Hepatitis B in General Practice
Serena
Good evening everyone, and welcome to tonight's webinar hepatitis B in General Practice. We are joined tonight by presenters Dr Caran Cheung and Associate Professor Ken Liu. My name is Serena and I am 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 and Torres Strait Islander colleagues that have joined us online this evening. Now I would like to introduce you to our presenters. Dr Caran is a S100 hepatitis B and HIV prescriber. She works in general practice in Sydney and has a special interest in sexual health, viral hepatitis and addiction medicine. She is a clinical editor at South Eastern Sydney Health Pathways and enjoys providing education to other GPs. We have also got Associate Professor Ken is a clinician scientist and staff specialist transplant hepatologist at the Australian National Liver Transplant Unit, Royal Prince Alfred Hospital. Prior to becoming a consultant, he spent a year overseas as the hepatology fellow at the Chinese University of Hong Kong, seeing patients with chronic hepatitis B and conducting research in this area. He regularly teaches GP HPV prescribers and has been involved in writing national and international guidelines on chronic hepatitis B, liver cancer and liver transplantation. I will now pass it Caran to go over the learning objectives.
Dr Caran Cheung
Thanks, Serena. I am just going to share my screen. The learning objectives for this presentation would be around identifying opportunities for testing hepatitis B for people at risk, and also identifying people who we would encourage to have hep B vaccinations. We would also like to summarise what is our role as GPs and primary care clinicians in identifying, diagnosing, monitoring and treating people with chronic hep B, and lastly, to explore what are the tools and decision support pathways and also referral pathways for people with hepatitis B. Thanks also Ken, for coming to join us tonight and lend his expertise. Ken will be monitoring the chat box as we go along. If you have any questions, feel free to shoot them over and he will answer, and also we have Question Time at the end as well. Even though we cannot hear or see you, I want to make it as interactive as possible.
A bit of background about hepatitis B virus. It is a bloodborne virus or bloodborne infection that infects the liver and can cause liver injury, and as we know, there can be a cascade of effects there. From the initial liver injury that could lead to fibrosis, it could lead to then cirrhosis and which can increase someone's risk of developing hepatocellular carcinoma or liver cancer. It can be acute or chronic with hepatitis B that is defined as anyone with six or more months of infection would be defined as chronic. The group who are chronic are the ones where we as GPs will be most involved with in terms of long-term monitoring and also monitoring while people are in treatment. These people would typically be life-long so-called carriers of infection, I suppose back in the day when we used to use that term, but we do not like to use that term anymore because it implies that we are not really doing anything active, but in fact, we should be actively monitoring and treating these patients. We know that most people live with chronic Hep B infection, have acquired it at birth through vertical transmission or in early childhood through horizontal transmission. It is certainly in Australia, 70% of people living with chronic hep B were born overseas. Lots of people are from our migrant communities, and as we know, Hep B is a vaccine preventable illness especially in people who have not had a history of chronic infection. They are eligible to receive the vaccine, and it has been part of our national immunisation program for infants since 2000 in Australia. The unfortunate thing about hep B is we still have not found a cure for it, unlike hep C, which is easily curable with direct acting antiviral tablets nowadays, but hep B is still incurable and so the aims of treatment are to limit liver injury, and then in turn that would prevent liver disease and cancer. There is also a guideline that has been recently updated and Ken I think it is the 2022 GESA guidelines that provides that consensus statement. Just move on to a little bit more information about this disease. As we know from teachings that this is easily transmissible and there is four ways of transmission, perinatally or through vertical transmission from mother to child at around the time of birth. That is commonly the most common cause of transmission, and then there is also parenteral routes, percutaneous routes, such as from say needle sharing or from tattoos from places where they do not have good procedures for decontamination. Blood transfusions as well in certain countries where they do not have ways of screening for hepatitis B and sexual transmission. This is less common as is parenteral or percutaneous transmission in Australia. Both of these routes are less common, but we do see them and the other one that is there are horizontal. We talked about horizontal transmission through early childhood physical contact such as child to child if someone has a mucosal break in the skin and then is in physical contact with someone else who has a break in their skin, and that is another common route of transmission, but it is really important to debunk some of those myths as well. Sharing food and drinks for example, is not a risk for hep B transmission. As GPs, we probably should share that role with education and debunking those myths, and it is also important to remember that most of our clients who are, for example, from Asia, where infection is highly prevalent. Most of that transmission is from perinatal route or from close contact during early childhood through horizontal transmission, but in areas where we have low prevalence so that includes like Australia or New Zealand, then transmission typically occurs in people who are at risk whose lifestyle put them at increased risk, such as from sexual activity or use of contaminated injecting equipment.
