Speaker 1: Hi everybody and welcome to RACGP National Webinar Series. I am Dr Natalia Rode your webinar facilitator this evening. I would like to start by acknowledging the traditional owners of the land on which this meeting is being accessed today and pay respects to elders past, present and emerging. Before starting, I would like to run through some features to make sure you can interact throughout the webinar. The first bit is about the control panel and you shall be able to see the slide, let me know if there are any issues with seeing that and you should be able to see the control panel, like the image on the right of your screen. If you can only see a few icons like the image on your left, please click on the red arrow to open up the rest of the control panel. The control panel provides you with the tools to select your audio options and it is also the place to ask questions during the webinar. You can send questions throughout the webinar and we will have half an hour of question and answer at the end. We may be able to clarify certain points during the presentation if needed. We may not have time to get into all questions, but we will endeavour to answer as many as possible.
To test this feature please click where it says enter a question for staff and type in where you are located today and then press send. We are just waiting to hear from you. Can anybody else try typing into that question box? Got someone from Perth, excellent, welcome; a few from Sydney, Newcastle, Kerang, Warrigal, Gold Coast, great, Broken Hill, fantastic, we have got people from all over the place. Well, welcome everyone and I am glad that you can obviously hear me and have found where to type your questions, so that is great.
We are going to move on to the next bit which is just testing a poll slide, so during this webinar we are going to be using polling features, we are going to practice this now, so you should all now have a poll on your screen, which will be great if you can answer that, so you just select your response and press submit. Okay, great, so thank you all for answering, we can see that about 30% of you are currently treating patients with chronic hepatitis B and 70% of you are not, thank you. Now in terms of QI&CPD requirements, if you have entered your RACGP number when you registered for the webinar and you stay for the whole webinar and complete the survey at the end, you will receive 2 category 2 points. So, now that we know that you can all interact with us via the polls and the question section, we are going to get started. This webinar is partly supported by ASHM, which is Australasian Society for HIV, Viral Hepatis and Sexual Health Medicine. Tonight’s webinar is on hepatitis B - How many of the 85,000 people living with undiagnosed chronic hepatitis B are attending your practice. What we know is that 234,000 people are living with chronic hepatitis B in Australia but only 6 in 10 are diagnosed and 2 in 10 are engaged in care. Nicole is going to tell us a lot more about this and I would like to introduce her for tonight’s webinar. Nicole is a GP and hepatitis B section 100 prescriber, who has recently completed her PhD in the epidemiology of hepatitis B in Australia and the health system response. She works in the community health centre in West Melbourne and is a postdoctoral researcher of the World Health Organisation Collaborating Centre for viral hepatitis at the Doherty Institute, over to you Nicole.
Speaker 2: Thanks Natalia and welcome to everyone today and thank you for your interest in hepatitis B. First, I just would like to say I have got no conflicts of interest to declare and I would also like to acknowledge the traditional custodians of the land that we are on here and where else the webinar is being accessed.
Okay, so for tonight’s Webinar, we have got various learning objectives, so the idea is to have a clear idea of who are the priority populations for hepatitis B testing in Australia; correctly know which tests to order to diagnose hepatitis B; how to interpret serology and to understand the intervention points and the natural history of hepatitis B; and what is required in terms of both treatment and regular lifetime monitoring. Now, to present some of those learning objectives, we are going to have a case that we follow later in the webinar and there are also some slides on background on epidemiology, as well as some polls along the way that we are going to conduct.
So, this is just the overview of the presentation tonight and I will move on because I have really talked about that on the previous slide, so first we are just going to start with a polling question, so how many people worldwide are living with chronic hepatitis B, so the poll is now open and if you just want to put in your answer, so it is A 1 million, B 50 million, C 150 million, D 250 million. So, we are just waiting if everyone put their votes in, that would be great. We tend to close it off after a certain number of you have voted, so get your response in quickly. Okay, so we are going to close it off and we will have a look at the poll results. Okay, so, about 40% of you thought it was 150 million living with hepatitis B and 28% of you got the right answer, which is D, so for hepatitis B there is approximately 250 million people worldwide living with chronic hep B. Now, the majority of them are in the Asia-Pacific and that is obviously the size of populations in the Asia-Pacific, specifically China where there are over a billion people and you know very large over 100 million people living with hepatitis B and then in Africa, the Americas, Europe and the Middle East.
Hepatitis B is thought to be the second most important human carcinogen after tobacco, so hepatitis B itself the virus actually is the cause of cancer as well as if you have got a damaged liver that is also risk for cancer, and someone dies of hepatitis B every 44 seconds in the world and this is approximately 700,000 deaths per year. Again, the majority of those deaths are occurring in Asia and the Pacific where the larger population groups are.
So this is really just the same bit of information presented on a world map showing that half the people living with hepatitis B live in an area with intermediate or high prevalence and there are some definitions around what that means, high prevalence is when greater than 8% of the population have hepatitis B; intermediate is between 2 to 7.99999 and then low is less than 2%, so when we look at Australia, we are a low prevalence country so we have less than 2% living with hepatitis B. The arrows represent, we are a source migration country, so obviously we receive migrants from all over the world and that is specifically from Asia and Africa where they do tend to have high prevalence of hepatitis B.
So this our second polling question and the poll is already open, so if we think of Australia, how many new hepatitis B infections are notified each year, so I just want to clarify we are not referring to transmission in Australia, we are just referring to the fact how many people are notified so they could be people coming from overseas and being diagnosed for the first time in Australia. So how many new hepatitis B infections have notified in Australia each year, and then it is A 250-500, B 1000, C 3000-4000 and D 6000-7000. Please just note there is an error on D it is has got 70000 it has meant to be 6 to 7000 that is just an error. Okay we are about to close off the poll, now again, 1000 to 15000 was the most popular response 43% of you responded that way, the answer is actually D, which is 6000 to 7000 not 70000, so 1500 is probably actually about what we see Victoria alone, a bit more in NSW.
So in Australia 234,000 people estimating are living with hepatitis B that is 6000 to 7000 notified each year and that has been stable for over a decade, that number of notifications. Overall, the prevalence is 1% of the population and it is a 4% prevalence in Aboriginal and Torres Strait Islander People and at the moment, we have 343 general practitioners who are accredited to prescribe treatment.
