Amy: Hi everyone and welcome to the RACGP National Webinar Series. I would like to begin by acknowledging the traditional owners of the lands on which this meeting is being facilitated and being accessed by the various participants and pay my respects to the elders past, present and future of these lands. Before we start with the webinar I would like to run through some features to make sure you can interact throughout the webinar. So, we should be able to show a slide now showing where is my Control Panel.
Amy: So, 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 the left, please click on the red arrow to be able to open the rest of the Control Panel and the Control Panel provides you with the tools to select your audio options and is also a place to ask questions during the webinar. You are on mute, but you can adjust your audio.
Amy: You can send questions throughout the webinar and we have allowed time at the end to answer those. We won’t be able to take questions during the content of the webinar. We may also not have time to get to all questions, but we will hope to answer as many as possible. This session does include a case study, but due to the number of people involved and the amount of time we have allowed, we are not actually expecting you to answer some of the rhetorical questions in the case studies. Now, to test this feature, please click where it says Questions to enter a question for the staff and type where you are located today. (Long pause). Okay, we’ve got Canberra, Adelaide, Melbourne, Gold Coast, Tamworth, Wellington Point, Cooktown. This is fantastic! We’ve got people from all over the place. _____Darwin. Excellent. I think now we can use that function now. And we will also move onto the poll test slide. So, we will be conducting some polls throughout the seminar and I am just going to launch the first one now and we would like you to select a colour from below.
Amy: Okay. Over 50% voted. Okay. That’s about 75% of you have voted now. So, we will close that poll now.
Amy: And, blue appears to be the clear winner with 42%, followed by 22% on green.
Amy: I don’t know what that says about our participants.
Amy: Okay, great. So, just a reminder, if you have entered your RACGP number while registering, you will be sent a survey to complete in order to receive your two category 2 points.
Amy: And now we are all familiar with the way that this webinar is going to work. We will get started.
Amy: So, I would like to mention that this webinar is proudly supported by ASHM, which is the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine. Tonight’s webinar is on hepatitis C, cure chronic disease in general practice. GPs can now prescribe new oral direct-acting antivirals for hepatitis C. This offers cure rates greater than 95% with 8 to 12 weeks of well-tolerated treatment. This one-and-a-half hour webinar will present a practical step-by-step guide to the screening, management and treatment of hepatitis C. The session will outline the key questions for hepatitis C testing, diagnosis and assessment and how and when to treat in general practice. I would like to introduce tonight’s presenter Dr David Iser. Dr Iser is a gastroenterologist and hepatologist with an expertise in the treatment of viral hepatitis. He treats people with a range of conditions at both St Vincent’s and the Alfred Hospitals in Melbourne. His interest includes treating people in special populations, such as people with HIV co-infection and people in prisons, and upskilling GPs towards the elimination of viral hepatitis. Thank you very much David and I’ll let you take over.
David Iser: Fantastic. Thank you very much Amy and thanks to the organisers of tonight's webinar sharing the excitement of the treatment of hepatitis C with particular focus on broadening treatment to GPs who are attending a webinar. And a particular welcome to our attendees from all over Australia and I did actually see that we have an international attendee in Samoa. So, that’s fantastic and welcome to tonight's presentation. So, here are my disclosures. It has been a very exciting time over the last couple of years in the treatment of hepatitis C and there have been a lot of new changes and in, sort of, implementing these changes we have given a lot of presentations over the last few years, but there is still plenty of work to be done as you will see throughout the presentation.
David: So, what we hope that you will get out of this presentation is that by the end you will be able to identify who is appropriate for testing for hepatitis C, you will know the tests to request and you will know how to interpret the results. You will know how to assess for liver fibrosis and how to assess your patients for important comorbidities that might influence your treatment decisions and you will be able to have some confidence in deciding which patients you can comfortably treat and which patients still require referral for specialist management. But as you will see, the vast majority of people living with hepatitis C in Australia who need treatment are actually suitable for treatment in primary care, that is, treatment in your practices.
David: So, when the direct-acting antivirals became available on the PBS on 1 March 2016, we estimated that there were about 230,000 Australians living with chronic hepatitis C. And, as you can see by the end of 2017, so just under two years later, that number had fallen from 230,000 to only 180,000. Since the end of 2017 we have treated probably another 25,000 to 30,000, maybe even more. So, we estimate that now we might be looking at about 150,000 Australians living with chronic hepatitis C. But it is important to realise that still one in five of those are 150,000, so up to 30,000 Australians may still be unaware of their diagnosis of hepatitis C. And we know this from various serosurveys that are done over the years, particularly by the group at the Kirby headed by Greg Dore and Gail Matthews and Jason Grebely. So, we are reasonably confident of these data. What you can see from this figure overlying the map of Australia is that around half of those people living with hepatitis C have genotype 1 and about a third have genotype 3 and the remainder is made up of other genotypes. We will talk a little bit in more detail about genotypes later on, but at the moment we still require to test hepatitis C genotype because it’s a requirement by the PBS. It’s one of those bits of information they ask as you are writing a prescription on the 1800 number.
David: So, how do we find that underdiagnosed 20%? So, you are probably aware, because it’s had a fair amount of media over the last couple of years, that in late 2015, the government agreed to fund these direct-acting antivirals for DAAs, and this was a very exciting announcement because we were one of the few countries in the world at that time and even now, to allow anyone with chronic hepatitis C to be treated with government subsidisation. Some other countries restricted on the basis of disease stage, so they may have restricted to people just with cirrhosis or advanced disease, but in Australia, anyone with the virus is eligible for treatment. And there was a lot of media attention given to that initial estimated cost price. So, if you look on the side of the bottle or if you look on the PBS website, you can calculate a cost price up to and around AUD100,000 if you add up those list prices. But in fact we think that the actual cost that the government is paying is only around AUD10,000 per treatment course. So, that is one of the lowest prices in the world and it’s definitely cost-effective, particularly when you consider that treatment of hepatitis C is treatment for cure. And we will talk a little bit about the concept of cure later on.
David: So, where do GPs fit in the role in the hepatitis C response?