With regards to vaccinations, we are all very familiar with the Australian Immunisation Handbook, which recommends hep B vaccination for all infants and also particular groups would be perceived to be at risk. These include Aboriginal or Torres Strait Islanders, people who are immunosuppressed people with certain medical risk factors such as if they have already got infection with hepatitis C or HIV or chronic liver disease or developmental disabilities, people whose occupation increases their risk of acquiring hep B, anyone who is performing exposure prone procedures such as us, any employment that involves direct patient care including nursing staff and clerical staff in hospitals handling human tissue, blood or body fluids or handling needles and syringes and anyone who is travelling or intending to travel to hep B endemic areas may be at increased risk, and people whose circumstances increase their risk of acquiring hep B, migrants from hep B endemic countries, people engage in sex work, people who inject drugs, MSM or anyone who is a household contact or sexual contact with someone with hep B. The full list is available in the AII handbook, but in New South Wales there is on top of the catch up vaccination program for people up to the age of 19 if they miss out through universal vaccination in infancy, there is also free vaccinations for certain people, and for each state it is different what each state would be subsidising, but in New South Wales, the hep B vaccine is free for anyone who is Aboriginal or Torres Strait Islander, any household or sexual contacts of acute or chronic hep B cases, anyone who is immunosuppressed as we have said, people with HIV or hep C, MSM sex workers and anyone who goes to a local public sexual health clinic at the LHD's discretion may receive these vaccines for free as well. I have just put the link there on the slide.
This is a bit of a map showing the pattern of hep B prevalence. It quite nicely highlights areas of high prevalence as we can see which is Western Pacific area. That includes the Pacific islands and certain parts of Asia which we have lots of migrant communities from and also certain parts of Africa as well. Those are the ones in red and orange on the map, and in 2019, there has been an estimated 316 million people living with chronic hep B infections. That is actually quite a big figure, and the grand scheme of things but the main thing to take away from this is that lots of our patients are migrants from these high prevalence areas. We need to have that cultural awareness when we are seeing these patients, and in fact, there is some really good cultural awareness training courses available as well through organisations such as I think ASHM runs some of the course content through their online education modules, but there are also formal courses you can take through your PHN. In terms of hep B prevalence in Australia, every few years ASHM does a viral hepatitis mapping project alongside I think it is. Burnet Institute in Melbourne. They typically do a study to try and examine what other regional variations in the prevalence and what is the uptake in care as well or uptake in treatment. That is where these statistics have come from. 72.6% of people living with chronic hep B in Australia were born overseas. The vast majority of those were from China and Vietnam, 18.5% and 10% respectively. Of the 30% of people living with chronic hep B were born in Australia, 6.7% were Aboriginal or Torres Strait Islander and 3.6% were MSM and 2.7% were people who inject drugs, and unsurprisingly, the highest prevalence in New South Wales is amongst Southeast Asian born migrants. If you would like to take a look at the statistics in a bit more detail, just click on that link referenced in the slide on the Viral Hepatitis mapping project. I think his GP is the most useful thing for us during a consultation is knowing where to find the information. Obviously, everything from this talk tonight, there is a lot of information in there and I think not knowing all of it is absolutely fine, but it is all about when you are consulting someone with hep B, where do I find the information I need to know what to order for testing, know who to target for testing, how to interpret the serology, and what should I do in terms of referral pathways. There is a really great tool here. Maybe Serena can put it in the chat box so everyone can download it and take a look. It is in a PDF format, which is really great, and before COVID they used to hand out these paper version cardboard things. It is like a flip chart. What you could do is print it out and then laminate it, and you can have a little flip chart as you go along when you are consulting. I find that quite useful, otherwise PDF on your desktop. We will just go through them one by one the categories there. That is the first page of the flip chart. When to test. We will go through that now. Obviously, anyone who comes in asking for testing could be offered testing, but then there is also groups of people who are in these high priority groups who are at risk, and we should opportunistically think about targeting for testing. That would include people born in these intermediate or high prevalence countries. From the map that we showed at the beginning with the global prevalence to try and identify these people and think about offering an interpreter if necessary, especially when you are seeking pre-testing counselling, and Aboriginal and Torres Strait Islander people, anyone undergoing any immunosuppressive treatment because of the risk that if they did have any resolved hep B infection in the past, there is a risk for that virus to reactivate. Anyone who is pregnant, it is part of our antenatal serology, especially for