So, if we come to Australia and we look at who is living with hepatitis B in Australia, again the majority were born in Asia, Southeast Asia and Northeast Asia but then other risk groups include people born in Europe especially around the Mediterranean, so post war migration from the Mediterranean countries in Europe people born Sub-Saharan Africa and then other regions covers the rest of the world, all indigenous people have a higher rate of hepatitis B, so if you are a Maori from New Zealand, most of the Pacific Islands, they all have much higher rates of hepatitis B. Our own indigenous people Aboriginal and Torres Strait Islander People also have a higher chance of having hepatitis B and they represent about 6.3% of the population living with hepatitis B. Other risk groups include people who have risks of blood borne viruses generally so that is men who have sex with men and people who inject drugs.
So, the key points of epidemiology are that hepatitis B is a worldwide issue. The majority of people who are living with chronic hepatitis B in Australia actually were born overseas and when they were born overseas, they acquired hepatitis B, usually at birth or in very early life and then migrated later to Australia and often are diagnosed as adults here. Aboriginal and Torres Strait Islander people are also a priority in terms of they have a higher prevalence of chronic hepatitis B and should be offered counselling and testing.
So, the next section of the presentation just covers why we are thinking about hepatitis B, what does it matter, what are the consequences of hepatitis B infection. So chronic hepatitis B is a cause of liver cancer and worldwide it is the most common cause of liver cancer, the risk of developing liver cancer is much higher in people living with hepatitis B and liver cancer is the fastest increasing cause of cancer death in Australia according to the cancer report and there has been a 200% increase in liver cancer between the 1980s to now.
Early detection of liver cancer is important, but I would probably say more important is actually prevention of liver cancer, so early detection is early diagnosis of people with viral hepatitis both B and C, but if we are thinking about C it also includes once diagnosed with hepatitis, having regular liver cancer surveillance, regular testing and monitoring and being appropriately put on antiviral treatment if someone needs it and we will cover off who is eligible for treatment later. So early detection is the key for liver cancer surveillance. There is no national screening program, so it is very much up to clinicians to initiate regular testing, which is six monthly ultrasound tests and an alpha-fetoprotein level and then the risk groups that we consider doing this for are any patients with cirrhosis from hepatitis B but that also is just a practice point, it should be cirrhosis from any cause, people with a family history and then it is according to age and risk group, so Asian males it is over 40, Asian females over 50, people from Africa, men and woman over 20 years of age because there is a higher incidents of cancers at a younger age associated with a subtype of hepatitis B, and in Aboriginal and Torres Strait Islander people greater than 50 years. The message in terms of surveillance is that if a liver cancer is detected, it needs urgent referral to a specialist centre, so it is a phone call.
Now we are going to talk about transmission and prevention of hepatitis B; so transmission of hepatitis B as I have discussed a little bit earlier, it is actually most common at the time of birth or in very early life, so both vertical or perinatal transmission and horizontal is the most common way hepatitis B is transmitted worldwide. It can be sexually acquired, it can be associated with blood and body products and blood transfusion or unsafe medical procedures, especially those performed overseas where there is poor infection control. If we look at people living in Australia the vast majority acquired the hepatitis B at the time of birth or in early life and we know that actually because children who get hepatitis B early in life are 90% likely to carry it as a chronic infection, whereas if an adult with a more mature immune systems is exposed to hepatitis B only 5% to 10% will get chronic hepatitis B. The majority will clear their infection.
Oh dear, I think I have just answered the next question unwittingly, but anyway you would just to have to say if you actually listened to the bit I obviously jumped ahead, so what is the likelihood of a child infected with hepatitis B going on to develop chronic infection and this is actually a newborn, this is not a child this is a newborn, what is the likelihood? So, you should all get this right because I gave away the answer.
Okay, so excellent, the answer is 95% so again that is a newborn baby with a less mature immune system actually allows the infection that goes into the liver cells and then it becomes a chronic infection.
Okay, so now if we are looking at transmission of hepatitis B and we look at the countries and where transmission is taking place, so transmission is taking place through early childhood contact and perinatally in the vast majority of the countries across the world that have hepatitis B, intermediate or high prevalence hepatitis B. In a low prevalence country, the risk is more in adults through sexual transmission; however, most of them will not progress to chronic infection so less than 5% progress to chronic infection. Australia is overall low prevalence, but certain groups have a high prevalence and they are people who were born overseas and Aboriginal and Torres Strait Islander people.
The risk of hepatitis B infection from exposure to body fluids; so, basically high risk is any blood serum wound exudate, semen and vaginal fluid and safe are urine, faeces, sweat, tears and breast milk. It is very important that breastfeeding is promoted in woman who have hepatitis B and there is no benefit to other forms of delivery like caesarean section either, so salivary transmission is very very rare, it does occur through human bite exposures when there is blood present and sharing food and drink is definitely not a risk. Transmission messages are very important when you talk to people with hepatitis B. They sometimes self-stigmatise and keep themselves away from family and friends, do not hug their grandchildren and so on because they are worried about transmitting the virus to their loved ones, so it is an important part of communicating a test result that we accurately communicate the transmission and also let them be aware that there is a very effective vaccination.
Currently in Australia we vaccinate all newborn babies so there is birth dose vaccine, which is less than 24 hours given universally to all babies born in Australia since 2000 and in the northern territory that started approximately 10 years earlier in 1989. There is also hepatitis B infant vaccination which is part of the normal infant schedule and then immunisation is provided free for certain groups by different state and territory governments and it can be ordered by GPs through your health department and there is a link on this slide to hepbhelp which has specific groups that are eligible for vaccine. If we are looking at, particularly I will talk about Victoria but it is very similar across many jurisdictions, you can give it to people who are sexual or close contact with household members someone with hepatitis B, also men who have sex with men, people living with HIV, people living with hepatitis C, people undergoing dialysis, and sex workers, and you can also give it to people from sort of high-risk cultural and linguistic diverse background in Victoria. So just check with your local jurisdiction with hepbhelp and be aware that that exists but when we are talking about people who need vaccination, they often need testing first. There are always questions when we do hepatitis B discussions about non-responders to vaccination, I would refer you to the Australian immunisation handbook, it has an excellent section on non-responders and the steps you should take.