David: Well, GPs are vital in screening for hepatitis C, vital in managing people living with hepatitis C and providing treatment, vital in assessing and managing comorbidities such as ongoing drug use, mental health conditions and other chronic diseases. I am sure you are all familiar with managing people living with chronic diseases.
David: Australia is very fortunate, although it was not just good fortune, it was also good planning, in that we did do a fair bit of education of general practitioners leading up to this March 1st 2016, we have tried to include general practitioners in the treatment of hepatitis C prior to the arrival of DAAs and you can see that from this chart when DAAs became available in March GPs made up just a small proportion of the prescriptions written, but as that time has elapsed you can see that GPs are making up a much more significant proportion of those prescribing hepatitis C treatments. In what we have seen in other countries where primary care is not so involved in treatment is that treatment numbers have fallen dramatically once all of those people who were sitting in our waiting rooms on our databases waiting for treatment, once the specialists have treated all of those patients there was no one left to treat and overseas, they do not really have the infrastructure to go and find all these people that were still living with chronic hepatitis C, but in Australia we have a growing body of experienced GPs or interested GPs and GPs with expertise who are treating people living with hepatitis C. So, it’s really important.
David: So, let’s talk about identifying who might be at risk.
David: There’s lots of ways of approaching this. In America, the CDC a few years ago suggested cohort screening where they just suggested anyone born in the baby boomer generation from 1945 to 65 should be tested. What they then found was in fact other birth cohorts had a similarly high rates of baby boomers. So, you could almost make the argument that anyone should be tested and certainly we have a very low threshold for testing someone with hepatitis C, but if we were to target people at highest risk of hepatitis C we would target women who are pregnant as part of their antenatal screening, we would target the partners of people who are known to have hepatitis C, we would target the children of mothers known to have hepatitis C, although not many people would necessarily be aware of their mother’s hepatitis C status, so it is a somewhat problematic definition. We could include it as part of any baseline check. We could include it as part of family planning or prior to travel. We should certainly consider testing for hepatitis C in anyone with abnormal liver function tests, particularly the ALT. We should certainly consider in anyone who is experiencing fatigue or jaundice and anyone who is testing positive for one of the other blood-borne viruses, hepatitis B or HIV, should certainly be tested for hepatitis C. I always try and think of the idea of testing positive for one blood-borne virus should trigger testing for all blood-borne viruses.
David: So, to sort of frame our discussion we have included the case of Tim, who could represent almost anyone in your practice.
David: So, in this case, Tim is a 56-year-old office worker, he is new to your practice having moved into the area, he is describing fatigue, but is otherwise well. He takes no regular medications, drinks minimal alcohol, and during his history he reveals that he briefly injected drugs in the 1980s. Now, I must say, having not written this case myself, I think that’s a pretty odd thing to offer in your first visit to a new GP in a new area. Not many people offer that they once injected drugs in the 1980s, but this may have been on Tim’s mind. Some people injected drugs in the 1980s and don’t even remember it. So, I wouldn’t rely on that as being a trigger necessarily to test for hepatitis C. So, the rhetorical question what to do next. Well, this is webinar on hepatitis C, so let’s test Tim for hepatitis C. So, how we are going to do that?
David: So, we really should be thinking about testing, as I said before anyone who has ever injected drugs, but the caveat being that often people won’t offer that, particularly in their first consultation, they may not remember it. I have certainly seen patients who presented at the blood bank tested positive for hepatitis C, they live in their late 50s or 60s, then when the positive test comes back they remember, “ah yes, I went to that party in the 70s and injected drugs”. So, it’s not necessarily a reliable piece of history to take, but anyone who has injected drugs should be tested, tattoos or body piercings, particularly before the early 1990s, anyone who identifies as aboriginal or Torres Strait Islander or anyone born overseas in a high-prevalence area, and you can see there we have included Africa, particularly Egypt, where in some cohorts the rate for the prevalence is as high as 20%. The subcontinent including India and Pakistan, Mediterranean and Eastern Europe. The rest of Africa and really anywhere in Asia, even the Pacific. We haven’t included in this presentation, but we should remember that every year there are still 1.5 million new infections of hepatitis C. So, hepatitis C is still being spread, particularly in other parts of the world.
David: We should also test anyone who has had sex with a hepatitis C positive person. Again, the caveat is that not many people are aware of their hepatitis C status or disclose it when having unprotected sex. But particularly men having sex with men or men known to become infected with HIV and hepatitis C. We have probably treated most people who receive blood transfusions before 1990, but not all. I have talked about the caveats of knowing your mother’s hepatitis C status, talked about ‘see one blood-borne virus, test for all’. I have mentioned anyone with an abnormal ALT, and remember that our normal ranges are not true normal. So, the true normal is the upper limit of 30 for men and 19 for women. So, you may even see someone who is complaining of fatigue whose ALT is 35 that fits in with your laboratory’s normal range, but it’s actually not a true normal and certainly anyone after needle-stick injury should have testing for hepatitis C.
David: So, that brings us to polling question 1.
David: So, polling question 1. Which of the following is not a mode of transmission for hepatitis C: And our options are sharing personal hygiene, experiencing traumatic unprotected sex, having unsterile tattoos or body piercing, sharing injecting drug use equipment or sharing cutlery or cups. So, you should be able to poll now, and you are polling, good, up to about 70%, that might do. So, let’s see how we went.
David: That’s right. So, sharing cutlery and cups is not a way of transmitting hepatitis C. Hepatitis C is basically a blood-borne virus, so you really need to share blood to contract hepatitis C. Having said that hepatitis C is in semen, so if you are engaged in traumatic sex where there is mucosal breaks it can get into the bloodstream and that is how we think hepatitis C is transmitted through sex.
David: So, very good. I must say my sort of adherence to enquiry about hepatitis C transmission risks has declined as hepatitis C treatment has become easier. I am interested in treating hepatitis C and then preventing reinfection and that will generally be via unprotected traumatic sex or via injecting drug use. I am interested in when someone may have acquired hepatitis C, but it should also be remembered that somewhere between 15 and 20% of people with a diagnosis of hepatitis C actually don’t report any known risk factors. So, sometimes we can sort of wind our self up in knots thinking about how someone may have acquired hepatitis C, but the more relevant point is they have hepatitis C and can be treated and cured.