people who are aware that they have been doing antenatal shared care. That is part of our testing for most LHDs. Any infants and children born to mothers who have hep B. We would like to test the serology for them at least three months after they finish a four dose vaccination course. Typically, that would be from 9 to 12 months, and anyone who looks like potentially physically on examination looks like they have chronic liver disease, anyone with an elevated ALT and alpha fetoprotein of unknown cause, and any health professionals who perform these exposure prone procedures, any partners or sexual contacts or household contacts of anyone with hep B infection, anyone who has ever injected drugs and MSM and people with any multiple sexual partners, people who have ever been in any custodial settings or people who have HIV infection or hep C infection, we should have a look for hep B as well. Co-infection typically means that the care may be slightly more complex or our treatment options may be slightly different. Anyone who is undergoing dialysis. With patients undergoing dialysis, they themselves are slightly immunocompromised, but also there are certain molecules sometimes that the dialysis machine pulls out and does not pull out and I think Ken back in the day, back many years ago, I think there were some people who acquired hep B from dialysis. I am not sure nowadays whether that has changed, and anyone who is a sex worker, anyone initiating prep, as we know, there is prep guidelines which tell us what baseline tests to do and hep B, hep C and those are all part of it as well. I think the main thing is when we are thinking about offering testing is to think about informed consent and think about pre-test counselling, and in doing so think about whether we need to use an interpreter professionally in order to for there not to be any misunderstandings. For example, once you have acquired someone's informed consent, then to make sure that they have the capacity to understand the results as well. In English, if you have any doubts, then use an interpreter. In terms of ordering the tests, this ASHM decision making tool talks about ordering all three tests at the same time. We should enter in surface antigen core antibody and surface antibody, and the reason for that is because we will see on the next slide with interpreting serology. This is really important. If we do not order all three of these tests, then we do not actually know what type of infection they have or whether they have infection, whether they are susceptible or whether to vaccinate. So, if we did just write, hepatitis B serology on the testing slip, it would not give us all three tests typically. Say, for example, you wrote hep B serology on the request form with Laverty, typically it comes back with the surface antigen and then the surface antibody, but it does not come with a core antibody. You do not actually know someone's true status unless you have ordered all three, and it is Medicare rebates for all three tests. If you write something like ‘query chronic hepatitis B’ on the pathology request form. This is the gnarly part, I suppose, for most people where they look at this and it is just a bit of information overload, but really it is not too difficult because it is exactly as it is outlined here. If it is all so negative with the surface antigen core antibody surface antibody then someone's susceptible of infection if they are exposed. The second one, if they are surface antigen negative but their core and their surface antibodies are positive, that means that they have had infection that is resolved. The surface antigen is negative means they currently do not have infection. Then the third scenario surface antigen is negative. Core antibody is negative and surface antibody is positive. If the surface antibody is positive that means that their immune through previous vaccination. Again, in this scenario surface antigen negative saying that they do not currently have hepatitis B and the core antibody is negative. They have never had it before, but if their surface antibody is positive then it is from vaccination that they have got immunity. Then the next two scenarios are for people who have hep B infection. As you can see the surface antigen is positive in number four and number five here. The difference is that the IgM core antibody is positive in people with acute hep B infection. And Ken do you know how long it takes for this IgM antibody to be negative after someone has had an acute infection?
A/Prof Ken Liu
Like many weeks later, we use it. One of the questions in the Q&A is what is the value of it? but we use it all the time to determine if someone has got acute hep B or a chronic hep B basically.
Dr Caran Cheung
Awesome. The fifth scenario is the one that says chronic hep B infection. That is the one that will see most of this in terms of chronic disease is the ones who have chronic hep B infection. The surface antigen is positive and the core antibody is positive but the surface antibody is negative. Then the last scenario is a little bit of a tricky one, and that one is the one where we should think about referral or think about seeking advice from a specialist. It is when the surface antigen is negative but the core antibody is positive, but the surface antibody is also negative. There is a lot of different possibilities there. There could be this thing called occult HPV. Occult hep B is tricky because they could have a very low-level viremia, and they actually have hep P or it could be that it is resolved hep B or it could be, for example, they are developing it or I do not know, Ken, is there some guidance around this scenario where you have just got a core antibody positive? How should GPs approach this?