Key points on transmission and prevention is that most people living with hepatitis B in Australia acquire their infection at birth or in early childhood, usually overseas in the country of birth. Most acute hepatitis B infections in Australia are due to sexual transmission or unsafe injecting drug use. People for certain groups can access free vaccination and GPs play a very critical role in prevention, vaccination and promoting harm minimisation strategies.
Next we are going to talk about testing and interpreting results.
Speaker 1: Oh good we have got a question about vaccination doses for poor responders, I do not know if you want to answer that question now or a bit later
Speaker 2: Yes look the best place to look for that… there are actually different techniques, revaccination, intradermal vaccination, you can double dose vaccinations, but there is a really good section in the immunisation handbook but also with non-responders, just always check that you have actually tested them for hepatitis B first as well.
Okay, so why is testing so important, this is the cascade of care for people living with hepatitis B and the top bar represents the 234,000 people living with hepatitis B, of who we think approximately only two thirds have been diagnosed, that is basically just over a third undiagnosed and in terms of who is receiving regular monitoring and assessment of their liver function, their viral load, ultrasounds if need be, it is only 20%, so it is only about a third of those people diagnosed are receiving some form of regular testing and we will get to the recommendations of what testing is later and at the moment we have got a little bit less than 20,000 people on treatment in Australia. Hepatitis B is a little bit complicated, not everyone needs treatment. If people’s immune system is controlling the virus and their liver is healthy, they do not need treatment and we estimate around 20% to 25% actually will need treatment throughout their life. So currently there are at least 30,000 who are not receiving treatment who should be.
These slides were put together by ASHM, I probably in retrospect would have changed this slide a bit. The clinical indictors for testing obviously if someone presents with abdominal pain, fever, joint pain, loss of appetite, weakness, fatigue, dark urine, yellowing of the skin, this is suggesting an acute hepatitis and you would include hepatitis B testing and you would also include A and C. Actually, for most people chronic hepatitis B is asymptomatic and so you are opportunistically testing people, particularly in these two risk groups.
People born in intermediate and high prevalence countries an Aboriginal and Torres Strait Islander people. In the national testing guidelines there are other groups as we mentioned before other priority populations who we would test including men who have sex with men, certainly anyone with an HIV diagnosis, anyone undergoing dialysis, but in terms of actually finding the undiagnosed, these are the two main populations. This is the list of the sort of extended group of people we should be considering testing in; so pregnant woman which is the only routine testing we do, unvaccinated adults with increased risks of infection, people living with hep C, clinical presentation of liver disease or elevated ALT, health professionals involved with exposure prone procedures and members of the armed forces.
To discuss testing and hepatis B, we are going to use a case study. So, Chen is a 28-year-old Chinese student who comes to your practice after a recent trip to China, where he attended the funeral of his father who died of a liver tumour. He is attending your practice as he had had an upper respiratory tract infection while overseas. Throughout this case study, we would like you to refer to the handout which Natalie is now going to tell where it is.
Speaker 1: So if you go to the control panel you should be able to see, there is a little dropdown arrow that says handout, if you drop down on that you should be able to open up the hepatitis B virus decision making tool, let us know if you got any issues, we will also be sending it out again when you get the survey at the end.
Speaker 2: Okay, so we are just going to move to the next slide, which is the polling question, so we are considering Chen who is a 28-year-old, Chinese student, who has just attended the funeral of his father. So the question is should you opportunistically test Chen for hepatitis B.
Speaker 1: And while you are answering that there has been a question asked about whether or not we should be routinely testing people incarcerated.
Speaker 2: Yeah, there is a recommendation that people are, it is actually anyone with a history of incarceration should be tested, considering they are a risk group, so yes, it is a recommendation.
Okay, I think we are going to close the poll. Okay, so basically 94% thought yes, we should test Chen and 6% thought no. So the answer is yes, I mean there are two reasons really, Chen is from China, so he is from a high prevalence country for chronic hepatitis B, actually technically China is probably now intermediate prevalence due to their vaccinations, their prevalence has dropped below 8% but it is still fairly high in the intermediate range. And his father died from a liver tumour, so again you know we often talked to patients about hepatitis B being family business, family business because it often does run in families, not that it is inherited but it has been transmitted from mother to child or in early infancy.
So, to determine hepatitis B status the recommendations in the national guidelines are to order three tests. The first test is hepatitis B surface antigen and that looks for the presence of the virus. Hepatitis B core antibody and the proper way to write it is anti-HBc but if you write core antibody you will also get your result back. That is testing for exposure, has the body ever seen hepatitis B before and hepatitis B surface antibody is testing for immunity. It is recommended that you do not just write hepatitis B serology because sometimes you would just get surface antigens, sometimes you will get surface antigen and surface antibody, and sometimes you will get surface antigen and core antibody. And usually to make the assessment of does this person have hepatitis B, have they been exposed to hepatitis B and are they immune to hepatitis B, you need all three tests.
Testing is covered by Medicare, you know there is sometime a concern if you are doing a screening test is Medicare going to reimburse that, but basically if you write chronic hepatitis B it is not really an issue.
So, this is Chen’s serology, so he is hepatitis B surface antigen positive, he is anti-HBc positive and anti-HBs or surface antibody negative. So, what does this mean? We are just going to go to another polling question. So does Chen have chronic hepatitis B. Is he immune susceptible or immune due to resolved infection. So, we have got a few people who are not sure so we are just taking a little while to let the numbers get over 30% or 40% before we close off the poll, okay we will close off the poll now.
So, of the people who voted, 83% got the correct answer, which is chronic hepatitis B infection, 2% got immune due to vaccinations susceptible or immune due to resolved infection. We are now going to go through the pattern of the serology and look at what it means.