David: This is a busy slide and we’ve talked about most of the important points on the slide. Maybe something we haven’t mentioned is that mother-to-child transmission is uncommon, but not impossible. So, we think the mother-to-child transmission risk is somewhere between 3 and 5%. Now, that sounds low, but I have said that figure to a pregnant woman and watched her burst into tears because 3 and 5% to someone with hepatitis C who is pregnant can sound catastrophically high. So, it’s a different number depending on who you are I guess. The risk of heterosexual transmission in stable couples is pretty low. I have estimated it about sort of 1% per year in a landmark Italian study from several years ago. Whereas in men having sex with men it’s much higher. Men having sex with men where the men have HIV as well, it’s even higher up to about 10% to 15%. In the presence of other STIs it’s higher, so syphilis with a mucosal lesion can dramatically increase the risk of transmission. Household transmission is pretty uncommon. We have come across transmissions through sharing of razors, toothbrushes theoretically but razors certainly, but sort of normal body contact, hugging and kissing, cutlery and crockery, that’s not a risk. Breastfeeding, it’s difficult to get data around breastfeeding, but it’s not recommended if you can see blood or if there are cracked nipples, but otherwise it should be okay.
David: So, back to Tim. So, he declared a history of having injected drugs, so we should definitely test him for hepatitis C. So, what do we request?
David: So, testing and diagnosis of hepatitis C.
David:So, we have a polling question here again. And the question is. Which tests would you order?
David: So, would you request antibody and genotype or do you request antibody and hepatitis C RNA if the antibody is positive, would you just request genotype, would you just request antibody or would you just request RNA? This one requires a little bit more thought and I can see you giving it a little bit more thought, which is great. So, up to about almost two-thirds. So, we might close it there and talk about the results.
David: Yeah. So, most of you got it exactly right, which is you request the hepatitis C antibody and the you request the hepatitis C PCR if the antibody is positive and you can actually do that with one bleed. If you request hepatitis C antibody and then put in brackets if positive, please do PCR and genotype. That way when the person is undergoing the blood test the venipuncturist will take two tubes, one for the serology, the antibody and one for PCR and genotype and the person won’t have to come back for a re-bleed, the laboratory will do it all for you. So, that is something you can do as GPs and it certainly saves an extra bleed.
David: If you just asked for PCR, they would probably refuse it because they will only do it if the antibody is positive. So, often this remains confusing and it’s something you probably have to read or hear a few times before it sticks. Think about the antibody as just a signpost that the virus leaves behind when it is in the body. It’s basically saying “I was here”, it doesn’t tell you whether or not it is still here. So, to decide whether or not the virus is still there you need to test for the actual virus, which is the RNA by PCR. And we have talked about the people in whom hepatitis C antibody should be tested.
David: So, Tim's antibody test not surprisingly is positive. So, what does this mean? That means he once upon a time had the virus, doesn’t tell us whether he still has it, but as I am sure you can guess that this being a webinar on hepatitis C, he will still have it. About 45% of young women will actually spontaneously clear hepatitis C. About 15% of older men with HIV will spontaneously clear hepatitis C, and anyone else is somewhere between that 15% and that 45%. So, spontaneous clearance without treatment of hepatitis C certainly occurs and that’s why we need to do the hepatitis C RNA by PCR rather than just treat everyone. Overall, the spontaneous clearance rate is about 25%.
David: So, antibody positive and RNA positive, that means that someone still has hepatitis C and qualifies for treatment. If the antibody is positive and the RNA is negative that means they have had spontaneous clearance. If the antibody is negative that means they’ve never been infected with hepatitis C. The caveat is that you could have someone who infected themselves with hepatitis C 12 weeks ago remains antibody negative, but their liver tests are all over the place and if you asked for a hepatitis C PCR that would be positive. So, that’s a special setting of acute hepatitis C, just worth having in the back of your mind, but basically start with the antibody, also request the RNA and then you’ll be able to interpret the results.
David: So, if we are suspecting hepatitis C we might also like to do some other blood tests, that would include full blood examination, liver function tests, urea and electrolytes for renal function, clotting is probably an optional extra, C1 blood-borne virus test for them all and we have included hepatitis A as a hepatitis virus as well, and then pregnancy tests for women of childbearing age. If we are considering treating someone for hepatitis C we want to make sure that a woman is not pregnant first.
David: So, just a brief slide on hepatitis B serology. This is an area that I found as a student, I used to have to come back to every six months and every six months I looked at this slide and it was as if I was learning it for the first time, and I suspect there are others in the audience of several hundreds who are in a similar position, but basically with chronic hepatitis B, you need to ask for three tests in order to work out what someone’s hepatitis B status is. So, you asked for a surface antigen and that tells you whether or not they have chronic hepatitis B. So, surface antigen positive equals chronic hepatitis B. Someone who has a positive surface antigen will always have a positive core antibody. Those two will go together and it equals chronic hepatitis B and you then go on and assess for chronic hepatitis B, which is the topic of a different education evening. Their surface antibody will be negative. Somebody who is negative for all three tests, they are hepatitis B susceptible and should be vaccinated for hepatitis B. Someone who has positive anti-hepatitis B core antibody and anti-hepatitis B surface antibody is immune to hepatitis B through prior infection and subsequent clearance, so they don’t need any further testing or any further vaccination. They are immune. If they were ever exposed to hepatitis B again they would not get acute hepatitis B. Isolated positivity to core is a complicated scenario and probably not worth going in too much detail, but you could consider consulting a specialist. There are a variety of scenarios that could be represented here. The most common scenario is that they will have a positive surface antibody, so that’s immunity to chronic hepatitis B and that’s being achieved by vaccination. So, sometimes it helps to just try and derive that table yourself by first principles in about a week and see if it sticks and if it doesn’t go back and try and make sense of it all beginning with the surface antigen, meaning chronic hepatitis B. The relevance in a talk or a seminar on hepatitis C is that if someone has got hepatitis B C dual infection that is probably still a reason to refer to a specialist. We have also seen rarely reactivations of surface antigen negative chronic hepatitis B with positive core after the hepatitis C has been successfully cured. It is rare but it has happened and so that’s really the relevance of this little minute or two on chronic hepatitis B.
