Enhancing Hepatitis B Care and Prevention in Primary Care
Jovi Stuart
Good evening everyone and welcome to tonight's webinar Enhancing Hepatitis B Care and Prevention in Primary Care. My name is Jovi and I am your RACGP host for this evening. We are also joined tonight by presenters, Dr Caran Cheung and Associate Professor Simone Strasser. I have also just linked the hepatitis B decision making tool in the chat for you to refer to. Before we get started, I would like to make an acknowledgement of the Country. We recognise the traditional custodians of the land and the sea in 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 tonight. For me, I am dialling in from Guringai country, located in Sydney's North shore. I would like to formally introduce to you our speakers for this evening. Dr Caran Cheung is a GP and an S100 hepatitis B and HIV prescriber. Caran works in general practice in Sydney and has a special interest in sexual health, viral hepatitis and addiction medicine, is a clinical director at South Eastern Sydney Health Pathways and enjoys providing education to other GP's. Associate Professor Simone Strasser is Head of Department and Senior Staff Specialist at the AW Morrow Gastroenterology and Liver Centre, the Australian National Liver and National Liver Transplantation Unit at Royal Prince Alfred Hospital and the University of Sydney in Sydney, Australia. Simone is past president of the Gastroenterological Society of Australia and a board member of the Liver Foundation. Simone is a major clinical and research interests in viral hepatitis, primary liver cancer, fatty liver disease, advanced liver disease and liver transplantation. Simone is also current director of Hepatology clinical trials that IPAH leading clinical trials of new therapies for patients with hep B, liver cancer and other liver diseases. Many publications include many book chapters and over 200 publications in peer reviewed journals. So, welcome to all our speakers for this evening. I would just like to go over the learning objectives for tonight. By the end of this online CPD activity, you should be able to identify opportunities for hep B testing among at risk people and vaccination, summarise primary care clinician's role in identifying, diagnosing, monitoring and treating people with chronic hepatitis B and utilise hep B referral and clinical support tools. So with that, I would like to now hand over to Caran and We will start off the session. Thank you Caran.
Dr Caran Cheung
Thanks, Jovi. Hi everyone. Thanks for joining tonight. I am sure you guys are all pretty aware of what hep B is, but I guess we will just run through some of the basics again. So, hep B virus, HBV, we are going to shorten it to, is a blood borne virus that we know affects the liver, causes liver injury, and permanent damage can ensue. It can be either acute or chronic, and it is important we differentiate that and we will go through that in a bit more detail later on tonight. Most people living with chronic infection tend to have acquired hep B at birth or in the early childhood, and as we know, hep B is very vaccine preventable, and in Australia we have had a universal infant vaccination program since 2000 with a catch up program as well. We tend to offer vaccines to people who do not have chronic infection, but, later on I will ask Simone what do we do with other patients who have had resolved chronic infection. Hep B, unlike hepatitis C at the moment cannot be cured, but we know that we can limit the damage that it causes and prevent liver disease and cancer.
Next slide please, Jovi. Thank you. In terms of transmission, there are four major modes of transmission that is recognised, that is perinatal or vertical transmission from mum to bub or at around perinatal around the time of birth. There is also horizontal transmission which we know occurs through physical contact, for example child to child or from aunt to child, and there are also parenteral or percutaneous routes, this can be through say, for example, sharing needles or blood transfusions or tattoos or piercings, and then there is also sexual transmission as well, but I understand that with these routes of transmission typically especially sexual and parenteral that is less common in our setting, and we know that in areas such as Asia, here we have got on the slide Western Pacific region, which includes Asia, infection is quite prevalent there. In these high endemic regions, most of the transmission occurs perinatally or through early child contact, whereas in our setting in Australia, a low endemic region, so low prevalence, transmission typically happens amongst adults in those high risk groups through, say for example, parental routes or sexual transmission. Most people in Australia, however, given that we are a country of low endemicity, most of our cases come from migrants and Indigenous Australians who carry higher rates of infection in those priority populations. There are also some myths as well, for example, you cannot get hep B from sharing food and drink, or from touching someone with hep B. Those are not routes of common transmission or transmission at all.
We will move on to the next slide there. Yeah. Thank you. In terms of vaccinations, we are all familiar with the Australian Immunisation Handbook and it identifies that these people should receive vaccination. All infants as we mentioned through our universal infant vaccination program on the National Immunisation Program and Aboriginal and Torres Strait Islander peoples, anyone who is immunocompromised such as if they have HIV or anyone with any significant medical risk factors, anyone whose occupation increases their risk of acquiring hep B, for example, they are needing to perform exposure prone procedures such as if we are doing skin biopsies, for example, or suturing and any travellers to hep B endemic areas, and people whose circumstances increase their risk so that could be behavioural risk related such with a sexual partner or a household contact who has hep B, and we know that in New South Wales, there are some eligible groups who can receive this vaccination for free, through our general practice you can order this through WHO, and currently on the website they have that anyone who is Aboriginal, anyone with household and sexual contacts of acute or chronic hep B cases, anyone who is immunocompromised, anyone who has co-infection with HIV or hep C, MSM, anyone who does sex work, anyone who injects drugs, and anyone who goes to a sexual health clinic at their discretion. It is not everyone who turns up at a sexual health clinic, but sexual health clinics have their own set of rules about who would be eligible, and this slide shows us the geographic pattern of prevalence worldwide, and as you can see, most of that comes from the Western Pacific region, that is Asia, and particularly, Southeast Asia but also some Pacific Island nations as well and also Africa, that is 7.1% versus 6.5%, and in 2019, there has been an estimated 316 million people living with chronic hep B infection. it is quite a significant number. It is also important to remember, I guess, that lots of our patients are migrants from these high prevalence countries. When we are approaching these consultations, we need to exercise cultural awareness and think about the use of interpreters. This is a really great tool from ASHM. It is the decision making tool in hep B, and if you have not come across it already, it is amazing. It is something I use all the time as an S-100 prescriber, but anyone who walks in during a consultation who you are thinking, would they be at risk of hep B and wanting to look at whether this person would be suitable for testing or should I opportunistically think about testing all the way through to ordering the test, interpreting the serology and what to do in someone who is positive for hep B, what are the further investigations, what are the management steps, what are the monitoring steps and when should I refer. It is quite a handy tool to have and I think probably the only thing to take away from today's talk is that this is a really great resource to think of using efficiently during a consultation. I am just going to ask Simone now actually, Simone, do you use this tool as a specialist and how would you use it?