A/Prof Ken Liu
I think this is really tricky. Whether you are a GP or a specialist because there are multiple possibilities, and this is because antibodies wane, for example, the number two on your list, over time your surface antibody wanes to be undetectable, therefore you look like just an isolated core and antibodies are not perfect, you could get a false positive core, that is another option. I think the main thing to rule out is an occult hep B, in which case these patients would have positive DNA despite having a negative surface antigen, and the only way to deal with that is through ordering a DNA, but again that is difficult because when your surface antigen is negative and you order a DNA, the patient has to pay out of pocket for that. It is not available.
Dr Caran Cheung
If they referred to the public hospital, is it free?
A/Prof Ken Liu
Yeah. When I order it, our hospital does not charge. We could sometimes mistakenly order two DNAs two days in a row and hospital does not care. The easiest thing is probably just to ask a specialist, what would you do in this situation?
Dr Caran Cheung
I think the health pathways, your local health pathways would have a page there about seeking hepatology or gastroenterology advice. You do not necessarily need a formal referral if you feel like it is something you just want advice on and it may connect to your local gastro registrar who can answer that question or they can talk to their boss to do that.
In terms of the next step, if we have established that someone has surface antigen positivity, then this tool is really great. It tells you should order these the following tests. That includes an E-antigen and E-antibody, and it is important later on as we will see on the next slide because that is important to stage the disease to see which phase of infection that person is in, and then also we want to do a HPV DNA quantitative level. That is also important to assess the phase of infection and the full blood count, liver function tests and INR, those three things are very important as well. They can look for the synthetic liver function, but also the LFTs would tell you about the degree of liver injury from looking at the ALT level and AST levels and the alpha fetoprotein and the liver ultrasound are useful for looking for a tumour. Essentially, you just want to do this at baseline, just make sure that they do not have a hepatocellular carcinoma, but also the liver ultrasound can sometimes tell us if there are any other structural abnormalities with the liver, whether there is any fatty liver disease for example, and it is also really important to do some fibrosis assessment at baseline so that could be a Fibroscan which is thought to be the gold standard, but if you do not have access to a Fibroscan, you could do an APRI score, which is the AST to platelet ratio index, and there is also other fibrosis scoring such as the FIB-4 which is the AST and the platelets, and then you add on the ALT and the age. These calculators are all online if you Google it. It is just the first two links on Google. There are the University of Washington calculators which are really good, and also MDCalc is okay as well, but in addition to that we would like to check for co-infection as well. Hep A, hep C, hepatitis delta virus and HIV. Hepatitis delta virus is a co-infection with this virus, which can only occur in someone who has already been infected with hep B. It is essentially a more severe form of viral hepatitis that is more likely to progress to cirrhosis, and therefore increased risk of hepatocellular carcinoma. Should also evaluate for other comorbidities, alcohol and other drug use, diabetes, fatty liver disease and anything else as well, and try and address that and then educating our patient about the importance of screening for household contacts and sexual contacts and encouraging them to get vaccinated if they are not immune to hep B infection, and I guess there is no hard and fast rule about how often to check the serology of these household contacts or sexual contacts, but typically the guidelines say to check regularly. Again, in that situation, would you ask them to check once a year or what does regularly mean for GPs?
A/Prof Ken Liu
I think if the household contacts have surface antibody through vaccination, they are protected even if they get exposed. I would not keep checking, and then if for whatever reason they either are anti-vaccine or they are a non-responder then I think once or twice a year is reasonable.
Dr Caran Cheung
Thanks for that. It is important to remember that Medicare does cover at the HPV DNA testing once a year for patients not on treatment. The ones who are being monitored for the hep B and people who are on an antiviral treatment for hep B, they are entitled to it four times a year. The Medicare is a bit specific though, like a 365-day thing. If you order it one day too early, they do charge the patient. In terms of the initial assessment, it is important to think about when to refer for specialist advice or specialist care, but vast majority of people with chronic hepatitis B are managed in primary care actually, and only a very small number need to be referred. These are the situations in which we might consider referral. Anyone with acute hep B infection, anyone with co-infection because that is quite complex, anyone with HIV, hepatitis C or hepatitis D virus co-infection, anyone who is pregnant we would like to refer early in their pregnancy care in the first trimester, and anyone who is immunosuppressed, anyone who has ever been treated with any different hep B medications before. In Australia, the commonly used ones entecavir and tenofovir are available on PBS, but there are some people from other countries, I have had some patients who are Indonesian, for example, and they have been on lamivudine, which is a very old antiviral medication that we used to use for hep B treatment decades ago, and that has been associated with some increased resistance. We are worried about resistance, and also we would like to know about the history of antiviral use, and what the results have been like. In that situation, it is a bit more complex we would like to refer and if we are suspecting any a liver mass say, for example, you have done a liver ultrasound and it says there is a 1 cm mass and it does not really know what it is, then anything like that needs a really urgent referral to a specialist. Anyone with cirrhosis. Anyone with end stage liver disease should be referred to a specialist. And Ken, do you have anything else to add to that list, any other referral criteria?