So, Chen’s serology is chronic hepatitis B infection, so let us consider the different serology. This is on the decision making guide, there is a summary. So in hepatitis B surface antigen is the first test you look at, when you get the three results back you look at hepatitis B surface antigen first, if it is positive the person has hepatitis B, if it is negative they do not have hepatitis B and that is your first, sort of, go to in those three collections of tests. Anti-HBc positive just means that Chen has been exposed to the core of the virus, there are different envelopes around the virus and he has not cleared the infection so he is anti-HBs negative. The other test results that appears on your screen includes IgM to core, which we use when we suspect acute infection. For Chen, he was born in China, he is most likely to have chronic infection from early life exposure but if someone came to see you and they had a recent history of tattoo, or had a recent history of an acute hepatitis illness, or you had a documented past hepatitis surface antigen negative test, you would consider ordering anti-IgM for core because that would tell you is it a recent infection or not.
Okay so now this is just looking at the different patterns, so again as you look at these patterns it is good just to look at the surface antigen first, whether it is negative or positive does the person have hepatitis B or not have hepatitis B. Once you have ticked off that question in your mind then you move to the other one, so in the first example at the top, all tests are negative, so this person does not have hepatitis B, has never been exposed to hepatitis B and is not immune to hepatitis B. The second example, again you look at surface antigen first, it is negative, the person does not have hepatitis B but they are both core and surface antibody positive, this is an example of someone who is immune due to resolved infection. Again, the surface antigen is saying negative, they do not have hepatitis B. The core antibody is positive, so they have been exposed in the past and they have surface antibody, so they are immune. The next one is again looking at surface antigen, which is negative, anti-core is negative and surface antibody is positive, so this is a pattern associated with vaccination. So again, they do not have hepatitis B, they are surface antigen negative, they are core antibody negative, they have not been exposed to hepatitis B and there is surface antibody positive which means they are immune. The last serological pattern at the bottom which is surface antigen negative, core antibody positive and surface antibody negative, probably gets way too much discussion generally, okay. The most common reason that you see in this pattern is that someone has had hepatitis B, cleared it and they have just got waning surface antibody. So, the surface antibody has dropped below the threshold of what we say is positive, but they still actually have an immune response and that is probably nearly 2 million people in Australia might have this pattern. The other possibilities are recovering from a recent hepatitis B, so their antibodies are in transition; acute hepatitis B or a false positive and then the last one which everyone worries about the most is the occult hepatitis B. If someone is not surface antigen positive and you organise to do a viral load, that person does get charged under Medicare so again, for this one most people will actually be distant resolved infection and they are essentially immune, it is just that their surface antibody has dropped.
So, for testing and interpreting results, we should be thinking as GPs of opportunistically testing people from priority populations. We should order all three serological tests and we should write ?chronic hepatitis B on the test slip.
Okay, so someone is hepatitis B positive and the next section of this webinar continues on to think about what now, what do we do next? So, there is a range of illness with hepatitis B, acute hepatitis B especially in children but also in adults can be anything from asymptomatic, which is most common through to severe or fulminant hepatitis B which is very rare. Chronic hepatitis B most often is asymptomatic. So, most people living with hepatitis B in Australia will not have any symptoms, they might have some vague abdominal pain, they might have signs or features of cirrhosis and then some will be develop liver failure and some will develop liver cancer. So, it is estimated that about one in five people with hepatitis B will die because of related complications of cirrhosis or liver cancer. This is if they are not treated and if they are not capable.
There is a question about IgM so if we go back to our tests, there is a question just explaining again about acute hepatitis B, so that is if you suspect acute hepatitis B, so if someone has a recent illness, a past history of being negative and now they are positive, a history of jaundice you know in the last six months, they are the kind of times you would do an IgM for the core and again what you are trying workout is this recent infection..
Speaker 1: Somebody is asking in relation to Chen, are we considering acute infection and would we be doing an IgM?
Speaker 2: So if you took a history from Chen and he has no symptoms, he is a well young man, no recent history of illness, you would not do an IgM because again, we have got to remember that story that if he had acquired it as an adult he is 5% likely to have chronic hepatitis B. If he acquired it as a child, he is 90% likely to have hepatitis B or 95%. His father probably had hepatitis B, he had liver tumour, so Chen probably acquired it in early life as a newborn or in early infancy.
Speaker 1: Another question around testing is should we be requesting all three serological tests for pregnant woman?
Speaker 2: Yes, if they come from a risk group, which you would normally screen and this is the first time you are seeing them and screening them, then yes you should order all three tests, so if you are seeing someone from a high prevalence or an intermediate prevalence country and you have no history of hepatitis B testing in the past on that person, you should order all three tests. If they are in their third pregnancy and you have all three tests in the past, and you are seeing them a year later for another pregnancy, then it would be reasonable just to order surface antigen.
So the initial assessment of someone with hepatitis B includes family, a physical examination and then tests, so e-antigen status and e-antibody, a hepatitis B DNA level which is the viral load for hepatitis B, liver function tests, a full blood count, an INR, an alpha-fetoprotein, a liver ultrasound should be done in everyone, and then if you have it available you might also order a fibroscan.
You also test for co-infection so, testing for hepatitis C, hepatitis D which is a defective virus that piggybacks on to B and can only be present in the presence of B and HIV. Testing for hepatitis A is really a question of are they susceptible, because then you would offer vaccination. You would also look at other comorbidities that might affect the liver, including smoking which is not in that list, alcohol, drug use, diabetes, and fatty liver because basically any other risk to the liver could cause further damage and mean more progressed disease. In the initial assessment people are often quite shocked that they have an infection, some people have never heard of hepatitis B, so you need to discuss transmission and prevention, you need to use an interpreter, you need to make sure you talk to people by themselves without their partners or other family members present and then with their consent maybe discuss further with their family if that is appropriate, because really you want to aim to screen that household contacts and their sexual partners for hepatitis B. When we are talking about household contact we are often talking about children, if you have diagnosed a woman during pregnancy, you would want test the whole family living in the house and you often then also have to advise them if their sisters or brothers are living in the country, they should also be tested and certainly their parents should be tested as well. These assessments, the ones we have talked about above help us determine the phase of disease and then make a plan and whether this person is eligible or should need treatment or whether they just need monitoring.