Associate Professor Simone Strasser
I can work out my camera. Thanks, Caran. I actually do. I keep it on my desktop, so I actually have it there, and every single new patient I have got with hepatitis B, I open it and I show them what the natural history looks like for them and where I think they sit in it, and patients get this and we talk a little bit more about the phases, but they understand what we are looking at, what the goals are, and why we are thinking about treatment, which again we will talk about a bit later while we do that, but I use it every day, every new patient I go through it with them not just for my reference, I do it with the patient.
Dr Caran Cheung
I have to agree. I usually pull it up as a PDF file from Google, and it conceptualises all of those things for them as well.
Move on to the next slide there. This is an enlarged graphic of the first page of this tool. It is a two-page tool. When ASHM was running face to face courses, they used to give these as a laminated handout. I guess you could also print it out and laminate it in your practice, but we might go through each of these segments in detail. For example, on the next slide, we have got here about ordering tests. Who do we identify as priority populations as far as that goes, who should we opportunistically think about testing for hep B? In the first section of the tool that talks about at the bottom there on the left hand corner, first of all to review informed consent before offering testing. To consider pre-test counselling, and think about things like cultural awareness and discussing the use of a professional interpreter at that stage as well, and these priority populations include anyone who is born in those intermediate or high prevalence countries that we showed that global prevalence chart from a couple of slides ago, and anyone who is identifying as Aboriginal and Torres Strait Islander, anyone who is about to undergo chemotherapy or immunosuppression due to the risk of reactivation if they have had previous hep B. We would like to find out even if it is resolved infection whether they have previously had hep B and we will talk about the serology what we are looking for that as well. Anyone who is pregnant as we know it is part of our antenatal serology testing, and so it comes in very handy at that pre-pregnancy or preconception counselling step as well as after they have come in and told you they have just conceived and that has some important implications, and tonight we are very lucky that Simone ha got a case on that and infants and children born to mothers who have hep B, so typically we do not test these children until 9 to 12 months of age because it does take around at least three months post vaccination for us to accurately measure whether they have got immunity and any people with clinical presentation of liver disease, so if they have physical signs or symptoms, overt signs or symptoms of chronic liver disease, we should think about testing and/or if they have got any abnormalities in their ALT levels on their liver function testing or an AFP of unknown origin. I guess you probably will not think of testing for Alpha-fetoprotein unless there was a clinical suspicion to begin with, but if it was positive and you have not done the hep B serology, then it is a good time to do it, and any health professionals who perform these exposure prone procedures, that tends to be us as GP's because we do a lot of suturing and skin biopsies.
Associate Professor Simone Strasser
We should all be vaccinated already. All medical students, nursing students and healthcare professionals should know their hep B status because they should have been vaccinated or if they have got chronic hepatitis B know their status. So, it is in there, but with hope in the current environment that everybody who is working in healthcare is vaccinated.
Dr Caran Cheung
Would you recommend regular monitoring for ourselves, regular testing, and how often should we as healthcare professionals?
Associate Professor Simone Strasser
Not for Hep B, if you have been vaccinated, but you might want to if you are particularly doing exposure prone procedures, check your immunity, check your surface antibody titre. There is not a firm recommendation to give boosters, but personally if mine dropped below ten recently I have a booster because why not, but yeah, it is monitoring of surface antibody in that situation. You are not monitoring for surface antigen because you are not likely to get hepatitis B.
Dr Caran Cheung
And any partner, household contact, sexual contacts of anyone with acute or chronic hep B, anyone who is ever injected drugs, MSM, anyone with multiple sexual partners, anyone who has ever been to jail, anyone with co-infection with HIV or hepatitis C, anyone undergoing dialysis, that is an important one to think about because there is this phenomenon, I believe, Simone, where sometimes the haemodialysis equipment does not quite filter out those hep B particles or molecules, and have you seen any instances in your practice where people have acquired hep B infection from dialysis?
