviously encouraging adherence for everybody to the Australian alcohol guidelines and in those with advanced liver disease, complete abstinence. There is brief advice or intervention that you can do the first when you have any consultation. Using the FLAGS approach and we have pharmacotherapy available on the PBS and particularly naltrexone and acamprosate have a major role in these patients. It is essential that patients with alcohol related cirrhosis completely abstain from alcohol, and I have already made that point several times and that is that several lines of data here that patients with cirrhosis who receive medical addiction therapy have a significantly lower incidence of hepatic decompensation. Patients with compensated cirrhosis who abstain from alcohol for reduced risk of cancer, and patients with decompensated cirrhosis who abstain from alcohol have an improved survival. Across all stages of more advanced liver disease, they benefit from complete abstinence and a reduction in alcohol consumption does not achieve those end points. We have various ways that we can assist our patients in coming off alcohol through our drug and alcohol specialist advisory services and alcohol and drug information services, and you will have those links in the extra material that you receive if you are not already accessing those, and so really having that conversation with the patient identifying when they are ready to quit drinking in particular and making sure that they have the services available to them when they are ready.
The next area that we are going to look at is particularly a little bit more about assessing liver fibrosis and cirrhosis, and this is critical across hepatitis C, hepatitis B, MAFLD and alcohol, and therefore we really need to figure out which of those patients have more advanced fibrosis or cirrhosis. In hepatitis C, before you start treatment and also in hepatitis B, even if a patient is not on treatment, doing this serially always in MAFLD at baseline, but also if you do not think they have got much fibrosis then every 2 to 3 years and in patients with persistently abnormal liver tests, although being aware that these fibrosis markers in patients who have got active hepatitis such as autoimmune hepatitis, they will be very high and will not necessarily reflect the amount of fibrosis, and of course, anybody who has got clinical features of cirrhosis, you will probably be able to pick up because they are enriched anyway, and the tests that we use are the APRI score, which is just the AST to platelet ratio index, the FIB-4 score which we have already mentioned, and the FibroScan or transient elastography. There are calculators available. This is the APRI calculator. It is available on various apps where you just plug in the AST and the upper limit of normal of ASD and the platelet count and it will give you that APRI score and less than 1 is regarded as not of concern. Greater than 2 is very likely to be cirrhosis and greater than 1, we are pretty worried that there is fibrosis building up. That is where we put the threshold. The FIB-4 score is the one recommended particularly for assessing patients with metabolic associated fatty liver disease. It is just based on the age, the AST, the ALT and the platelet count, and you put those numbers in on the Liver Foundation website. Not only will you find a whole lot of information around all causes of liver disease and support for your patients, but you will also find a FIB-4 calculator where you can plug those numbers in, and they will then link to the Australian Recommendations for management and assessment of patients with metabolic associated fatty liver disease. I urge you to to use the calculator as a routine in your patients with MAFLD. Elastography or FibroScan is a noninvasive test that measures liver stiffness. It is available through liver clinics and sometimes in community settings as well. It is not the same as the fibrosis assessment that is available on ultrasound machines, which is shear wave elastography. The numbers with shear wave elastography have not been as well validated in the assessment of MAFLD, so where possible, we try and get a FibroScan, although it is not always possible depending on where the patient is. The threshold that has been set in MAFLD particularly is 8 kilopascals and that suggests that the patient has got at least moderate fibrosis. Under 8, we are less worried about the amount of fibrosis and greater than 12.5 or sometimes 15, depending on what the liver disease is, is consistent with the presence of cirrhosis, and over 20 is associated with more risk of portal hypertension and increasing risk of liver cancer. We have an assessment algorithm for patients with MAFLD. That is part of the GESA consensus guidelines which are currently available on the GESA website as well as through health pathways and will be published in the MJA, hopefully, before the end of the year, but we will see. What this says is, if you have got patient with MAFLD, always assess for the risk of advanced fibrosis using a FIB-4 less than 1.3, continue to offer lifestyle advice, recognising that their risk is related to their cardiovascular risk and their malignancy risk. You really need to be still managing their lifestyle, their weight, their alcohol consumption and everything else. Once the FIB-4 is over 2.7, then that person is much more likely to already have cirrhosis and they should just be referred straight to a liver specialist. Between 1.3 and 2.7 then they do need that second test which is usually a FibroScan. In the future, we may have direct serum tests such as an ELF score or a Hepascore, which is just you send off a blood test and it comes back with a number that tells you how much fibrosis that patient is likely to have. We are hoping that that sort of testing might be on Medicare at some point in the future. Again, if you get a low score on that second test, then you just go back to repeating their FIB-4 every three years or so. If they have got a high value on that, then again they should be referred to us for further assessment.