A/Prof Ken Liu
No, that covers it, but I think it would be useful for me if you pick up a mass on an ultrasound, then do not send the patient to me with an ultrasound like order a multiphase CT scan. Then it is like one step along and I can bring that scan to an MDT, whereas, it just it just hastens things if that happens.
Dr Caran Cheung
We order a four phase CT scan of the liver with a portal venous phase, arterial phase. I forgot the other phases.
A/Prof Ken Liu
Third phase in a non-contrast. You do not even need to know it is quad phase, just write multiphase CT. Most radiology places will do four phases.
Dr Caran Cheung
Okay. On the other side of the decision making tool, the second page and there is only two pages on that chart. The second page talks about the phase of infection. Once we have determined someone has chronic hep B infection, the infections being present six or more months, then this is what we look at. As you can see, the nomenclature has changed and that has reflected in those 2022 visa guidelines, but we used to call these phases of infection, the top row of the table, immune tolerance, immune clearance, immune control immune escape. The second row there is the updated terminology, but you can use them interchangeably. People will understand what you mean. E-antigen positive chronic infection, E-antigen positive chronic hepatitis, E-antigen negative chronic infection, E-antigen negative chronic hepatitis and so the first two phases, E-antigen positive and second two phases E-antigen negative, and then it is split between chronic infection or chronic hepatitis. The difference being that in hepatitis states, the LFT is raised. There is a risk of liver injury. Therefore, they are at increased risk of developing cirrhosis and hepatocellular carcinoma. Therefore, they would benefit from treatment. In those two phases of infection, we would like to refer them onwards to either an S100 community prescriber who could be a GP like you or me or a specialist. Feel free to hone in on that chart on the right-hand side there because it does have a bit more detail about how the ALT elevation, the levels are very different to our normal lab levels, as you can see, for a man, if it is over 30 then it is considered elevated, but for a woman if it is over 19, that is considered elevated already. That is the difference in between the lab reference is for women. We use ALT over 19 as the cut off, and the other thing is that the E-antigen positive chronic hepatitis phase and the E-antigen negative chronic hepatitis phase, the HPV DNA levels are a little bit different there. If it is over 20,000 for that first phase where we used to call it immune clearance and over 2000 for that phase which we used to call immune escape. As we can see, the management is quite different depending on the phase of infection the patient is in, but everyone, regardless of which phase they are in, needs regular monitoring, and if we do not regularly monitor them then we do not know if they have changed phase because it is a dynamic process. You can move between phases. Ken, a question for you. I thought if we had met a patient for the first time who has not got a history of any hep B serology, they test surface antigen positive, then would you schedule another blood test in six months before you deem that they have chronic hep B? Or like how should we approach these patients in primary care?
A/Prof Ken Liu
I think it depends, for me I personally would not but because by the time they see me it is quite clear that it is chronic. Whereas I think it depends on the clinical scenario. If you have got, for example, someone who is born in Australia for some reason maybe missed vaccination and their IVDU and then they have had a recent transaminitis and then you find that the surface like this, they have clearly just had an acute hep B and then those people are definitely recheck it to make sure they do not go on to chronic, but again, if you have someone from Asia with their mum has got hep B and they have turned up with that, it is almost certain that they have got it vertically transmitted and they have chronic hep B.