David: So, Tim’s results. So, you can see with his FBE that probably the most important result here is that he has a normal platelet count of 270, not just normal but middle of the normal range between 150 and 450. We often worry about people with low-normal platelet counts of sort of 160, particularly if they have been declining over the past few years, because that may actually predict the development of portal hypertension and the presence of undiagnosed cirrhosis. Tim also has normal renal function, which is important because some of our medications are cleared by the kidneys. Tim has returned a pretty reassuring set of liver function tests. You can see that his albumin is at the lower end of normal range of 36, bilirubin normal at 16, just mildly raised ALT and AST of 52 and 46 respectively. Slightly raised GGT which could be from all sorts of causes, hepatitis C is one of them, but maybe a little bit of fatty liver disease or a little bit of alcohol, although I think Tim didn’t drink much. ALP is normal in probably most laboratories. You will be far more expert with his lipids, but the triglyceride looks a little bit high. He has got enough HDL and his fasting cholesterol is within the normal range for most laboratories. It was probably below the threshold for treatment, but there is the important one, his hepatitis C RNA is positive. So, without knowing anything more about Tim, he qualifies for treatment. That’s all you need for treating hepatitis C in Australia, is a positive hepatitis C RNA. So, importantly here Tim is immune to hepatitis B through prior vaccination, is negative for HIV and he is also immune to hepatitis A possibly through his previous combined hepatitis AB vaccination or maybe through previous subclinical infection. So, what else should we consider? Good question.
David: Let’s assess Tim further for treatment, but so far from what we know about Tim, there’s actually not that much else that we need to assess him for. We still required as I mentioned earlier to do a hepatitis C genotype with good viral load there. It’s not a requirement on the PBS and it’s becoming less important, but historically we have always measured viral loads in any blood-borne virus B, C, HIV, so it’s still there, although as you will see later on it’s of less importance. We need to use those results that we’ve got already plus our clinical history taking and examination to decide whether or not Tim has cirrhosis and make an assessment of his liver disease stage and we have already taken a bit of a history from Tim in terms of comorbidities and alcohol consumption, but we will do this in more detail.
David: So, we will go to the second point initially, so just talking about the staging of liver disease. So, as you probably recall liver disease can be staged from mild fibrosis or normal liver through to mild fibrosis, moderate fibrosis, severe or advanced fibrosis through to cirrhosis. And what that’s really referring to is the degree of scar tissue or collagen outlined there in blue or blue on the slide here, within the liver parenchyma within the liver tissue. Cirrhosis is where you have lost your normal hepatic architecture. You are starting to see such disruption to the normal hepatic globules and such large tracts of scar tissue that the liver no longer looks like a normal liver and that’s a really important diagnosis to make, especially when we are considering treating hepatitis C, because even after cure of hepatitis C we will need to follow these people indefinitely. It is also somewhat important because it may change the length of treatment. It may also in some cases change our choice of treatment. Basically, the message we want to give is that if you are suspicious of cirrhosis or if you diagnose cirrhosis, we still want these patients to be referred to liver specialists to treat the hepatitis C and manage their cirrhosis. There may be situations and I noticed in the initial poll question that there are a lot of people from regional centres and may be situations where it’s just impossible to get access to a liver disease specialist or your patient may absolutely refuse to go to a gastroenterologist because of stigma or bad experiences in the past or cost or whatever, and we do still prefer that these people are treated for hepatitis C. Sometimes this is done in conjunction with a liver specialist by telephone or email or through some other communication channel. Personally as a gastroenterologist I would much rather these people still received treatment for their hepatitis B, but we would prefer to see them in specialist care if possible. I mention there the long-term follow-up after cure, which includes surveillance for hepatocellular carcinoma or HCC. At the moment cirrhotic status is still required along with genotype for PBS approval and that is unlikely to change. Genotype may disappear, but cirrhotic status is still going to be required.
David: So, how I mentioned clinical history taking and examination as a preliminary way of assessing liver fibrosis and by that I was alluding to the fact that pre-test probability, if you like, is a really important parameter when considering someone's likelihood of cirrhosis. For instance, if you saw someone who had had hepatitis C for 40 years, had drunk hazardous amounts of alcohol for similar length of time, was covered in spider nevi, starting to look a little bit jaundiced and yet your FibroScan came back as a non-cirrhotic FibroScan, of let’s say around 8, I would still be suspicious that this has cirrhosis, and that’s because your pre-test probability is so valuable. If you look at it from the other end of the spectrum, if you saw a young woman who had had hepatitis C for one year, had a little bit of inclination with a raised ALT, but didn’t drink alcohol, was slim and otherwise fit and healthy and a FibroScan came back with a cirrhotic reading, I would disbelieve the FibroScan and be guided by your physical examination and your clinical suspicion. So, I guess what I am trying to illustrate here is that no one test is accurate enough to overturn all the rest of your data. So, we really need to look at all of these things together, your history, your examination, your laboratory tests, and using the laboratory tests we can perform a simple calculation called the APRI score, which we will go on to in the next slide. An APRI stands for AST to platelet ratio index. It’s basically looking at the degree of inflammation measured by AST and note that it is AST because a lot of laboratories won’t test that unless you request it specifically. So, AST compared to the normal range for your AST divided by your platelets. Conveniently, less than 1 makes cirrhosis incredibly unlikely, more than 1 can’t rule out cirrhosis, so we need to go onto some sort of further test, which may be FibroScan. Now, I am not sure whether all of the attendees will have access to FibroScan. You’ve probably heard of it, and it is probably hiding in an ivory tower in your nearest tertiary referral centre. There are some in the community, or an increasing number in the community. They do often visit from tertiary centres. There are a lot of mobile scans in the community. A lot of private radiology centres have started to introduce shear wave elastography. It is similar to FibroScan, the cut-offs are all a little bit different. There are caveats involved, but it’s probably measuring the same thing and it’s probably going to turn out to be reasonably reliable. Ultrasound is very useful if it shows cirrhosis, and we will go onto that with one of the polling questions, but it’s not particularly sensitive for cirrhosis. In some settings it’s sensitivity is only around 50%, so no better than a coin toss, but if it does actually shows cirrhosis with nodular liver edge, signs of portal hypertension then that’s a useful diagnosis to have made on ultrasound.