Associate Professor Simone Strasser
Not in the Australian context that I am aware of, but incredibly common in Asia where they actually have major funding issues and they will reuse the tubing for a long time and I have visited hospitals in Vietnam where they have to reuse the tubing because they just cannot afford new tubing and they try and keep the hep B tubing separate from the other tubing, but of course that is not failsafe and the machines get an infection, so there is a lot of transmission, but again, really for all of those, except for the first one who have probably come to Australia already with hepatitis B, there is an opportunity to have vaccinated before beforehand. I think what the important message is if people are at risk, make sure we know their status, particularly that top group. If somebody has come from Vietnam, China, Hong Kong, wherever, they should know their status and you should know their status recorded once. You just have to screen them once. If they are not got hepatitis B, you might offer vaccination. If they have got all negative markers, but otherwise you need to know their status, and one other comment I was going to make is that there is a major study being led by Professor Miriam Levy from Liverpool, where we are working with her and we have implemented universal screening in emergency departments in Liverpool Hospital, Canterbury Hospital, I think Bankstown Hospital and several other hospitals where every patient coming through the ED is being screened for hepatitis B and hepatitis C. Actually doing consent in that situation they have given some information that they are going to be tested, but it is a part of if they are having a blood test they are getting tested as well, and then the GP will be contacted if those tests are positive. We are really ramping this up because there are so many people, particularly in that top group, people have come here from overseas who have never been tested for hepatitis B, and then what I see as a liver specialist is they turn up with a big liver cancer and that was preventable.
Dr Caran Cheung
That is a good point, and there is also, as we mentioned before, sex workers and anyone who we are thinking about initiating Prep for HIV prophylaxis and that is part of the baseline testing, if we look in the ASHM prep tool which is a separate tool on its own, which is also very good, but additionally to that, as Simone was saying, we should be offering testing to anyone who requests testing.
When it comes to ordering serology, that is the second part of the tool. We want to order all three of these tests in order to determine someone's status. If we order only hep B serology, if I write that on a form and it goes to Laverty or Douglas Hanley, more typically it does not come back with all three. In my experience from sending to Laverty, it comes back with hep B surface antigen only. In order to work out someone's status, it is important to order all three which is the hep B surface antigen, hep B core antibody and hep B surface antibody, and we will talk about that in the next section on interpreting serology. This is all covered by Medicare, and all we have to write is something along the lines of ? chronic hep B or ? hep B infection or typically I write that they are also sexually active or something. It does not fall foul of the Medicare rules. All three tests are repeatable and there is no limit on how many times a year you can order that under Medicare. In terms of interpreting the serology, this is where things get a little bit tricky sometimes, but actually it is quite simple when we refer back to the chart. Possibly only the last scenario is a bit tricky, and I will ask Simon about that, but the first situation you have is the surface antigen core antibody, surface antibody are all negative. That means that this person is susceptible to infection. They have not got immunity. The next situation you have got surface antigen is negative. They do not have current infection. Their core antibody is positive and their surface antibody is positive. It means that they have had previous or resolved hep B infection, and they have immunity through past infection. Would you say that is the case. They people would be immune if they were re-exposed to the virus.
Associate Professor Simone Strasser
They have had had prior infection.
Dr Caran Cheung
The next scenario surface antigen negative, core antibodies negative, but only their surface antibody is positive. This is the typical situation where you have got immunity through previous vaccination. So that is ideal. The next situation, surface antigen is now positive and typically what happens then is that the lab when I sent a lab video they will automatically then perform this core antibody if you forgot to order all three tests. Then if that core antibody comes back positive, then the lab usually runs this IgM as well, and if that is also positive, then that is suggestive of an acute infection, and Simone, the definition of an acute hep B infection is that within six months?
Associate Professor Simone Strasser
Yeah, but the clinical presentation is really somebody who comes in with very high transaminases. So AST and ALT, they might have had an exposure and as part of the WorkCover why this person has got an acute hepatitis based on their biochemistry, you do a hepatitis B core IgM and that will be positive and it will be particularly in a high titre. When we are screening for hepatitis B, just because someone is at risk from where they were born or during antenatal screening and they do not have illness, they do not have very high liver enzymes, then it is not going to be acute hepatitis B when we find it. We are particularly looking for a cause for acute hepatitis and we have to do that. The part of the case definition is you have got to have that IgM, anti-hb core, not just an anti-hb core.
Dr Caran Cheung
And the next scenario, you have the surface antigen is positive. They have got infection. They core antibody is also positive and the surface antibody is negative. In that situation, I am guessing that is an IgG that core antibody, from the lab perspective I mean they do not really list out this is an IgG, but yes, well in that situation, it is chronic as well because as Simone says it is not the IgM that is positive, and then the last scenario is a little bit tricky. It is when the surface antigen is negative, but you have a positive core antibody but a negative surface antibody. This scenario, we typically call it occult infection. Simone what sort of constitutes this occult infection and what sort of clinical scenarios?
Associate Professor Simone Strasser
Some people have hepatitis B where the surface antigen does not actually pick up in the assays that we use. They have actually got a mutant, it is not always in this scenario, but it is not uncommon when you test an HBV DNA in that situation, you might find it is positive. The person's got hepatitis B and it can reactivate in certain situations, but you cannot detect the surface antigen, and that is probably because they have got this escape mutant. It just does not pick up in the assay. It is real. I have seen that scenario when somebody who has had chemotherapy and they developed a severe hepatitis biochemically and they never became surface antigen positive, but they had a very high hepatitis B viral DNA. It happens if you see just an isolated core then they probably do not in a normal situation have a very high level of DNA, but they probably do have some hepatitis B around and it can reactivate. It is not a false positive anti-core in that situation it probably reflects infection but just a slightly mutated form of infection. It is not very common, but I am sure everybody has come across funny serology examples in their practice, and that is one of them.
Dr Caran Cheung
And in that scenario, is that HBV DNA level actually rebatable for GPs under Medicare?
Associate Professor Simone Strasser
Well that is a problem. You bring up a good point because at the moment HPV DNA is only rebatable if the patient has got hepatitis B surface antigen, and yet in my practice if I saw that serology I would order it. I would probably do it through the hospital where it is probably going to be done for free, but if you order it in the community, the patient will get a bill for the HPV DNA, which is like $80 or something. You have to warn them, but it is an important piece of information to know.