So now we are moving to the decision-making guide and if you want to shift over on the screen on your computer so you can see it clearly, or if you can see it on the slide that is also fine. So, there are four phases in hepatitis B: The early phase, the body is tolerant to the virus, the levels can be extremely high over a 170 million IU/mL. There is no liver inflammation, so the ALT is normal and e-antigen positive and this is the first stage we call immune tolerance. Immune clearance is the next phase and that is when the hepatitis B viral load is still quite high but it starts to come down from the heights of above 170 million and the liver is actually recognising that the virus is foreign and starting to have some inflammation in the liver cells. The ALT might fluctuate up and down. During this phase of infection, e-antigen remains positive. If someone passes into the next stage which is immune control, the e-antigen becomes negative, the viral load drops to less than 2000 and the ALT normalises, which is just the indicator of liver infection. Once this happens, people can stay in this phase for quite a long period of time and essentially their body is controlling the infection and that is why we call it immune control. The final phase is immune escape, not everyone will go into immune escape, but the viral load starts rising and the liver reacts. During the two phases in orange; immune clearance and immune escape, when the ALT is fluctuating as an indicator of liver inflammation are the two phases where liver damage is occurring, and people are eligible for treatment. If they are in immune control but the liver is very scarred through a period when there are in immune clearance, they are also eligible for treatment. If they have no scarring of the liver, they are not, we have got some questions coming in.
Speaker 1: Yeah I do not know if you want to address them now or wait until the end, both are around testing and one is about isolated core antibody and whether or not to vaccinate someone with an isolated core antibody and the other one is around testing a contact and consent. So, I do not know whether you want to continue…
Speaker 2: It might be worth answering them as we go along. So, if someone has got isolated core antibody positive, you do not need to vaccinate them. If they are not immune suppressed, if their liver tests are normal, if there is no other kind of reason, they are not about to go under really heavy chemo-immunotherapy, then you do not really need to do anything, except assure them that they have had hepatitis B in the past and their liver seems to be fine. The second question was, is it mandatory testing for family members, so obviously testing has to be done with consent, so you need both the consent of the person who has hepatitis B to discuss it with their family and then it is up to whether the family members want to be tested. So, testing always follows the five C’s as WHO (World Health Organisation), which I hope I can remember all the five C’s now, which is counselling, consent, confidentiality, correct testing, and then connection to care. So, we always need to counsel people. They have the right to refuse a test. They need confidentiality. They should always be counselled away from family members, including adolescents should not be counselled in front of their parents, they should be counselled separately, and they should always consent to testing.
Speaker 1: I have got another question around, how do you determine if there is liver scarring and the best way of doing that?
Speaker 2: So, liver scarring, there are different ways to test for liver scarring. You obviously first do a comprehensive physical examination and see if someone has any signs of advanced liver disease, so palmar erythema, spider nevi, they might be jaundiced, they might have a swollen belly or ascites. These are very rare. Most people can get quite significant cirrhosis without many physical signs at all. The second way, you can also look for clues in their blood tests, like a reversed AST/ALT ratio or a low platelet, or a high INR, or a low albumin might all cue you to thinking that there is a little more damage in that liver. An ultrasound is not a very good test for screening for cirrhosis, so ultrasounds can be normal in cirrhosis, and if it is end-stage cirrhosis and there is portosystemic hypertension. The other test you can do is an APRI test, which is an aspartate/platelet ratio, which there is a little calculator you can get online, and you can put in the AST and the platelets, and come up with a score, and then the other way you can look for cirrhosis is using something called a FibroScan, which passes a wave through the liver to see whether or not the liver is spongy or not. They tend to be available at liver clinics and some you have to refer in for an appointment before you can get a FibroScan and some you can just refer straight to the FibroScan Clinic. There are other modalities available. There are other tests, bloods tests that are available, and there is also an ARFI scan. And you can check in your local area and ASHM also have some information about that on their website.
So, moving back to Chen, my slides are not moving. This is just an important red flash, that there is no such thing as a healthy carrier. So, a lot of us were taught in medical schools that you could be a healthy carrier. What we think of now is that people are probably sitting in immune control, but they always have the potential to go into immune escape. So, we do not really think of people as healthy carriers. We think of them as having hepatitis B and needing regular monitoring to see if they have liver damage, liver inflammation, or need treatment.
So, let us go back to Chen. So, Chen, who is surface antigen positive, as we already discussed, has these tests come back. So, his e-antigen is positive, his e-antibody is negative. His hepatitis B DNA is 10,000,000 IU. His ALT is 50 and the normal range of an ALT for a male is less than 30. Now, that will vary sometimes in your laboratory, they will have a different range, but it is recognised that it should be less than 30. And someone tests him again three months later, his ALT is 55. So, the next polling question is, which phase of the disease is Chen currently in? So, is he in immune tolerance, immune clearance, immune control, or immune escape? So, we are starting the poll now. It is open.
So, we have about 40% voted, 19% of you thought he was in immune tolerance. So, if we look at his results, his ALT is elevated, and in immune tolerance, we should see a normal ALT. Nearly 40% of you thought immune clearance because he is e-antigen positive, he has got a reasonably high viral load, and he has got an ALT that is elevated.
Speaker 1 You might just go back the slides, so that people can see what we are referring to maybe, yeah.
Speaker 2: Okay. Alright, so he has e-antigen positive, he has got a high viral load. So, e-antigen positive, he is in the first half of the chart. He is either one, immune tolerance or immune clearance. The ALT being elevated is the clue that he is actually in immune clearance, not in immune tolerance. So, again, with his ALT, his ALT should be less than 30 and this doctor or whoever who saw him twice and repeated his ALT, which is something very reasonable to do. It is very rare that you have to start treatment straightaway. So, often you take an initial liver function test and then you might take subsequent ones just to check that you are not seeing a fluctuation, you are not seeing a peak or a trough. So, he is in immune clearance.
So, key points with hepatitis B. There is no such thing as a healthy carrier. Hepatitis B is a chronic disease and it moves through different phases, and patients have to be monitored regularly to determine which phase they are in.