David: So, the APRI… if you don’t have access to APRI on your smart phone there is an APRI calculator at this website for you that I will show you on the next page what an APRI calculation looks like.
David: I mentioned AST divided by the upper limit of normal, which depending on the laboratory is somewhere between 35 and 45, divided by the platelet count. So, you can see that if your AST is very high, say 200, and your platelet count is getting low, you will end up with an APRI more than 1. Whereas if your platelet count is preserved, say with Tim's it was 270, and his AST from memory was around 40 something, it will come out as less than 1.
David: In fact let’s see if we have got it. Here it is, so 46 divided by 40, all divided by 270, multiplied by 100 gives us an APRI score of 0.4. So, we can be very confident that Tim does not have cirrhosis and does not really need any further assessment for cirrhosis. He does not need an ultrasound. This may be different again if Tim had been someone with a long history of heavy alcohol, covered in spider nevi and a 40- year history of hepatitis C, you may look at the APRI and still be a bit suspicious and go on and do something else. That’s coming back to that point I made earlier that no single test is completely reliable, but in Tim, this is a pretty good way to exclude cirrhosis.
David: FibroScan if you have it available is a measure of liver stiffness, you can see here that it looks like an ultrasound probe. On the end of that probe it’s got a little protrusion that flicks. The patient actually feels a little flick, it’s not painful, it feels like flicking yourself with your middle finger. You can see on the screen there. There is an elastogram that gives us a measure of the speed that the ultrasound waves travels through the liver. A stiff liver will transmit that little vibration very quickly, you will get a high liver stiffness measurement, and you will diagnose with reasonable confidence the presence of cirrhosis. A normal elastic liver is a bit more like a ball of jelly, you can imagine flicking a ball of jelly, the vibration travels fairly slowly through the ball of jelly and you will get a low liver stiffness measurement. So, it’s pretty good at the ends of the spectrum, it’s not so useful in the middle, like many tests in medicine.
David: So, polling question 3.
David: Which of the following findings is least suggestive of cirrhosis. So, an APRI score of 1.9, a FibroScan showing a median liver stiffness measurement of 15, which is high, and ultrasound showing coarse echogenicity. An examination showing big spleen, ascites, and spider nevi or a platelet count of around 100, a prolonged INR and a low albumin. So, which of the following is least suggestive of cirrhosis. So, most of them will be suggestive, one of them less so.
David: Very good, so we’ve got about two-thirds voted now and it looks like most of you, almost half have got the correct answer, which is that an ultrasound showing coarse echogenicity, as you know it’s an incredibly common report and it’s more likely to reflect fat in the liver, either from alcohol or from non-alcoholic fatty liver disease, say, in the setting of obesity or diabetes. Platelet count of a 100 with a slightly prolonged INR and a low albumin, I would be pretty suspicious of cirrhosis because otherwise you are having to hypothesise two or three separate conditions. FibroScan showing a liver stiffness of 15, you are right in that some people with that measure may not have cirrhosis, but it is still pretty suggestive unless there is a lot of inflammation going on or unless the person is significantly overweight. So, a slightly tricky question, but most of you got it right.
David: There may have been another poll, I will just go back a second, hold on.
David: Ah yes, so just another FibroScan question. So, how would you interpret a FibroScan result of 8. So, you probably can remember the colourful slider showed a couple of slides ago, but cirrhosis is anything above 12.5 where we get measurements up to 75 before the machine cuts out, and normal is anything less than 7 or strongly suggestive of the absence of cirrhosis is less than 7, normal is up to probably between sort of 3.5 and 5, and a result of 8… look, it’s a bit tricky without me showing you the original slide and we have got about two-thirds of you voting. So, we might leave it there.
David: Look, about half had said moderate fibrosis, which was correct, half of you have said none or mild, so actually I am going to go back and show you the slide, because I’ve had a sudden doubt.
David: So, there you go, so between 7 and 9.5 is actually moderate. So less than 7 is absent or mild, but it was pretty tricky because we put it right near the cut-off. So, those of you who said moderate… look, we didn’t even say it on the graphics, so we have said significant, which is a synonym for moderate. So, a very tricky question, I am not responsible. Apologies.
David: Let’s go onto….that’s sort of summary slide of assessing liver disease. So, as I said earlier no single tool is accurate enough, you need to include your clinical history, your clinical examination as your sort of pre-test probability, and AST to ALT ratio where the AST is progressively climbing relative to the ALT, that may be strongly suggestive of advanced disease, although if someone is drinking heavily that can also elevate the AST preferentially. I mentioned earlier the low platelet count, even the low-normal platelet count, platelets approaching sort of 160-170 may be meaningful. APRI over 2 certainly suggests cirrhosis, APRI between 1 and 2 raises the possibility, FibroScan above 9.5 suggests severe or advanced fibrosis, about 4.5 suggests cirrhosis and if you are seeing signs of cirrhosis or portal hypertension on ultrasound that’s meaningful. If you don’t see them it doesn’t necessarily exclude cirrhosis. So, splenomegaly, enlarging portal vein or a nodular liver edge we haven’t mentioned there, especially ascites is a more obvious one if you are seeing ascites on ultrasound, but would also strongly suggest cirrhosis.