Dr Natasha Feingold
Professor Strasser, if there is one test or one assessment to do, whether it is APRI, FIB-4 or the FibroScan if? If there is only one, which one would be the one to do?
Professor Simone Strasser
Well, you have always got access to a FIB-4 because that is just your AST, ALT and platelet count. Every time you do a blood test, you have got access to a FIB-4. I would say FIB-4. You do not always have access to a FibroScan and we do not have the resources to do FibroScan on 6 or 7 million people who are living with fatty liver disease. Really it has to be a serum based test which is at the moment a FIB-4 test and it has got its issues, but at the very low levels, it excludes people with significant fibrosis. That is the test you should be doing. Of course, if they see me in clinic having been referred, I will always do a FibroScan, but it is because I have got one in my room. It depends on where you are.
Dr Natasha Feingold
Someone asked is it possible for GPs to learn how to perform the FibroScan because it is difficult to access in rural areas?
Professor Simone Strasser
If you have got a spare $150,000 to buy one, sure. Anyone can learn how to do a FibroScan. There is a bit of a learning curve, but you can be signed off. The machines are expensive, and at the moment, they are largely sitting in liver services. They are expensive. They come from France and they vary according to the Aussie dollar, but that is a problem. The shear wave elastography is probably the next best if you are doing the secondary test, but the first test should still be a FIB-4 because you can exclude a whole lot of people who do not need that next test.
Dr Natasha Feingold
Yeah. Thank you.
Professor Simone Strasser
Again, in all of them and I keep reiterating this, they need to be managed for their obesity. They need to have their type 2 diabetes optimised, their cardiovascular disease assessed for and managed and their other comorbid conditions such as obstructive sleep apnoea, their CKD and everything else that goes along with the cardiometabolic syndrome. Really, really important. These patients are at risk and their MAFLD may pre-date their other consequences of metabolic dysfunction by up to 10 years. It may pre-date their emergence of diabetes. If you can identify their MAFLD and get their weight down and get them moving, you may prevent their future diabetes. It is a really important trigger to prevent illness down the track. Referral to a specialist is obviously a question. We cannot see every patient who has got metabolic associated fatty liver disease in New South Wales. We have now got statewide referral criteria which I am hoping you are all aware of because we will not see patients in our clinics just because they have an ultrasound showing steatosis if they have got normal liver tests and a FIB-4 score, that is less than 1.3. We do not have capacity. In fact, in our service, even if they have got mildly abnormal liver tests and they have clearly got MAFLD and no other diagnosis and their FIB-4 is less than 1.3, we do not have capacity to see them either. They are the ones that you need to retain in primary care, focus on their metabolic health. Obviously, if they have got cirrhosis, they should be referred. Now liver cancer surveillance is important. Liver cancer and HCC is the most rapidly rising cause of cancer death in Australia. We see so much now compared to what we used to see. The recommended surveillance at the moment is six-monthly ultrasound and AFP recommended for all people with hepatitis B, men over 40 and women over 50 from Asian backgrounds and pretty much everyone else over the age of 50 and cirrhosis of any cause is always recommended for ultrasound and AFP and we have got clinical practice guidelines from the Cancer Council around that. We might move on to the the case, Natasha. You are going to run through this.