So, now the next and last section we are going to go onto is monitoring and treatment. So, use the Hepatitis B Decision Making Tool to determine which phases are indicated for the consideration of treatment? So, again, we have covered this already, which phases are indicated for treatment? So, you can click more than one answer.
Speaker 1: And while you are answering that poll, we have just had a question, is liver elastography as good as FibroScan to assess cirrhosis of the liver?
Speaker 2: It is really the same thing. It is, elastography is just the sort of proprietary name, FibroScan is really just the brand name, the brand of the machine.
Speaker 1: And somebody else is asking how often treating and monitoring, and I think we are probably getting into that.
Speaker 2: Yeah, I think we will cover that in the next section, and actually, if you look at your decision-making guide on the side without the squiggler-gram, there is how often to monitor, but we will cover that in a minute.
Okay, so, most people have said immune clearance and immune escape, which is correct. If you put immune control, I did say before that if you have got cirrhosis in immune control, you might be under treatment, but in terms of just the phases, only thinking about the phases, we are considering treatment in clearance and escape.
So, this is the monitoring, and this is contained on part of your decision-making guide. So, the monitoring recommended, if someone is not on treatment, is liver function tests every 6 months and a hepatitis B viral load every 12 months. The hepatitis B viral load every 12 months is only rebatable once a year under Medicare and if you order the test in less than 12 months, sometimes the patient will get a bill. What I tend to do is I write on the path slip the date of the last test, you know, say someone was tested on 8th of June and for the next test, I write, not before the 8th of June, trying to put it back on the pathology provider to check that. Okay. If someone is being treated, that might be slightly different how often we monitor them. So, often in the first year, we monitor them more often, every three months, and then once they are stable, and their viral load is undetectable, we tend to only monitor them every six months.
Speaker 1: I have got a question here about monitoring of a patient in immune control phase. Can this done by a GP, or should we be referring to a specialist?
Speaker 2: So, it is a great question because we really should be, we can do this in general practice. So, if someone is in immune control, you are confident they do not have cirrhosis, you would be monitoring, that you could monitor them in general practice, and you just want to make sure they have a yearly viral load. If they fall into a risk group for liver cancer surveillance, and again that is contained on your decision-making guide, so that is a go-to in terms of monitoring and looking after people in general practice, then you might also have them on regular liver cancer surveillance in general practice, but you do not have to refer them. Gradually, in our practice in Footscray, we are trying to make sure all patients, who are in immune control do get a FibroScan. That has actually taken a few years to happen, but that is just gradually happening over time. So, you would consider referring them for a FibroScan if that was available in your local area.
So, the key messages in treatment. So, the first line treatment are tablets; entecavir and tenofovir, and currently, they are under the s100 schedule. So, you have to be an approved prescriber to initiate tablets. Patients take one pill a day and it is usually an indefinite duration. They are fairly safe and well-tolerated and associated with almost no resistance, and treatment is usually lifelong. It is quite important that people do not stop and start treatment. If they stop and start treatment, they can have a dangerous flare in their liver, and so it is important to discuss adherence at each visit, and to make sure if someone presents and they are about to run out of tablets, it is an occasion where if you did not have a prescriber locally, you might try and organise for them to be seen urgently to get that script.
Speaker 1: I have got another question about monitoring and how often a FibroScan should be done?
Speaker 2: There is actually no evidence for how often a FibroScan should be done. It is obviously more of a concern when someone is actually having, you know, if their ALT was raised or changing. At the moment, most liver clinics do them every two to three years, in the community, we are doing them every two years, but there is no real evidence for that. It is probably just as important that someone has just regular ALT and their viral load done because what you are trying to do is you are trying to pick up when they go into a stage where liver damage starts to take place, and then you would treat them and prevent them getting cirrhosis. So, the benefits of treatment are, they get normalisation of their ALT. They get a sustained viral suppression, so their virus might go down to undetectable. Occasionally, people who are e-antigen positive might become e-antigen negative, and they are one group that after a year of treatment, you might consider stopping their medicine because they might be in immune control and they might control it by themselves. Treatment reduces the risk of progression to cirrhosis and liver cancer and reduces the risk of liver cancer by 75%. Very occasionally, about 1% per year, you get someone who loses surfaces antigen and becomes surface antibody positive. This is rare, but someone who is on treatment long-term and his viral load is undetectable, you tend to just check their surface antigen once a year to make sure they are not one of that 1% that has converted in that year.
Speaker 1: And how safe are the treatments in pregnancy and breastfeeding?
Speaker 2: So, for women, tenofovir is the recommended treatment. There is a lot of safety data on tenofovir from HIV, which suggests that there is no, you know, no increased rates of malformations in babies born to women on tenofovir. Entecavir is not recommended, so if you are starting a woman of child-bearing age, who is contemplating pregnancy and you are starting her because of cirrhosis or because she has got liver inflammation, you would choose tenofovir over entecavir, and that is the current recommendation.
Speaker 1: I have got a couple of questions about viral loads and what is considered to be a high viral load, I guess in terms of possibly considering starting treatment, so…?
Speaker 2: Yeah, so, you will see, sometimes viral loads would be reported as log 10 or they will be reported in international units. We tend to now shift towards talking about international units, so if someone is in immune clearance, so that is the second phase, a viral load over 20,000 is considered the threshold for starting treatment. So, you need the abnormal ALT and a viral load over 20,000. Now, the viral load might have gone way higher for that might be into the millions, but you have to be over 20,000. In immune escape, which is the fourth stage, the ALT again has to be abnormal and the viral load should be over 2000 IU, and again that is contained…
Speaker 1: It is actually not. I thought it was but it is not…
Speaker 2: Oh, it is not contained, okay. It is interesting, so that is a different version of the treatment guide, the decision-making guide. We just were looking at the handout, so the old decision-making guide did actually have the numbers on it, but the new one does not. I have to mention that to ASHM next time I speak with them.
Speaker 1: Now, I have got a question. After the initial script being, so, it says after the initial script by a specialist, can a GP prescribe antivirals under s100?