Dr Caran Cheung
In summary, our role as GPs, we will be doing the regular monitoring but it is a negotiation between people. Even though we are referring to say a specialist or S100 prescriber, it is not necessarily that they will take over care of your patient. It might be a quite a shared collaborative approach just like antenatal shared care for pregnancy. You got to work out who does what, but the GP is more than capable of monitoring any patient, whether they are on treatment or off treatment, and then potentially that when they see the specialist or S100 prescriber once or twice a year or that blood work would be done already, and so they maybe just be prescribing and looking over things, and then the other part is the lifestyle management as well. For most people looking after these patients, we are thinking about ordering an LFT regularly that could be every 6 to 12 months if they are stable, E-antigen, E-antibody and HPV DNA level, but the most important thing is to do HCC surveillance for these patients, which includes ordering a liver ultrasound plus or minus and alpha fetoprotein, which has a little bit become controversial, but definitely a liver ultrasound, and we will talk about the people who meet criteria for HCC surveillance as well. This slide here just talks about the ongoing monitoring that we talked about before. If someone is not on treatment then six monthly LFTs and E-antigen antibody every 6 to 12 months and HPV DNA every 12 months, and also to think about the fibrosis assessment every 12 months as well. In summary, not everyone needs treatment and treatment is dependent on that phase of infection. The most important thing is monitoring and monitoring to prevent progression to cirrhosis and liver cancer. In terms of HCC surveillance, there is a nice box at the bottom of that tool, that decision making tool that concisely list the people you would be considering for HCC further surveillance. That is anyone with cirrhosis, anyone who is 40 or over with a family history of HCC and also thinking about how old was the person in the family who got diagnosed because you want to start screening ten years prior to that earliest case in the family. Of note, sub-Saharan Africans, anyone 20 years and over needs to start HCC surveillance. Anyone Aboriginal or Torres Strait Islander would be 50 years and over, and if they have got high risk features, then it will be 40 years and over, but in terms of Asians or people from Pacific Islands, if you are a male 40 years and over, if you are female 50 years and over.
We will just hop on to some case studies now. First case study. I might just read through the case and then I will get Ken to comment on some of the questions and answers as we go along. First case study is a 67-year-old woman. She has moved from Hong Kong to Australia 18 months ago. She is living in Sydney with her husband. She was diagnosed with hep B during antenatal testing when she was 27 in Hong Kong, and she has been under monitoring with annual blood tests and annual ultrasound examinations. Her last ultrasound was 12 months ago and she has never been treated with an antiviral medication. In terms of family history, she does have a brother with chronic hep B and history of hepatocellular carcinoma, and her sister also has chronic hep B. She also has a son who is 40 years old and has chronic hep B but not monitored, living in Sydney. She has got no really significant past medical history. He is very apart from above, a healthy weight, maybe she is slightly overweight but does not drink, does not smoke, does not take any other regular medications. In terms of the blood tests, ALT was 49. Remembering that over 19 is considered elevated for females, AST is 42, bilirubin is 14, albumins 41, platelets 245, AFP of 2. Surface antigen is positive and E-antigen is negative and E-antibody is positive. Her HBV DNA level is 6 log10. Ken, actually, sometimes I am a bit confused about these readings, the log10 scale and so forth, and considering that the ASHM decision making tool has the cut off as 20,000 or 2000 International Units per mL. How do I interpret this result in terms of the DNA level?
A/Prof Ken Liu
It has been hard because we have it has been so long since we have all done high school maths, but the easiest way to do it is with the bit that is not in the brackets. 1.09 and then it goes times ten to the power of six. That means 1.09 and then you move the decimal point six places to the right, so that ends up being 1,090,000. That is my DNA, but if you have an iPhone, you can do the log bit if you want. If you just need to use the scientific bit of the if not the just the common calculator, but you can get a more advanced scientific calculator and you can work out what 6.04 log10 is, but I think the easiest thing is ten to the power of whatever is, you add that many zeros at the end of the number before the decimal point.
Dr Caran Cheung
We should probably have superscripted that six. Apologies, everyone, so then she had a Fibroscan done and it shows that her KPA was 8.4. Looking at that, there is also when you do a Fibroscan, there is a chart that shows you this is the validated numbers for this disease state. For this condition of hep B, these are the cutoffs that would signify significant fibrosis, severe fibrosis cirrhosis, and it is different for every condition. We need to find the specific chart for that condition, but in her case 8.4, that means that she would be in that range of significant fibrosis or F2. Ken, what phase of hep B infection is she in?
A/Prof Ken Liu
She has an elevated ALT. She is e-Antigen negative and e-Antibody positive and the DNA is high. This puts her in the e-Antigen negative hepatitis column which we used to call immune escape.
Dr Caran Cheung
Okay. Is antiviral therapy indicated?
A/Prof Ken Liu
In general, anyone with a high ALT and a DNA that is elevated above 20,000 in the e-Antigen positive people and above 2000 in e-Antigen negative people, they would qualify for antiviral therapy because the liver is being inflamed and the longer you leave it, the more fibrosis accrues and they end up with cirrhosis if left untreated.