Dr Natasha Feingold
All right. Thank you. Well, we have a very common case that we see in general practice. We have somebody come through our door who is a 52-year-old male who is migrated from China with his family. He lives with his wife and his two teenage kids. He has got parents and a brother that also live in Sydney, and he is in the obesity category with a BMI of 27 and I think, Professor Strasser, are you going to talk to that?
Professor Simone Strasser
Yeah, sure because you might go, oh, but that is not obesity. I thought 30 was obesity, but this guy is Asian and therefore the cutoffs for BMI for obesity are much lower and 27 is in the obesity range, class 1 obesity. That is why we make that point. You need to know the ethnic background of your patient to apply BMI and to assess for obesity, but this this guy meets obesity.
Dr Natasha Feingold
Yeah that is super important. He also has impaired glucose tolerance. He is drinking two whiskys per day which puts him at a moderately high alcohol consumption. He is a non-smoker and he has had an ALT of 72. I know I am rushing through this, but I want to make sure that we get through everything. These investigations that we would initially order are the usual, the full blood count, the hepatitis B serology and if you have forgotten all the acronyms and you cannot remember your medical school knowledge, you can always write ?chronic hep B on the pathology form to to get that ordered. Then the hepatitis C reflex serology and then HbA1c, fasting glucose, lipids, and then we would send them for a liver ultrasound. I think there was a question in the chat box about ordering reflex hep C serology that apparently in New South Wales it can be hard for them to automatically order it that they charge a private fee and there can be some issues with that. Hopefully, you can still get that done. Maybe we will move on to the actual results. In looking at these, I might just ask Professor Strasser what is your initial reaction when you see these results?
Professor Simone Strasser
I am a liver specialist, I look at the liver function tests and I look at the pattern of liver function tests as well. They are not very alarmingly high numbers. Keeping in mind, in women, we recognise that a healthy normal ALT is 19 or lower and in men it is under 30. An ALT of 72 in a man is more than twice the upper limit of normal, even if the normal in that laboratory happens to be 45 or 50, which it sometimes is in some of our laboratories around. I do not know if people heard me on the health report a few weeks ago talking about this issue as well, but an ALT of 72 is significantly elevated. Importantly, the AST is lower than that. When we see AST higher than ALT, it is a major flag that alcohol is driving the liver disease or there is already cirrhosis present, but I am not worried about that at the moment. GGT is important. Again, people underplay alcohol, and if you see particularly high GGT, that may be a pointer that alcohol is driving their disease or they have got something else going on. The other things I am looking at, I always look at the platelet count, and this guy has got a platelet count of 160. Now that is right near the lower limit of normal which is 150 to 450. That is a flag. It will not get an asterisk or a bold or whatever, but 160 is concerning because it is towards the lower limit. If you go back and look at his liver tests, his platelet count profile over a period of time, you will probably see it has been progressively falling. That is a flag that there is progressive fibrosis. We see that he is hepatitis C antibody positive but his RNA is not detected, so he does not have hepatitis C. He has probably been exposed before though and spontaneously cleared it, if he has got no treatment history, and he happens to have hepatitis B surface antigen positive and core antibody positive. He has chronic hepatitis B and then we need to get on it and assess is he e-Antigen positive or negative. What is his level of HPV DNA. He has an ultrasound which shows not surprisingly the fact that he has got diabetes and he has got steatosis that he has got high BMI and obesity, that he has got hepatic steatosis and that would not be a surprising finding. We see his HbA1c is probably acceptable at 6%, his fasting glucose at 6.2 which is a little high. He has got dyslipidaemia. He has got multiple liver diseases, this guy, he has got chronic hepatitis B and we do not know which stage. He has got metabolic associated fatty liver disease because he has got steatosis and he has got obesity and he has got the alcohol history as well, which is above the harmful cutoff for drinking as well. Lots of things for us to be managing in this guy independently, but all at the same time.
Dr Natasha Feingold
Yeah. We have probably got 15 minutes to do it. This is exactly what you were talking about, Professor Strasser. I can let you take it away from here too.