David: Alcohol use is important. So, as you all know alcohol use is incredibly common in Australia. Safe alcohol guidelines being reduced almost every time you look. The WHO recently came out and said that there’s possibly no safe level of alcohol and I have recently come across signage in California, which is maybe a bit more litigious than Australia where they say in every bar and restaurants that no amount of alcohol is safe and if you are pregnant it might harm your baby. So, I think there is probably still lessons to be learned with alcohol. In terms of treating hepatitis C drinking alcohol is not going to impact on our chance of curing someone's hepatitis C, but hazardous intake may go on to cause significant liver disease even if we cure the hepatitis C. I try not to be sort of too dogmatic about alcohol, particularly in the first consultation I don’t want to put the patients off and lead to them never coming back. I might introduce it later on as an important concept, particularly if I am worried that they are at risk of ongoing liver disease, but it is certainly not a reason not to treat hepatitis C.
David: So, what we know about Tim so far. We think he was infected back in the 80s from his brief period of injecting drug use. We haven’t yet seen his genotype of viral load, although as I said earlier his viral load is not particularly relevant. We are confident he doesn’t have cirrhosis with a low APRI score, he doesn’t drink and he has got no other known comorbidities, he is not currently infected with hepatitis B or HIV, he is on no other medications which is important, he has never been treated for hepatitis C before and we are not worried about doing surveillance for hepatocellular carcinoma.
David: What else would we like to know. So, he is the genotype 1a. So, I mentioned in that first slide that genotype 1 is the most common genotype in Australia at around 50%. I forgot to notice the subtype. We should take it out because it is no longer relevant. The laboratories will still report subtypes, they’ll tell you 3a, 3b, 1a, 1b, but it’s no longer at all relevant. In the old days of interferon and some of the early DAA regimens it had some relevance. So, we are still required to report that genotype to the PBS when we called up the 1800 888 333 number and we are still required to tell them that he is non-cirrhotic. So, what else should we do? Should we treat him? Well, the answer is obvious, we should all treat Tim or anyone like him, particularly if he is interested in treatment.
David: So, in terms of other things we might like to know about Tim, I mean Tim is deliberately fairly straightforward, but I should point out that a lot of the people who are coming forward with a new diagnosis of hepatitis C are much less straightforward than Tim and much less straightforward than the people we treated over the first three years. So, they will often have slightly different ideas about health in general or liver health specifically. They will often have different ideas about hepatitis C. They maybe people who have experienced severe stigma and discrimination through their lives, I mean that could apply to anyone who has had a diagnosis of hepatitis C, but personal experience and other conversations with peers is that people presenting now have often had extreme discrimination and stigma, and that is why they haven’t come forward in the first two years of DAA therapy being available. They may be concerned that because they are still drinking or still injecting drugs that they may not be suitable for treatment with hepatitis C, but we need to reinforce safe injecting behaviours and safe drinking behaviours, but we shouldn’t let ongoing injecting or heavy drinking be a reason not to treat someone and we need to make that clear to people. We should offer needle and syringe programmes if they are not already accessing these. We should think about opiate substitution therapy if they are not already accessing OST. We should also vaccinate for A and B if they are not immune. We will talk a bit more about other concomitant medications in a moment.
David: So, I sort of touched on stigma and discrimination, I am not going to show you this video, which is a very good video, but goes through about 5 minutes, but you can see the link there and you should be able to access it at a later date. Even if you just put into Google ASHM Hepatitis C Stigma and Discrimination I am sure this will come up on Vimeo, but I am yet to meet someone with hepatitis C who has not experienced stigma and discrimination, particularly those people who were diagnosed, like many of our patients who were diagnosed in the 80s, many of them were told that their virus was incurable, they were going to die and basically go away, don’t drink and we are sorry there is nothing we can do, and they will have all known someone who has died from hepatitis C. So, they may come bearing a lot of baggage related to the diagnosis of chronic hepatitis C and that’s just something to be aware of. We are trying to turn stigma and discrimination on its head and to give hepatitis C a positive stigma in that hepatitis C is the only curable virus. It’s also one of the few curable chronic diseases. So, if you have to get a blood-borne virus in 2019 hepatitis C is a pretty good diagnosis to get because it’s curable with a short course of medications, which don’t cost much money. So, you might like to just think about why is that you could reduce stigma and discrimination in your practice. I mean, I think about in our tertiary practices, even the naming of a clinic, hepatitis clinic, I think comes with a bit of stigma and we have tried to remove that wherever we can.
David: I mentioned earlier that hepatitis C transmission and reinfection remains an issue. It shouldn’t be an issue that we used to lead us not to treat hepatitis C. I have often heard my colleagues, particularly Greg Dore, say that if we are not seeing hepatitis C reinfection, well, we are treating the wrong people. The idea behind that statement is that in order to have a big impact on the hepatitis C epidemic we need to be treating people who are still injecting drugs and they are the people who will be at risk of reinfection. So, what we have been gratified in seeing is that reinfection rates are very low, but we shouldn’t be put off by the risk of reinfection, because that actually tells us that we are treating the right people. What it does tell us though is that we need to do more than just treat chronic hepatitis C. We need to remind people of safe injecting practices, so that’s not just clean needles and syringes, but also clean other injecting equipment. We need to be treating people’s social injecting networks, that’s very tricky, I understand that networks of people who inject are often just that their networks of people who inject and these people may share nothing else other than the act of injection. They may not be friends, they may know nothing else about each other and may just get together infrequently or frequently to inject. So it is often very hard when you are seeing someone who is still injecting and you are suggesting that all of their injecting partners should be treated. It’s often hard to turn that into sort of practical action and I guess the message is just that we should be treating as many people with hepatitis C as we can.
David: So, I mentioned earlier that the risk of reinfection was low in many of the studies of people with hepatitis C alone, that reinfection risk was less than 1% in studies of people at high risk of reinfections, that’s people injecting drugs or people in prisons where they don’t have access to clean injecting equipment, but where we know that injecting still goes on in a similar rate, the risk of reinfection is much higher. In some of the studies of men with HIV and hepatitis C coinfection that rate is even higher. I guess that tells us that changing sexual practices is often more difficult than leading to changes in injecting practices.
David: So, let’s talk about initiating treatment for Tim.
David: So we have another polling question here.