Dr Caran Cheung
It is not too expensive if we order it privately, but would you suggest in that scenario if, as a GP, we saw this serology, do you prefer if we refer that to a specialist setting?
Associate Professor Simone Strasser
No, you can just do a DNA. It does come back to why we do all three tests and particularly in the setting of when we are talking about patients having cancer chemotherapy or significant immunosuppression. If you do not do all three tests and you just, for instance, order a hepatitis B surface antigen or even a hepatitis B surface antigen and an antibody surface antibody, you will find they are both negative and you will miss the fact that that patient's actually got acquired hepatitis B, and when you stick them on a whole lot of chemotherapy, they can reactivate. That is why we recommend in those settings when we are doing testing we do all three tests because otherwise you miss stuff.
Dr Caran Cheung
Thanks for explaining that. That is really clear. Thanks, Jovi. This next section number four is on the initial assessment. If someone is surface antigen positive. We should carry out some baseline screening and the next slide we have is going to go through this phases of infection as well, but if we just go back to the slide before Jovi just here, the E-antigen status is really important in determining the phase of infection. We should order an E-antigen and an E-antibody, and as Simone was saying HPV DNA level, that is a quantitative level, and then we are thinking about liver synthetic function. We should organise them to have a full blood count liver function INR and then a liver ultrasound, and alpha fetoprotein can help us exclude a HCC or hepatocellular carcinoma, and sometimes a liver ultrasound is also useful because it can look for other comorbidities such as NAFLD or fatty liver disease or something else going on structurally, but it is very important here as well to think about a fibrosis assessment for every patient at baseline screening so that fibrosis assessment can include an APRI score or FIB-5 score or FibroScan. There is also places that do shear wave elastography if you do not have access to a FibroScan. Unfortunately, FibroScan are not repeatable by Medicare and only some places are offering these. I believe most sort of public hospital departments are offering FibroScan, especially yours at RPA, Simone, what is the wait if we were to refer a patient for a FibroScan to a tertiary centre?
Associate Professor Simone Strasser
It depends a bit where you are working. We have got a technician that just does FibroScan and we have got a referral pathway that is on health pathways. Most health districts will have some referral pathway, and I would suggest that people refer to their local pathways through health pathways.
Dr Caran Cheung
Health pathways would be a really good source of referral information for FibroScans. Other places that do them as well. Some of your local sexual health clinics would also offer FibroScans without much wait. And in addition, it is very important to look for co-infection at this stage, so that is hep A, hep C status, hep D, so hepatitis delta virus is actually a variant of hep B where it carries a very poor prognosis and HIV and other comorbidities as well at the same time, so AOD use, any diabetes, fatty liver disease, and then it is also important to have that conversation about encouraging your patient to speak to the household contact sexual partners to get them screened and vaccinated if they are susceptible. Medicare does cover the HPV DNA testing once a year for patients not on treatment, not on antivirals and four times a year if they are on antiviral. Thanks, Jovi.
There is a really important section here on this decision making tool. In highlighted in red right bottom hand corner, it gives you pointers onto when we should definitely refer for specialist advice, and these include anyone we suspect as having acute hepatitis B infection because of the risk of a fulminant liver failure Simone?
Associate Professor Simone Strasser
Yeah. Absolutely.
Dr Caran Cheung
There is also a co-infection because in co-infection the management is more complex. Anything co-infection with HIV, hepatitis C or hepatitis Delta virus, anyone who is pregnant, anyone who is immunosuppressed and anyone who has been previously treated with a HBV medication, and Simone, is that point about the possible resistance with that?
Associate Professor Simone Strasser
Some of the medications that we used to use in the past, particularly one called lamivudine and there were a few others, but lamivudine was the first hepatitis B oral drug that we had, and so there were a lot of people treated back in the day. The rates of resistance to that were very, very high, like 70% by five years on treatment. There should be really nobody left on lamivudine these days, and all patients currently, if they are on treatment, should be on either entecavir or tenofovir, which are associated with pretty close to zero resistance highly effective, and there should not be chopping and changing. If they are well suppressed on one medication, then I would not be chopping changing. I would not be giving them drug holidays. I counsel them about stopping treatment restarting because that is the time when you may get resistance emerging when you are on off, on off because that puts selection pressure on the virus.
Dr Caran Cheung
Refer if you feel that you are suspecting a HCC or any sort of liver lesion is present and definitely refer if cirrhosis is present.
Next slide please, Jovi. In terms of the phases of infection, this is the second page of the decision making tool. We are just going to click through to the next slide, which is on the assessing the phase of infection. There are four phases. The terminology had changed two years ago in 2022, and some of you may know it by the old terminology, but by the way patients can move through the phases. It is a dynamic process that does not have to follow a sequence. The first phase we are going to talk about is immune tolerance or otherwise now known as E-antigen positive chronic infection. In this phase, as you can see, the HPV DNA level is high but the ALT is low. For ALT, it is important also to remember that for women, ALT normal is under 19, but for men it is under 30 whereas when you look at the laboratory reference values that are given to you from say Laverty or Douglas Hanly Moir, it does say 30, but we need to remember that women it is actually under 19 and it says that on this ASHM tool. Treatment is not required in this phase because as you can see that ALT is not high, so the amount of liver damage is not going to be as high, and then the other next phase is the E-antigen positive chronic hepatitis. That was previously known as immune clearance. As you can see here, ALT is high, so there is flares for the ALT, and that is putting the patient at risk of liver damage, and that increases the risk of cirrhosis and the development of hepatocellular carcinoma. In the next phase they have there, so the next two phases will be E-antigen negative or E-antibody positive. E-antigen negative chronic infection was previously known as immune control. Patients can remain in this phase for many years sometimes decades, and treatment is not required in this phase as you can see because the ALT is low, and then the next phase which we used to call immune escape that is E-antigen negative chronic hepatitis. As you can see there is flares in the ALT, but the difference here is in the last two phases the HBV DNA levels are lower as well. It is under 2000 typically, but because of the ALT being high, there is a risk of liver injury, and so there is an increased risk of cirrhosis and HCC. In this phase also, we will consider patients for treatment. Anything to add to that, Simone for now?