Professor Simone Strasser
Okay, so again, he has got MAFLD just by virtue of having steatosis and being in the obesity range. In summary, I am not going to go through because we do not have the time, but we can draw it out in the questions if people want is we need to target all of his liver disease drivers, his chronic hepatitis B and increasingly guidelines will probably change and the WHO guidelines are if you have got comorbidities such as fatty liver disease and hepatitis B that they are recommending now, treat the hepatitis B regardless of the level of HPV DNA as long as it is there. If they are viremic, treat it. That is not yet that situation in Australia where we have still got PBS guided cut offs for HPV DNA levels that give treatment except in the setting of cirrhosis where any level of hepatitis B DNA permits antiviral treatment. His hepatitis B may may need treatment or need monitoring. His fatty liver disease certainly needs intervention. He needs to get eating less white rice, probably less ice cream and snacks and chips and whatever else he is eating. Get his weight down into the healthy weight range and counsel him about alcohol to get his alcohol consumption down or stopped altogether. He obviously needs fibrosis assessment, and as we mentioned, his hepatitis B staging. This patient is now offered regular testing. He meets criteria for HCC surveillance because he is over the age of 40. Even if he does not have cirrhosis, it is just based on age in our current guidelines. He gets an ultrasound and AFP every six months and he has hepatitis B monitored whether or not he is on treatment or not and HPV DNA is available annually on Medicare for patients not on treatment and four times a year if they are. He needs to be regularly reassessed to see whether he meets the criteria for hepatitis B treatment, even if he does not right now and he may may develop one over time. Then offering perhaps a six monthly liver health check to bring him in because there is some of these issues are lifestyle issues such as his diet habits, his exercise habits, his alcohol consumption. You need to continually see him to remind him to stick with the plan basically. He needs to be having that HCC surveillance anyway. Now we will often do an HCC surveillance once we start seeing patients in our liver clinics, but there is no reason you cannot be doing HCC surveillance where it is indicated as well, making sure that the patients are actually getting that ultrasound and AFP level done. Then consider what tools you have got available to support regular testing and getting him back in and making sure he does not drop out of care. You may have recall reminder systems that are really, really important to make sure that patients with hepatitis B particularly remain in regular care. The key takeaways. Liver disease can often be managed in general practice. They cannot all be referred to tertiary and to specialist care. GPs play a critical role in preventing advanced liver disease and liver cancer. With hepatitis B, hepatitis C, MAFLD and alcohol, if you actually intervene, you can prevent that patient progressing to advanced fibrosis, cirrhosis and liver cancer. It is critically important. Again, remembering that their cardiovascular risk is also an important target. There are many useful tools as we have seen, and there are resources which we will share. They can guide management and assessment of patients with liver disease. Think about the liver, screen for the common cause of liver disease where appropriate, and every patient has a potential risk factor. Thank you. Then we have a few resources as well, Natasha.
Dr Natasha Feingold
I can go through and then we will send the slides out to you because there are actually quite a few resources and I think some extra slides too. Just regarding some of the the testing that we just did not have time to go through. There are a couple audits.
Professor Simone Strasser
The Liver Foundation website, it is still got available MAFLD audit. You can use that for your CME by registering your patients in this audit where you assess if they have got risk factors for MAFLD and what their FIB-4 score is and what your ongoing management plan is. Then there is also education through the Liver Foundation website that has been developed. You will see me a lot on all this in conjunction with ThinkGP. That is available through the Liver Foundation website. There is also this program that I was involved in as well through Sydney University which is some of you might have already signed up for this, that really again about implementing those MAFLD consensus recommendations and get you thinking about diagnosing, assessing and managing MAFLD in primary care. Several opportunities really for ongoing education, all of which is CME approved and a few other things in terms of what you can do.
Dr Natasha Feingold
There are other opportunities for CPD points that you can get based on the different categories.
Serena
Sorry about that. If we can stop share slides and we will go into Q&A session. Thank you so much.
Dr Natasha Feingold
Thank you so much, Professor Strasser. That was such high yield information. These are patients we see every day. It is really helpful to pick your brain and and get you to answer some of these burning questions that we have about liver disease. We actually have quite a few questions. This is probably the most questions I have seen on a webinar, so we can try and get through some of these. What about people who have hepatic steatosis but they are not overweight?