Dr Caran Cheung
Yeah. That is all on the second page of that ASHM decision making tool. You have explained perfectly why she should be treated. In her situation, is HCC surveillance indicated? If so, how should that be performed?
A/Prof Ken Liu
It is definitely indicated and for multiple reasons. One is she is Asian women over the age of 50. That puts her at risk of HCC such that it is cost effective to do HCC surveillance. Secondly, she has got a family history, first degree relative with HCC. In most guidelines, it does not matter what your age is. If you have a first degree relative with HCC, you should start HCC surveillance. There are at least two reasons why she should have HCC surveillance. She is having suboptimally, I would say, every guideline says you should do it every six months with ultrasound with or without AFP. Most hepatologists order AFP along with the ultrasound. You might not know why that is or the audience might not know. Generally, we give the doubling time of a liver cancer around five to six months. Every half a year, a lesion would double. The sensitivity of an ultrasound picking up a lesion under 1 cm drops significantly. Let us say, you come across a patient with a 0.9 cm HCC and you miss it on the first ultrasound, you repeat it six months later, the lesion doubles to 1.8 cm. We still consider that very early HCC, very curable with surgery or ablation etc, but you do not do it 12 months later and it doubles again to 3.6 cm, almost 4 cm. That now becomes a bit more cumbersome to treat and the treatment options may not be curative. This is the reason why if you are going to do it properly, you should do it every six months, not every 12 months.
Dr Caran Cheung
Makes sense. Would you consider screening her husband for hep B infection and how would you recommend her son be monitored?
A/Prof Ken Liu
Definitely, if her husband is not immune, I cannot remember if he was. He should be screened. The son who has hepatitis B, you have got to firstly work out what phase of infection he is. If he is not in one of those that need treatment, I would see him every six months with blood tests, and because he is Asian at age 40, he should also start HCC surveillance. Every six months, I will see him with an ultrasound and blood test.
Dr Caran Cheung
Perfect. That summarises that case. We will move on to next case. A 29-year-old woman, born in Vietnam, moved to Australia with her family when she was 12 years old. She is currently 12 weeks pregnant with their first child and has attended your practice for routine antenatal screening. Family history is that her parents and brother both live in Sydney. She has got no really other significant past medical history. Her blood test showed that her surface antigen is positive, however, and hep C serology and HIV serology are both negative. Does she have hep B?
A/Prof Ken Liu
It means you hep B.
Dr Caran Cheung
Does she have acute or chronic hep B?
A/Prof Ken Liu
This is the situation I was telling you about before where I would not repeat this lady's serology six months later just to prove that she has chronic hep B. The surface antigen is positive. She is from a high prevalence country. I would just assume she got perinatally transmitted hep B as a child.
Dr Caran Cheung
What do we want to know about her hep B status?
A/Prof Ken Liu
With any hep B patient, you should figure out what phase of infection they are in. Particularly for pregnant women, you care about how high their DNA level is because on top of her baby getting hepatitis B immunoglobulin and the vaccine, if her viral load starts off very high, then she would qualify for antiviral therapy to bring it down in the third trimester to absolutely minimise that risk of her baby getting hepatitis B perinatally transmitted.
Dr Caran Cheung
The whole point is to prevent this perinatal transmission. What are the implications of being surface antigen positive? I think you have pretty much answered that already. She has had some further testing. E-Antigens positive, e-Antibodies negative, HPV DNA 8 log 10 and ALT is 15. That correlates to that phase of infection. E-Antigen positive chronic infection in the immune tolerance phase. She has got high levels of HPV DNA. The question is what are the implications of being surface antigen positive in pregnancy? I think you answered that about the increased risk of transmission to the infant especially if she has got a high viral load. I think for us as GPs, it is important to remember that regardless of the viral load, any baby born to a mother whose surface antigen positive, should receive hep B immunoglobulin pretty much immediately after birth, and then they should receive the whole four dose vaccination course with follow up serology. That is where we will come in to organise that follow up serology for the infant as well three months after they finish that course of vaccination. Pregnant women with hep B are at risk of transmitting hep B to their babies. Increased risk if they have high viral loads of over 200,000 IU/mL. As Ken alluded to, they do require treatment in the third trimester of pregnancy and that is typically about week 28 of pregnancy. Is that right, Ken?
A/Prof Ken Liu
That is right.