Associate Professor Simone Strasser
No, I think I will discuss it when we get to the cases.
Dr Caran Cheung
In terms of ongoing monitoring, there is a really nice concise table here, and monitoring varies if someone is on treatment or not on antiviral treatment. An example here is if they are off treatment then you would consider looking at the LFTs every six months, and looking at the E-antigen E-antibody status maybe every 12 months or 6 to 12 months and having a look once a year at the HBV DNA level and then also doing a fibrosis assessment, whereas if they are on treatment then the monitoring is a little bit more involved. It could be, four times a year, for example, for the first year, but the main important takeaway is that not everyone with hep B or chronic hep B will require treatment, and treatment is dependent on the phase of infection and also if they have any other comorbidities such as cirrhosis or pregnancy or immunosuppression, and it is important to when it comes to thinking about treatment or thinking about monitoring that, you maybe wanting a little bit more advice on to refer to an S-100 community prescriber or to a specialist, but definitely for most of us, for all GP's we should be able to monitor a patient who is not on treatment maybe with some advice from the specialist or in collaboration in a shared decision making way, but all of us are able to do that monitoring even if we are not S-100 prescriber.
Associate Professor Simone Strasser
Caran, can I just make a point about HPV DNA testing and someone who is not on treatment? If there are only funds once a year and it is set in the computer to once a year as in 365 days, so if you ordered 364 days after their last test, they will get a bill for it. If you order it 366 days after their last test, they will not get a bill for it. It will be bulk billed or whatever, so just remember that if you are doing an annual monitoring and I think everybody with who is hepatitis B surface antigen positive should have annual monitoring of their DNA because it does change. Make sure you do it one year and one day and not sooner.
Dr Caran Cheung
Thanks for that practice. I guess the most important takeaway from this slide is that monitoring is really, really crucial to limiting people progressing to cirrhosis and developing HCCs. That is where we play a part, and thanks, Jovi. The other critical area on this handout is that about HCC surveillance. These are the risk factors or priority groups where we consider for HCC surveillance on a yearly basis at least or every six months depending. That is a liver ultrasound plus or minus alpha fetoprotein and Simone alpha fetoprotein, it has become a little bit controversial, but I understand in your practice, you still order it elaborate briefly about this?
Associate Professor Simone Strasser
In hepatitis B and now in treated hepatitis C, I actually always order it, and you do see some patients where the liver ultrasound is not showing any lesion, but you are seeing a progressive rise in the AFP and it just pops over normal, and invariably in those patients, you will find a cancer at some point. It might be an early marker and the combination is more sensitive than one alone. Having said that, the sensitivity of even a liver ultrasound and an AFP is still only around 63%. You are still going to miss cancers with that strategy, but unfortunately, it is the most cost effective strategy that we have now. In the future, we may have other biomarkers, we might have better imaging, we might do other things, but at the moment, the most of cost effective strategy from a population point of view is a six monthly liver ultrasound with or without, they say AFP. That is mainly driven by the Americans I think. I would do the AFP as part of that surveillance because you do pick up a few more.
Dr Caran Cheung
The AFP is rebatable by Medicare as well.
Associate Professor Simone Strasser
Yeah and the ultrasound is.
Dr Caran Cheung
Anyone with a history of cirrhosis, anyone who is 40 years or over with any family history of HCC in a first degree relative, but you would also consider offering the surveillance process earlier, so ten years before the last person in the family developed HCC, so very similar in that vein to colorectal cancer screening, and anyone who is from sub-Saharan Africa who is 20 years and over, anyone who is Aboriginal and Torres Strait Islander, who is 50 years and over, and any Aboriginal and Torres Strait Islander with high risk features 40 years and over. What are some of these high risk features Simone?
Associate Professor Simone Strasser
It is particularly if they have got liver comorbidities, so fatty liver disease is really common due to diabetes obesity and due to alcohol, and we know in particularly in metabolic associated fatty liver disease as it is called now that a significant proportion of people are developing cancer in a non-cirrhotic situation. We do not necessarily screen them, but if I see somebody who has got chronic hepatitis B, they are indigenous, they have got these other comorbidities, I might start them a bit earlier or they have got a family history of HCC, we might start them a bit earlier. I mean these are just that guidance, we will see cancers arise in people outside of those categories, but again, from a population level surveillance strategy, this is what has been set based on the current data.
Dr Caran Cheung
And that includes also Asian Pacific men over the age of 40 and Asian Pacific females over the age of 50. Anyone who is Asian and from Pacific Islander nations. Thanks for that, Jovi. Now we will hand over to Simone to go through some case studies and feel free to pop your questions in the chat, and I will be monitoring the chat and interrupting Simone to ask those questions.