Professor Simone Strasser
We do see that, it is called lean MAFLD, but it is still related to the same risk factors. It is usually people who are sedentary, who have terrible diets. We are seeing this increasingly in younger people, particularly with playing video games and sitting around eating pizza and chips and having a really terrible low protein, high energy, high carb, high fat diet, high sugars where they may not be particularly overweight on the scales, but they are carrying their weight centrally. If you carry it centrally, you carry it viscerally as well. That is lean MAFLD, and they are at particular risk of progressive liver disease and liver cancer. It is important to identify them.
Dr Natasha Feingold
Yeah definitely. Another question about the keto diet or the ketogenic diet. We see a lot of people who adopt that who are obese. Do you have any information about that?
Professor Simone Strasser
What is a keto diet? It is high protein, low carbs, low sugar diet pretty much. That is what the people should be having, and restricted eating is probably a good thing as well. The keto diet per se is where it is high fat as well. It is probably not ideal. The low fat version of the keto, but having protein and having protein as one of your key dietary inputs quells appetite. It is really important, particularly in people using GLP-1, as you know, they must have their protein or they could get sarcopenic from muscle wasting. Protein is really, really important. I am not so convinced that the fat component of a true keto diet is important, and I think it is probably harmful. Getting the sugar particularly out of the diet is really, really important. Some people do that with restricted eating and whatever. Whatever is sustainable and really what I think in these patients is it is not about a diet per se. It is about a complete lifestyle change and that they can sustain going forward and maybe hopefully even enjoy and get them away from the snacks and the takeaway food and all the other stuff.
Dr Natasha Feingold
Somebody has mentioned also in the chat about RPA has a lifestyle medicine clinic that sounds pretty amazing with one on one consults. For anybody in the area that might be a good place to refer to. The other question we had was around histology, when you do a liver biopsy for hepatic steatosis, are you able to differentiate between alcoholic or alcohol related liver disease and other forms of liver disease?
Professor Simone Strasser
I guess the question is when do I do a biopsy? It is not that often, but I have done some recently in younger people and particularly in people who are not particularly overweight where I cannot figure out their cause of liver disease through serology testing for autoimmune diseases, for viruses. I do a FibroScan. Not only on FibroScan do we get the fibrosis assessment, but nowadays we get something called CAP or controlled attenuated parameter which also tells us the fat content of the liver. That is a number. It is really useful. If I do a FibroScan on somebody and I get a CAP score in the 300s, that person has got moderate to marked steatosis. I may not do a biopsy, but when it is less and I am not sure what is going on, I will do a biopsy or if I am worried that there is another driver of liver disease. On liver biopsy, we will see steatosis but we will also see inflammation. There are overlapping features between severe metabolic associated steatohepatitis and alcohol related steatohepatitis. They can both have something called Mallory's hyaline which is this hyaline, reddish sort of deposits in there. They can both get ballooning of hepatocytes showing really hepatocyte sickness. They can both have inflammation. There are significant overlapping features in the more inflammatory form of MAFLD, which is MASH and the inflammatory form of alcohol related liver disease or alcoholic steatohepatitis. They can certainly overlap. That is why it has been so great to have access to this new PEth test because that helps figure out what might be the main drivers in patients that are underestimating or underreporting their alcohol intake.
Dr Natasha Feingold
Yeah, definitely. Are there any particular LFT patterns that you see that would suggest autoimmune liver disease or more rarer forms of liver disease?
Professor Simone Strasser
It depends on what we are talking about. Primary biliary cholangitis used to be called primary biliary cirrhosis will be particularly cholestatic liver disease. Particularly high alkaline phosphatase and GGT. In alcohol, you will just see the GGT. You will not usually see the alkaline phosphatase as well. That would be unusual to get very high levels just in fatty liver disease. In autoimmune hepatitis, usually the transaminases are particularly high, particularly in the more severe forms of autoimmune hepatitis. There are other causes. There is Alpha-1 antitrypsin deficiency, there is Wilson's disease and all these other things that if things do not feel quite right for this is just due to their obesity or diabetes, then they should have a full liver screen as well and most GPs I think are doing that.