Speaker 2: So, again, you technically have to be an s100 prescriber to prescribe antivirals, either for a continuation or an initiation script. This is something that ASHM has been advocating to change because it is clear that for patients, accessing treatment is really important, and we should encourage people to get scripts wherever they need it, but currently, it is a streamlined authority and you are meant to be an s100 prescriber.
Speaker 1: And you can access a list of GP s100 prescribers online if it is hard to get your patient in to see a specialist of the tertiary hospital? A question about quantitative surface antigen, and whether that is something that we do?
Speaker 2: Yeah. So, it is currently, it is not rebatable. It is essentially a research tool currently, so there is some literature around quantitative surface antigen, and it is important to making treatment decisions, mainly actually when you are using interferon, which is used rarely now, like less than 100 per year. So, we do not quantitate. All that is just, we are normally looking at surface antigen positive/negative, but you can actually quantitate it, and at the moment, that is not something that is rebatable under Medicare and it is not part of the current guidelines.
Speaker 1: A question around breastfeeding in immune control phase, which I think you covered before about how hepatitis B can be transmitted, and whether or not it could be transmitted through breast milk.
Speaker 2: So, yes. It cannot. The advice should be to women is that they can breast feed when they have hepatitis B.
Speaker 1: A question about the efficacy of the hep B vaccination in someone who is immunised, are they 100% protected against hep B infection?
Speaker 2: So, the answer to that is no. Childhood immunisation tends to give 95% protection. If we give vaccinations to adults, especially those over 60, the efficacy of the vaccine tends to drop. So, over 40 and then over 60, there is quite a drop-off in how effective the vaccine is. We do not routinely test everyone to see if they are protected from their vaccination. The exceptions are when there is ongoing risk or exposure. For example, if you are vaccinating a family, where there is someone living with hepatitis B in the family, then you would check at least three months after the last injection, and there are three injections usually over six months to check that that person had actually seroconverted. You would then be able to reassure the person that they could not get hepatitis B, but also very importantly, the person who has hepatitis B in the household, that they need not worry about transmitting it to their loved ones.
Speaker 1: And you have a question about the use of interferon as treatment.
Speaker 2: So, interferon can be used in treatment. It is not particularly, it is only 30% successful at converting someone from immune clearance into immune control, and it has a very small number of people, who are actually s-antigen seroconvert, so basically clear they are hepatitis B. It is a year’s treatment of weekly injections with a fairly low efficacy, so it is not commonly used. It is an option and if someone wants to consider it, they can go and talk with a liver specialist.
GP prescribing for hepatitis B. At the moment, there are 343 accredited GP prescribers. If you are interested in becoming a prescriber, if you have got a number of people in your practice and you are interested in becoming a prescriber, I would refer you to the ASHM website, and there is just a reminder here that for hepatitis C treatments, any GP can prescribe.
So, I think, is this the last polling question? Second last polling question. So, we have established that Chen is in the Immune Clearance phase. Should he be considered for antiviral treatment?
Speaker 1: While you are answering that, we have got a couple of questions around hepatitis B vaccinations and booster doses. Does anybody need a booster dose?
Speaker 2: So, if you have ever had a surface antibody positive, then you do not need a booster dose later in life. Even if your surface antibody drops, it will come back up again, if you are exposed to hepatitis B. I think some examples are if say a young person comes into your practice and they say there are a medical or a nursing student, and they get you to test their hepatitis B, and their surface antibody is negative, you might then boost them and bring them back in a month, just to prove that their surface antibody is actually up high enough.
Speaker 1: And what are we looking at levels there? Is it a level just above…?
Speaker 2: If they are above 10, it is reported as positive. Okay, so basically on the polling question, nearly everyone, 82%, voted right. So, Chen is in immune clearance. He has got a high ALT. He has got a high viral load. He has got a father with liver cancer. He will be having ongoing inflammation, which could cause damage to his liver. So, he should be treated.
Okay, last question, I hope that is it, last question, last time. So, should Chen be regularly screened for hepatitis, sorry, for HCC? So, look at your, on the corner of your decision-making guide, there is a little section on screening for hepatitis, I am sorry, for hepatitis B, I keep on getting it wrong, for HCC, for liver cancer? And there are certain criteria in the corner. So, does he fit one of those criteria? So, should he be screened? No, because he only needs it when he is over 40, or yes, because he has a family history? So, he is 28, if anyone has forgotten.
Okay, so yes, he has a family history. It is sometimes, you know, if his father had developed liver cancer aged 40, you know, some people would say, oh, you have started about 20 years before, I mean, sorry, 10 years before. We usually just tend to start people with screening, or you can discuss that with your local gastroenterologist or ID person about when you should start, but yes, when someone has a family history, they are more likely to have liver cancer.
So, key points in treatment and monitoring. All patients with hepatitis B need to be monitored every 6 to 12 months. So, six months for liver functions test and/or liver cancer screening, cancer surveillance if they fit into one of those risk groups, and 12 months for the viral load. Not all patients need antiviral therapy. Antiviral therapy is targeted in all patients in the immune clearance, immune escape phases, and it should also read, and if they have existing cirrhosis. Entecavir and tenofovir are the first-line treatment and accredited GPs can prescribe antiviral treatment in their community settings. And GPs are essential in ensuring at-risk people undergo surveillance and GPs are also essential in ensuring people are screened and appropriately monitored
So, take home messages, test and diagnose. So, opportunistically test, order the three tests. Vaccination is available for close contacts, family members, and certain risk groups. Check in your jurisdiction what is qualified for free vaccination. Ongoing monitoring. There is no such thing as a healthy carrier. All patients need monitoring and some patients require regular liver cancer surveillance. For treatment, treatment can prevent both cirrhosis and liver cancer, and it can be prescribed by accredited GPs. Now, I have got a few extra…
Speaker 1: Just, just confirming how you go about doing hepatocellular carcinoma screening and what we are ordering to do that, and how often?
Speaker 2: So, it is every six months, an ultrasound and an AFP or alpha-fetoprotein.
Speaker 1: And then, we have got a question about someone who has had past hepatitis B, so that they are core antibody positive, but they are also anti hepatitis B surface antigen positive, so that they have got immunity, and if they are immune suppressed, do they have a risk of reactivation?