Associate Professor Simone Strasser
I have answered a few of them just typed if anyone wants to follow up, but I thought they were fairly clear and I have answered them. We will go through a couple of cases that that you could easily see in your practice tomorrow. The first one is a 67-year-old woman. She has moved from Hong Kong to Australia about 18 months ago, and she is now living in Sydney with her husband. She is actually known to have hepatitis B for many years. She was diagnosed during antenatal testing 40 years ago when she was 27 in Hong Kong, and most recently she has been undergoing monitoring with her liver team in Hong Kong with annual blood tests and an annual ultrasound examination. They do that for cost effectiveness in a Hong Kong situation where these tests are more expensive. That is not what we would recommend for screening and surveillance. We would recommend six-monthly blood tests and particularly the AFP and six-monthly ultrasound exam. It is not what we do in Australia and we would change that. Her last ultrasound was 12 months ago. She has never been treated with antiviral medication. Her family history is significant. Her brother has hepatitis B and a history of liver cancer, and he underwent a resection for that. Her sister also has chronic hepatitis B and not surprisingly, her son who was born when she was 27 also has chronic hepatitis B and he is not under regular monitoring. She has been overweight in the past, but she has got no other significant health issues, no regular medications, and she is a non-smoker and non-drinker. Thanks, Jovi. Here are her blood tests. ALT is 49 and AST 42. Already I am going "They are high because Caran just told us that in a woman, a normal ALT should be 19 or lower. That is based on studies showing that all-cause mortality increases from that point due to liver injury. The most common cause of when we see that is obviously in fatty liver disease, but her ALT is quite high. It is two-and-a half times that. Having said that, her bilirubin is normal, her albumin level is normal and very importantly her platelet count is normal. AFP level is low at two. When we do a hepatitis B testing because we know she has got hepatitis B and we would have done it anyway because she is an Asian woman from Hong Kong who is at risk, we find she is surface antigen positive still. She is E antigen negative. She is anti-HBe positive and she has got a viral load that is reasonably high. It is over a million, very high. It is particularly an E antigen negative disease. She has never been on antiviral treatment if you remember.
I do a FibroScan as part of my physical exam because I can. We can also run tests such as an APRI score or a FIB-4 score to assess the likelihood of fibrosis, and hers would likely be a little bit high because the AST and the ALT are quite high, although her platelet count was normal. If we do a FibroScan, we get two bits of information. The FibroScan image that we see on the screen and you can actually see me in the image there because that is one of mine, you can see that the median liver stiffness, which is that orange number is 8.4 kilopascals and that is a little high, that is probably in the range of having moderate fibrosis, but not cirrhosis. We start talking about cirrhosis when that reading is over about 12.5 or 13. It is probably moderate fibrosis. It is not negligible. The other reading we get on a FibroScan is the blue number, and that is the CAP score, which tells us about the fat content of the liver. We get that routinely on the modern FibroScans as well, and incredibly useful information when we are assessing people, for instance, for fatty liver disease or for other liver diseases. A normal value would be under about 220 for that. I have got two bits of information from this FibroScan. One is that she has probably got moderate fibrosis, and the other is that she has probably got some fat in the liver. She has probably also got an element of metabolic associated fatty liver disease. Remember she was overweight as well. That is another target for treatment because we are going to focus on her losing a little bit of weight, eating a little bit more healthily, maybe exercising a little bit more. We are worried about a hepatitis B that is a separate target for treatment because she has got moderate fibrosis and she has got a high viral load and her ALT was high, all of which are indications for treatment.
Next one, Jovi. What phase of hepatitis B is she in? There are a number of questions and we might just load all those questions up and I will come back and answer them. Thanks, Jovi. The first one is what phase is she in. Well she is E antigen negative but she has got a high HPV DNA and a high ALT level. That pushes her into that immune escape or E antigen negative chronic hepatitis phase. Phase 4 to the far right of that diagram. Remember, that was an indication for antiviral treatment if you are in phase 4 to reduce the risk of progressive liver injury and liver cancer. Is antiviral therapy indicated? I think I just answered that. Yes, absolutely indicated in someone like her. She may not be wanting to start treatment, she might want to negotiate. I have got people like this all the time. It takes me sometimes two or three visits to convince them that they need to be on treatment. They may not be all that accepting at the first visit, but I will be pushing pretty strongly. Why should she be treated? She has got a family history of HCC already. Remember, her brother had HCC and she has got moderate fibrosis and she has got active liver inflammation. They are all good reasons. We want to prevent her getting cirrhosis and liver cancer. Remember again that hepatitis B liver cancer can occur in the absence of cirrhosis. That is why we have got screening based on age, not based on cirrhosis status in hepatitis B. Is HCC surveillance indicated? Yes for two reasons. One is her brother had HCC, so she has got a family history. Secondly, she is older. She is over the age of 50 and that alone would be enough in our current guidelines in somebody who is hepatitis B surface antigen positive regardless of whether they are on treatment, got inactive disease etc. Yes, it is indicated. How should it be performed? Six monthly ultrasound and AFP is really what is recommended in somebody with hepatitis B. Remember if somebody has got active hepatitis B and their ALT level is a bit high, the AFP level can be high as well. When you treat them and their ALT normalises, the AFP should settle in that situation in the absence of HCC. It is a little bit of why that plus and minus AFP is because you can get false positive elevations of AFP, particularly in people with active hepatitis. Would you consider screening her husband for HPV infection? I assume he is also from Hong Kong. If he has not been screened, which I hope he has, yes, he should be screened with a surface antigen, core antibody and surface antibody. To determine his status, if miraculously he has got to age of 70 or so and has not had exposure to hepatitis B before, he should be vaccinated and he should be just determined where he is at. He may be in that immune control phase or that E antigen negative chronic infection phase. Would you recommend her son to be monitored? Yes. Men with hepatitis B are more likely to get HCC actually. He needs to be fully assessed on his own. His current status, his liver enzymes, his FibroScan, his E antigen status and his viral load, etc. An independent determination for treatment needs to be made. Also, he is now 40, so he needs to be started on HCC surveillance as well.