Dr Natasha Feingold
Now what about hepatitis B vaccines? Would you be able to answer some questions about that? We see people that do not respond to their course. Is there anything as a liver specialist that is recommended?
Professor Simone Strasser
I always get that question. I would refer to the Australian Immunisation handbook. There are some recommendations there about re-vaccinating and about an accelerated protocol. Some people still, after repeated vaccination, just do not get antibody. Then we think they are at risk if they are exposed to hepatitis B. Now the only way you get exposed to hepatitis B is through injecting drug use or more importantly, sexual transmission as an adult. If they are not at risk, then it would be less stressy. If they are a healthcare worker, it is a problem if they do not seroconvert after vaccination. If you have a needle stick exposure from somebody who has got hepatitis B, then in that setting, you have got to be treated as being at risk, I think.
Dr Natasha Feingold
What about for people who are non-converters, is there any possibility that they have some immunity or if their serology is low?
Professor Simone Strasser
I think we do not really know the answer to that. A very important thing is and we sometimes see this is that people will have vaccination, then they will be tested for surface antibody and never seroconvert, but they are actually living with chronic hepatitis B already. That is why if you do hepatitis B testing, do all three tests because then you will find the ones and there are some people who have got occult hepatitis B where their surface antigen is negative, their surface antibody will be negative, but their core antibody will be positive. They may actually even have a low level of viremia. Making sure you have got all three assays done will help you understand they are not seroconverting because they have actually been exposed to hepatitis B itself. They are just not surface antigen positive or they may be surface antigen positive and you just never tested for it.
Dr Natasha Feingold
What about statins with people that have MAFLD? Is there anything we have to be aware of with that?
Professor Simone Strasser
Yes, they all need it. Everyone is worried about using statins in patients with liver dysfunction or that it may be a significant cause of liver liver damage. It is very rare that statins cause liver injury. Of course, if you start anyone on any drug and suddenly the next time you do a blood test, their ALT is through the roof, then you have got to worry that that is a drug induced liver injury, but it is incredibly rare. As I said, the reason people with MAFLD die is from cardiovascular disease. Statins are really, really important for patients. There is emerging evidence that statins may have a role in reducing the risk of liver cancer and also reducing portal hypertension and their studies evaluating statins in patients with portal hypertension because it has got favourable benefits. There are just so many benefits to statins in this population regardless of their stage of liver disease even preventing their cardiovascular death and cerebrovascular disease and everything else and also maybe preventing some poor liver outcomes that they are really indicated in patients who have hyperlipidaemia. I do not think they are indicated in the absence of a lipid indication, but most of these patients will have a lipid indication.
Dr Natasha Feingold
Is there a target LDL that you aim for in general?
Professor Simone Strasser
According to the cardiovascular guidelines.
Dr Natasha Feingold
I think we might be wrapping up. I know there are quite a few more questions, but I do not think we are going to be able to answer all of them. I am sorry to say. It was amazing to have you here, Professor Strasser. Thank you so much for all that information. I know we are going to use all the the lecture slides you have sent us and refer to them many times over because they are so helpful, and we see so much of this in general practice. It was a really, really helpful webinar today and we will be sending out all the slides and the resources, and I am sure there are ways for us to to get the further questions answered. I know there is quite a few burning ones that are a little bit more specific to cases, so hopefully we can get those answered somehow. We really appreciate your help tonight and your talk tonight. Thank you very much.
Professor Simone Strasser
It has been an absolute pleasure. Thank you, everybody for your attendance.
Dr Natasha Feingold
Thanks. I will hand it over to Serena.
Serena
Thank you. I would just like to thank Simone and Natasha once again for presenting and to everyone who joined us online. We do hope you enjoyed the session and that you also enjoy the rest of your evening. Thank you and good night, everyone.