David: So, I think we have already answered this, but would you recommend hepatitis C treatment for patients with chronic hepatitis C who are on opioid agonist therapy or opioid substitution therapy or who are currently injecting drugs. In the old days of interferon there was a time where we were reluctant to treat people who are still injecting.
David: That changed towards the end of pegylated interferon lifetime, I think and there are still people who hold the view that we shouldn’t be treating people who are at risk of reinfection, but as you have pretty much all correctly assessed, people who are on opioid substitution or are still injecting and at risk of infection should definitely be offered treatment with direct-acting antivirals, DAAs.
David: So, the main message is that anyone with hepatitis C with a positive PCR is eligible for treatment. The one caveat I guess is people who are expected to die from some other condition within the next few months. So whether that’s six months or 12 months you could argue that if someone is facing imminent death from some other incurable condition that treating the hepatitis C is probably not going to make that much difference to the quality of life and therefore probably not worthwhile, but they are about the only people who we should not consider treating for hepatitis C. So, huge benefits, we have talked about the benefits to the population where we can reduce the risk of transmission from people who are still injecting drugs, and this goes to the WHO elimination goals, which we haven’t really sort of talked about, but hepatitis C is one of those conditions where we should be able to eliminate it as being the currently significant public health problem that it is. Whether we will actually be able to eradicate it like smallpox or polio in some areas is a bit more debatable, but we should be able to eliminate it as a public health problem. The benefits to the individual, well, it reduces liver disease progression, so prevents cirrhosis, even in people with cirrhosis it can lead to cirrhosis regression, reduce their risk of decompensation, prevention of cirrhosis can certainly reduce the risk of hepatocellular carcinoma HCC. We don’t really sort of talk about the risk of hepatitis C and HCC, but curing someone’s hepatitis C can reduce all of the risks of chronic liver disease, including HCC. It doesn’t mean that you don’t need to get doing surveillance in someone with cirrhosis, but it certainly does reduce the risk.
David: So, treatment as I alluded to is incredibly easy and effective.
David: So, let’s talk a little bit more about treatment.
David: So, all of the treatments are all oral.
David: There are very few side-effects which we will go into in some detail.
David: All of the treatment courses are incredibly short and for all the patients you are going to be treating treatment is either 8 or 12 weeks.
David: There’s basically no monitoring while they are on treatment. We do some monitoring which we will little talk about at the end of treatment and three months after treatment, but there’s really no monitoring while they are on treatment other than picking up their prescriptions and have no complaints.
David: The cure rates are over 95% in most groups.
David: And in the vast majority of people we really do see a tangible improvement in the quality of life, whether that’s the disappearance of their fatigue, nausea, their mood disturbance such as depression or anxiety, or more subtle improvements such as improved sleep quality and just improved energy levels, in most people we see some sort of tangible improvement and that’s why again treatment should be offered to everyone with chronic hepatitis C.
David: So what can Tim expect to experience?
David: Well, we would hope that Tim will experience an improvement in his fatigue. I think that was his presenting complaint. So, let’s document about the details of what is actually available on the PBS. If you’ve got a bit of spare time and sitting at a computer with access to the PBS, it is worth just clicking on one of these medications. So, for example, sofosbuvir, bringing it up in the search field of the PBS clicking through the authority link and going to the table that we still have in terms of which medications are useful for which genotypes, the reason it’s worth doing is it is still a very confusing mess. So, what we have tried to do in these slides is make it much simpler. And I think if you are new to the treatment of hepatitis C you could make a pragmatic decision to just learn about two medications. You could just learn about those two medications which are pangenotypic, that is Epclusa which is sofosbuvir/velpatasvir, one pill once a day for 12 weeks. The other pangenotypic regimen is glecaprevir/pibrentasvir or Maviret. It is three tablets once a day with food for eight weeks. There are some genotype-specific medications which are fantastic medications, again side effect free, again incredibly high rates of cure, and very useful, but as you see here sofosbuvir/ledipasvir or Harvoni is only indicated for people with genotype 1. And for Zepatier grazoprevir /elbasvir is only indicated for genotypes 1 and 4. So, if you were new to the space and found it difficult to delve into all the details regarding genotype, it would be reasonable and pragmatic to just focus on these two pangenotypic regimens, but we include these because they are great medications and they may be the best option for your patient depending on drug-drug interactions or something else that’s going on in their life. So, definitely worth knowing about if you have capacity.
David: There is also another regimen that you will see down here sofosbuvir/daclatasvir, that’s two separate tablets, it’s on the PBS for genotype 1 and genotype 3. For some patients, depending on their drug-drug interactions, particularly for those people with HIV, that may actually turn out to be your best choice, but back to keeping it simple pangenotypic regimens sofosbuvir/velpatasvir one pill once a day for 12 weeks with or without food or the glecaprevir/pibrentasvir Maviret three tablets once a day for eight weeks with food. And you can see there that people with cirrhosis for Maviret need 12 weeks, but remember we are not suggesting that you start treating people with cirrhosis. So, that’s why that table is there for interest value only. For people without cirrhosis we are just looking at eight weeks of Maviret or 12 weeks of Epclusa, Harvoni there is eight or 12 weeks. I will show you in the next slide why eight weeks is still an option for some people, and the Zepatier grazoprevir /elbasvir there 12 weeks one pill once a day. Daclatasvir/sofosbuvir, again the two separate pills for just 12 weeks. This one down here is not on the PBS, it’s a triple regimen with one pill and it is going to be probably reserved for just salvage therapy, so people who failed previous therapies. Probably should make this point that for all of the people we are intending GPs to treat, we want to actually limit it to people who haven’t been treated with DAAs before. If someone has had a DAA regimen and it has failed we should probably see those in specialist centres because it may be more complicated. If someone's been infected with hepatitis C, treated say with Harvoni here two or three years ago in 2016, cured and then gets reinfected with hepatitis C, that’s not a treatment failure, that’s actually a reinfection, so we are happy for you GPs to treat re-infections, but if someone has had a previous treatment and it did not work and you are suspicious of treatment failure, that’s someone where we actually want to see the patient in a specialist centre because that could be a bit complicated. But for these people we are talking about naïve to treatment with no cirrhosis.