Dr Caran Cheung
On that note, we have got two questions from the audience. For HCC, if you are suspecting it, and if the ultrasound and the AFP are normal and you still suspect it, then what is the next imaging we should order? Is it some sort of a CT or MRI?
Associate Professor Simone Strasser
I am not sure why you would be suspecting it. If somebody is losing weight and they have got pain and something clinical, what we are trying to find is really preclinical HCC. If the ultrasound is a good ultrasound, they have seen all parts of the liver. The person is not obese. We can be pretty confident they have seen all of it. Sometimes now they report a visualisation score. If it is A or B then you can be pretty confident they have seen most of the liver. If that shows no lesions at all and the AFP is completely normal, then I would not be doing another test necessarily because what we are trying to find is small cancers. If someone has got pain, weight loss, you are investigating them for another reason, but for a surveillance situation, what do you do if you find a nodule? If you find a new 1 cm nodule, 1.5 cm nodule, which is what we are looking for in screening or we have got a negative ultrasound, but the AFP level is rising, the next test that is funded is a CT scan, and it must be done as a four-phase CT scan. That means non-contrast arterial phase, portal phase and delayed phase. You have got to specifically request four-phase CT because you will miss HCC on just a post-contrast CT scan. It must be a four-phase CT. You can also use a multi-phase MRI scan, but they are not funded unless you have found a lesion already on the CT that you need to characterise further and then it has got to be ordered by me anyway. That is just a four-phase CT, and then you have got that information and you can make the referral through to our HCC MDT that we run every week.
Dr Caran Cheung
That answers the question. Thanks, Simone. I have also got another one coming in. If someone has a history of past infection, can they receive hepatitis vaccine?
Associate Professor Simone Strasser
If you mean that are they anti-HB core for and anti-HBS positive, they do not need a vaccine or if they have got surface antigen. If they have had hepatitis B in the past, have hepatitis B currently, there is no indication for a vaccine. The only time you are going to be vaccinating someone who is negative on all three tests.
Dr Caran Cheung
Thanks, Simone.
Associate Professor Simone Strasser
Okay, Jovi, we will move on to the next one. She was someone you might see quite often, but you can see how many things we have got to be thinking about. We are thinking about her MAFLD, fatty liver disease. We are thinking about her hepatitis B, the treatment. If we are going to treat someone like that, I would be treating with entecavir probably rather than tenofovir. She is an older woman. Tenofovir is associated with perhaps some bone damage. Osteopenia or osteoporosis and also some renal impairment. In older people, I worry about that. I would use entecavir 0.5 mg once a day in somebody like that when I am going to treat and it is very cheap these days and it is on the PBS.
Case number 2. Again, if you are doing shared care or seeing women that turn up pregnant, you are going to be doing antenatal screening. This is a 29-year-old woman. She was born in Vietnam, moved to Australia when she was 12. She is currently 12 weeks pregnant with her first child, and she comes in for routine antenatal screening, albeit a little bit late. Her parents and brother live in metropolitan Sydney as well. Her past history, she is on no regular medications, no other past history. Here are her blood tests. She is surface antigen positive on an antenatal screen, but hepatitis C negative and HIV negative, also part of your antenatal screen. You have probably seen people who turn up like that.
Next slide. Her blood tests. Does she have hepatitis B? Yes, she has got hepatitis B because she is hepatitis B surface antigen positive. If you are wondering does she have acute or chronic. Again, it is that point I made earlier. You are doing this in the context of screening because she is pregnant, not because you are doing a test because she has come in with acute hepatitis and has transaminases of 800, 1000 or something. She hs come from Vietnam and she was probably born before there was routine vaccination in Vietnam. If you find hepatitis B, you do not have to even raise the question of whether this is acute. You do not need to do an IGM in this situation. What I have seen, you also do not have to sort of start asking a lot of questions because the patients and their families sometimes in this scenario when they are found to have hepatitis B or sometimes there are questions about "Oh, maybe she used drugs, maybe she is a prostitute". All these sort of questions that you need to turn down really, really early and discuss. This is really common in Vietnam. It is very likely you got this on birth and the most likely risk is that your mother also has hepatitis B, which comes to the rest of her family. What do you want to know about her hepatitis B status? We need to do the full gamut of the tests to work out her current status. We want to know her E antigen, E antibody, HBV, DNA and her liver enzymes. Then what are the implications of being surface antigen positive in pregnancy, we will explore on the next slide.
Here is that extra information that we wanted. She is hep B E antigen positive, E antibody negative and she has got a very high viral load, 8 log10 is 100 million. Her alt is normal. She is in that first phase. She is in what we used to call immunotolerant phase or E antigen positive chronic infection. It is associated with very high HPV DNA, but no evidence of liver injury. She is not at risk herself at the moment. She is perfectly healthy, but she is walking around with very high level of hepatitis B DNA in the blood, and that is what many people have vertically acquired hepatitis B in their first two to maybe three decades of life will look like be in that phase. A lot of pregnant women who are found to be hepatitis B positive, particularly younger ones, will be in this phase of infection. We will go into the next slide.