Speaker 2: So, for people undergoing severe immune suppression, and that is with a specific drug for treatment for lymphoma, called rituximab, it is possible because there are still very small bits of hepatitis B inside the liver cells. It is possible for those patients to reactivate. It does not happen with what we call regular chemotherapy, but it can happen with a particular drug called rituximab. People who are undergoing chemotherapy generally should all be tested for hepatitis B and people who are surface antigen positive undergoing immune suppression, and this includes chemotherapy, but also immunologic therapy or high-dose prednisolone for greater than a month, so that is greater than 20mg per day for greater than a month. Everyone should be tested for surface antigen. If they are positive, they are also treatment candidates, but that treatment is not rebatable under Medicare, so they need to go through a specialist unit.
Speaker 1: A couple of questions around vaccinations. Someone is wanting to confirm that, if someone has, if a healthcare worker has a surface antibody level less than 10, should we give them a booster?
Speaker 2: So, if you look back through your notes and you never have a history of them being over 10, then yes, boost them and re-test them. If you look back and five years ago, they had over 10, then you do not have to boost and re-test.
Speaker 1: Vaccination of an infant born to a surface antigen positive mother. Do they need to be tested?
Speaker 2: So, they should receive, an infant born to a surface antigen positive mother should receive newborn vaccination and infant vaccination as per the schedule. They should also get hepatitis B immunoglobulin at birth. The recommendation is that three months after their last vaccine, so usually nine months or above, that you test them. At that time, it is the one time you do not do the three tests. You only do surface antigen and surface antibody because they will have persistent maternal anti core antibody. So, you test them. If they have a high surface antibody, you know they are immune, and they do not need further vaccination, and you can reassure the mother.
Speaker 1: And that, just confirming around the booster dose, if somebody has had a course of three, you give one booster and then you can test their surface antibody levels, and only need further doses if they have developed an antibody level above 10.
Speaker 2: That is right. Yeah. That is it. That is it. If they have got it documented three in three. Yeah.
Speaker 1: Hepatitis B cure?
Speaker 2: So, at the moment, there is a lot of investment in cure. So, a lot of researches. Because hepatitis C has now been cured, the attention is turning to hepatitis B. So, at the moment, apart from what we call a functional cure, so occasionally people will convert s-antigen and become negative and positive for surface antibody, and we see that in our practice. We have got about a 130 people living with hepatitis B in our practice in Footscray, and about every two years, that one of the other doctors looking after most of the hep B patients and I, we do see someone lose surface antigen. So, that happens. In terms of cure with drug, it can happen while people are taking tenofovir or entecavir or interferon.
We have got a few more questions. I will just go through the learning objectives. So, I think we have covered off on them; identifying priority populations, ordering tests, interpreting serology, and explaining the need for treatment. Oh, we are doing questions already.
Speaker 1: Someone is just wanting to clarify the percentage of people who clear the virus and develop immunity to hepatitis B, and I think you were referring earlier to dependence on at what age you acquire it?
Speaker 2: So, at what age you acquire it. So, if you look at a baby, a baby exposed to hepatitis B, a newborn, 90% to 95% of them will go onto chronic hepatitis B, 5% of them will be cured, and then if you look at an adult, it is the reverse, 5% of them will go onto chronic hepatitis B and 95% of them will clear the infection.
Speaker 1: And for a sexual partner, someone who is hepatitis B surface antigen positive, they are just wanting to confirm that until a course of three vaccinations has been done and whether or not you have had protected sex, and then confirm, in that situation, is it worthwhile confirming that they have achieved…
Speaker 2: So, a sexual partner is someone who would confirm that they had been successfully protected through vaccination. The recommendation would be for them to use some form of protection until that had happened, but often you are seeing a couple, who have been together for a long period of time, so really you want to test them and then get onto vaccinating them, and each vaccine has the potential to give a certain amount of protection anyhow. So, you would talk about sexual transmission, but actually if they have had a long period of exposure, maybe the chances of them getting hepatitis B over the vaccination courses is low. The other thing to know is if someone is on treatment and their virus is undetectable, it is very unlikely that they can transmit to sexual partners.
Speaker 1: Someone is just wanting to confirm Medicare covering the serology testing.
Speaker 2: So, Medicare covers the serology tests. The only thing you have to be careful with Medicare covers the viral load test, the HBV-DNA, but will only do it once in a year, and it is not like, you know, you can do 1 in 2000, and you have to wait exactly one year for the next test.
Speaker 1: What about stopping treatment? If there are any situations in which you can stop treatment?
Speaker 2: So, the situations where you stop treatment are the 1% of people, who are s-antigen seroconverted. It does happen, but rarely, and if someone e-antigen seroconverted, so you have started them in immune clearance. If they are e-antigen seroconverted, you keep them on hepatitis B treatment for a year, and then you can consider stopping them, although 40% to 50% of them will actually need to be restarted.
Speaker 1: Someone who is hepatitis B surface antibody positive, do they need any monitoring?
Speaker 2: No. So, if someone has resolved infection, they do not need any monitoring. If they clear infection, if they have got cirrhosis, they would need ongoing management of their cirrhosis.
Speaker 1: And do you ever worry about immunity waning in someone who is at high risk and we know that they have achieved a surface antibody level above 10? Do we ever need to check that again?
Speaker 2: So, we do check it in certain groups, like in people on dialysis and people living with HIV, we do tend to check their surface antibody, but for the majority of people, no.
Speaker 1: Great. Well, I think we have answered all the questions. So, thank you everybody for attending. You will be sent through a survey and your points will only be uploaded once you have completed that survey. This webinar has been recorded and you will be sent a link to the recording and it will also be put up online via the RACGP webinar page. Great, yeah.
Speaker 2: Thank you very much for attending and hopefully that was useful. There are some resources that we are just going through now, such as the testing policy. You can go onto the ASHM website and it has links to all of these, and there are resources for patients to your local hepatitis organisation and there is a great resource of Hepatis B Story, which also contains some, you can find it on YouTube as well in different languages.
Good, I think we are about to sign out. Thank you very much for coming.