Dr Caran Cheung
Regardless of viral load, babies born to surface antigen positive mothers will receive hep B immunoglobulin vaccination and follow up serology. The other thing is about postpartum care. Ken, with this, how should GPs manage and monitor for these postpartum hepatic flares and when should we refer back to a specialist?
A/Prof Ken Liu
Usually you would continue the antivirals for about up to a month after the baby has been delivered and it is expected that during the first three months postpartum that there will be a slight blip in the liver function tests due to a postpartum flare. This is almost always not serious, and you would just keep monitoring the LFTs until it all resolves. If it is not resolving or it is getting worse, then you should refer to a specialist.
Dr Caran Cheung
Would that be after 12 months postpartum or how many months should we define that?
A/Prof Ken Liu
If it was going on for more than six months, I would refer to a specialist, especially since there might be a waiting period to get the patient seen.
Dr Caran Cheung
Okay. Thank you. We have also got here the websites. You can find prescriber for s100 community prescribers on there. Also, there is a great new tool that came out two years ago called the B-Referred website from ASHM which has some clinical decision making tools and referral templates as well. Here are some resources. Feel free to look into those a bit further. The other thing to mention is your local health pathways are really good resource as well, especially when it comes to the pages with local referral pathways. Which hospital, what is the information for sending referrals and who to contact for hepatology advice? I will just end it there and then Serena is going to take over now.
Serena
We have got about 5 minutes. We are happy to answer. There is one question in the Q&A box. Which one would you like to answer?
A/Prof Ken Liu
I have just been answering them as I have gone along.
Dr Caran Cheung
That is fine.
A/Prof Ken Liu
To summarise, there are a lot of questions on vaccination, especially in someone who does not have detectable surface antibodies. What would you do? I think in these patients you should always try and aim for them to have a level more than 10, so you can give a booster, and then if that does not work, then it is recommended that you repeat the initial three doses. The Australian Immunisation Handbook pretty much tells you what to do. It gives you good guidance on this. If someone, after two lots of the immunisation course, still does not mount a response. Then again it tells you what to do. If you have to check whether for example, if their core antibody positive, then you are never going to get a response from them because they actually have had chronic hep B exposed in the past. At the end of the day, if you cannot find a reason for it then it is just about harm minimisation.
Then the rest were mainly questions that we covered throughout the talk. One person asks if there are s100 prescriber but the hospital clinics tend to just keep these patients and how would they get access to patients because you need to do a certain number under guidance before you can be independent. There is nothing I love more than more GPs seeing my chronic hep B so that my clinics have room for other indications that cannot be managed by a GP. Every year you need to write a referral for the patient to come into the clinic. You can easily just write in your letter. By the way, I am now an s100 prescriber. Are you happy for me to see them instead? It has gotten to the point where in my clinic, I told you these patients should be seen every six months, especially if you are on HCC surveillance, you need ultrasound in six months. If you are not, you need blood tests every six months anyway. It has gotten to that point where I have now had to see these people yearly. Then when I see them, I give them two forms so that I rely on them to go and get the ultrasound and blood test in between. It has saved me clinic space, but either me or my nurse still have to chase those results to make sure there is not a new HCC. I would love it if more people became s100 prescribers. A lot of people are daunted by it, but it is actually not that difficult managing hep B.
Now there is a lot of questions. The cutoffs for DNA and ALT to define phases is based on trial data and also with biopsies where we know for example, if the DNA is in the immune escape phase is under 2000, then the reason for the raised ALT is unlikely to be hep B. That is why they have come up with that cutoff based on data from biopsies. What are the main side effects of antivirals? Like 99% of people tolerate them absolutely fine with no side effects at all, especially entecavir. With tenofovir, there is a small risk of things like renal tubular acidosis/Fanconi syndrome. You do get a tiny decrease in eGFR and bone mineral density over time, but they are not particularly clinically significant side effects. With entecavir, there is just about no side effects and is very well tolerated. Both of these drugs are renally cleared, so you do have to adjust them if someone has a reduced eGFR. Under 50, you have to go to second daily dosing, but they are very well tolerated. They absolutely are 100% free when you give an s100 form. There should be no reason why a patient cannot have antivirals if they are indicated. If a surface antibody is detectable, I would not do another booster.
The other thing is when it is under 10, does that mean that they will not be immune? That is not true either because you do have memory T cells that wake up when they get re-exposed to an antigen, so they could then mount an immune response again. Arbitrarily, we have used 10 as the cutoff where if it is under that you should give a booster.
Serena
Once again, I would like to extend my thanks to Caran and Ken 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.