A situation like that, which has got very high viral load, all babies in Australia are going to be vaccinated and have hepatitis B immunoglobulin and vaccination. All babies will get it within the first day of birth and then a routine vaccination schedule. In babies born to women who are hep B positive, their babies are going to get a hepatitis B vaccination and hepatitis B immunoglobulin within 12 hours of birth, hopefully within four hours of birth. However, in the situation like this, where she has got a very high level of viral load, that strategy will fail in up to 10% of women and their baby will get hepatitis B, so the World Health Organisation, Australian guidelines, international guidelines all recommend that we use an antiviral therapy, particularly tenofovir, in the third trimester from as early as 28 weeks and I usually start them at 28 weeks with tenofovir one tablet once a day. That will reduce the risk to the baby to almost zero. They still need to get their hepatitis B immunoglobulin and vaccination at birth. Having the mother on antiviral therapy up to the time they deliver from about week 28 to 30 will reduce that risk significantly, and it is recommended in all guidelines and it is funded on the PBS to do so. So very, very strong indication. I usually test women who are hepatitis B surface antigen positive at around week 20 of pregnancy to see what their hepatitis B DNA is at that time, and then discuss with them that they are going to start on treatment when they get to about week 28, week 30. Regardless of viral load, as I said or babies born to women who are surface antigen positive, will receive hep B immunoglobulin vaccination and they should have follow up serology. So the guidelines suggest that the baby be tested for hepatitis B surface antigen surface antibody from about nine months of age, three months after their last vaccination, and that is particularly important in babies born to women who are E-antigen positive just to make sure they have not got hepatitis B and they do have good antibodies from their vaccination. In this situation, women who are high viral load will should be referred to as S100 community prescriber or a specialist to have that discussion about antiviral therapy. I usually continue it until 12 weeks postpartum, so I give them a six-month course and that is what is on the PBS. They have 12 weeks before 12 weeks after, and that is just because they will probably flare to some extent once they come off antiviral therapy, and you do not want that to happen just as they are really exhausted with a newborn baby, so I usually keep them on it, and then ASHM has got a referral information as well, and I think that is the end of the slides, and just some clinical resources and other resources are shown there and you will be given those information.
Dr Caran Cheung
There are lots of good resources there, and I think the ASHM's new resources B-referred that got released last year. That is the B-referred hepatitis B for primary care. If you click on that, there is also a tool, like an interactive tool that you can step by step enter the data and see whether or not, what is the next step in case you wanted to not use the decision making tool that we talked about, but to have something interactive to put your patient information through. We have also got some questions. So, there is one question here asking apart from humans, is there another reservoir for hep B virus? And if not, does it mean that we can eradicate hep B through vaccination?
Associate Professor Simone Strasser
The hepatitis B that infects humans is unique to humans. There is other it is probably in primates, but I do not think that is a major risk. There are very similar viruses in ducks and in chimpanzees and in other species that have been used for study, but yes, I mean, the WHO has set a global elimination target to get rid of hepatitis B, and we are going to do that through vaccination. That is different from hepatitis C where we are going to do that through treatment and through harm minimisation, but for hepatitis B, we are really going to do that probably by vaccination and treatment of the patients who are already have hepatitis B. You would hope in 60 years' time, we are not going to be seeing hepatitis B anymore, and almost all countries have got hepatitis B vaccination schedules, but in many countries where babies are born in villages and out of mainstream care, there are people that escape, and get through childbirth without getting vaccinated, unfortunately, will still get hepatitis B for some time.
Dr Caran Cheung
Thanks, and we have got a few questions on the last case there. I do not know how many things will go through, but, one question is if she was not pregnant, will we still be treating her or would we be observing?
Associate Professor Simone Strasser
We generally tend to observe the current guidelines in Australia are that we only treat when there is liver injury, either on a FibroScan or liver test, and in that first phase immunotolerance, we tend not to treat. There is not good evidence that treatment changes the outcome. Having said that, China has just introduced a national policy where everybody with viremia is treated and the WHO supports that approach. That may change in the future, but current Australian guidelines would have her monitored and at some point she will probably go through an E-antigen seroconversion and during that time become active, and that might be a time to treat her, but I would not treat her right now. Is there a risk of antiviral use during pregnancy? Well, we used xenophobia because it is got the best safety data because it is a standard use in HIV prophylaxis of a HIV positive mums having with babies, and so we have got a huge amount of data on the safety of tenofovir and we are very comfortable with its safety, and that is why the WHO and the Australian guidelines recommend tenofovir. We have got no data for entecavir. If somebody young women who I am going to start an antiviral treatment who might have a baby, I tend to start on tenofovir. If they start on entecavir then I switch them if they are planning pregnancy or they come to me pregnant, and then in pregnant women with a chronic hepatitis B with a low viral load, so less than 200,000 IU/mL, they do not need their tenofovir introduced at week 28-30. Their baby just gets HPV and vaccination from birth and then gets a check-up because their risk is very, very low of transmission.
Jovi Stuart
Thanks, Caran and Simone. That is all that we have got time for this evening. Thank you everyone who has joined us online tonight. We hope you have enjoyed the presentation, and if you have missed any part of tonight's webinar, a recording will be available on demand page on the RACGP website within the next week. I will try to get it out by Friday this week. And lastly, just a reminder that as this is a CPD accredited activity and if you are an RACGP member, to be allocated your CPD hour, you must complete the survey following this webinar. Thank you everyone and good night.