David: So it’s difficult to separate Maviret over here glecaprevir/pibrentasvir from Epclusa sofosbuvir/velpatasvir and we have made it even more difficult by flipping the sides. I think the slide earlier showed Epclusa over here and Maviret over here. So, it is very difficult to differentiate it, it may come down to just personal choice, someone may be really keen for eight weeks’ treatment, someone over here may only want to swallow one pill a day instead of three pills once a day. But the main differentiation may be in their concomitant medications. Epclusa can’t be used in people with severe renal impairment, but we are not imagining that you are going to see many people with severe renal impairment where you are going to be treating the hepatitis C. The similarities are that they are both pangenotypic, adverse reactions are mild headache and fatigue and I think we show on the upcoming slide some of the other….
David: …there we go…. they are the adverse effects. So, all very similar. It’s really four things headache, fatigue, nausea and diarrhoea, and it should be said that these side effects or adverse effects are listed, but in all of the clinical trials, the rates were pretty similar to placebo, particularly in many of the Zepatier trials, where the rates were numerically almost identical to placebo, and in some arms, the placebo rates of these side-effects were actually numerically higher, although it didn’t reach statistical significance. So, you can confidently say to patients who ask about the side-effects of these treatments that they are incredibly well-tolerated and that the side effects are incredibly mild. In all of the studies the side effects leading to discontinuation was less than or around 1%. So, incredibly low. And a lot of people will be bringing their baggage of previous treatments with interferon to the consultation.
David: So, I have sort of gone over those details before. All genotypes for Epclusa and Maviret, genotype 1 for Harvoni, genotypes 1 and 4 for Zepatier and 12 weeks for all of them. So what are our options for Tim? He had genotype 1 remember? so you can’t go wrong, you can pick any of the medications on the PBS and Tim has the 99% chance of cure.
David: So what would you prescribe? Well, it doesn’t really matter, you could give him anything like I said.
David: But your eight-week regimens would include Harvoni because he had a low viral load or Maviret for eight weeks.
David: I mentioned drug-drug interactions. It’s probably not worth going into great details the drug-drug interactions except to say that they are sometimes very important and that there is a fantastic online resource. You may like to access it on your smartphone or you may prefer the laptop or desktop version. I prefer the desktop version because I can put in all patient’s concomitant medications, put in the suggested hepatitis C treatment. If there’s a drug-drug interaction that is incompatible the website will actually come up with an alternative, which is fantastic and then I can print out the PDF, put it in the patient's file, give a copy to the patient and the patient can even access the website and check any new medications that might come along. It is worth mentioning proton-pump inhibitors which reduce the absorption of some medications, statins sometimes are important and the dose may need to be reduced or the statin may need to be switched. There are no safe hepatitis C treatments with Tegretol, Tegretol carbamazepine changes your liver function, changes the enzymes and makes most of the hepatitis C medications disappear to such low levels that the treatment would not work. Ethinyl estradiol containing medications are important with Maviret and shouldn’t be used. St John’s Wort can have a similar effect to Tegretol. It is worth asking what else is the patient taking, and often taking often taking over-the-counter things that they may not remember or describe as medications. Nothing was relevant for Tim because he had no concomitant medications.
David: So, missed doses. I must say that with these new regimens they are fairly forgiving and you know one or two missed doses are not going to make a big difference. If someone's missing weeks at a time that will make a big difference and advice is obviously to try and sort of optimise adherence and to ask the patient to continue the treatment until it’s finished. If you are really worried about someone's adherence you may like to get them into your clinic more frequently just to check how many doses they have missed. Some people may even like to have the treatments to be dispensed with their opioid agonist therapy or by the pharmacy or by the clinic nurse. There may be lots of sort of novel ways of approaching difficult adherence. But remember that the regimens are relatively forgiving and as long as the person completes the course they should have a very high chance of cure.
David: Pill boxes, dosette boxes, mobile phone alarms, involving a significant other, and there will be other ways of optimising adherence.
David: You will notice on the PBS that treatment can be prescribed by any person experienced in the treatment of hepatitis C. Now, the number of patients needed to treat before you consider yourself experience is not defined. It’s really a level of comfort, some people may feel confident particularly with the pangenotypic regimens to feel experienced after just two or three prescriptions and that’s perfectly reasonable. Others may want a few more, you may treat 10 people and then come across something that you are not familiar with and seek further guidance. So, there are several ways of getting that further guidance, there are some remote consultation request forms, it can be downloaded from GESA or from ASHM or hepcguidelines.org or you may have a preferred specialist in your network or in your orbit who you are happy to contact. Personally I have my own sort of form or I am happy for text messages, emails, phone calls, it doesn’t really matter. There are many ways to give the appropriate advice and to sort of help you improve your level of confidence and share really the joy of treating people for hepatitis C, because even though we talk about all of the ins and outs and the detail it is almost always incredibly rewarding and incredibly successful.
David: So, who would we still prefer be referred for specialist care? Are those people with cirrhosis or whether suspicion of maybe early cirrhosis or advanced fibrosis? We didn’t talk about extrahepatic manifestations. Basically there we are talking about people, say with arthritis due to hepatitis C or a lupus-like syndrome or say renal disease related hepatitis C where you would still like to see them basically because they are uncommon and very interesting. Complex comorbidities are someone with say severe cardiac disease, severe renal disease, HIV or hepatitis B dual infection. I mentioned earlier someone who has failed their first attempt at DAAs as a treatment failure no longer naïve to therapy, where you would prefer to see them? In specialist care, because their second treatment may be difficult. People with acute hepatitis C, remember the PBS is just for chronic hepatitis C. So, someone with acute hepatitis C isn’t actually eligible under the PBS.
David: We would find ways to consider treating their acute hepatitis C and that may actually be in a clinical study. Many of the tertiary centres and clinics around the country have access to clinical trials of acute hepatitis C where we are exploring shorter durations of currently available therapies.
David: So, monitoring and followup. So, we have mentioned the things to do at baseline, we have put there a viral load, although as I said earlier that is really an option rather than necessary. We have put in light grey LFTs on week 8 of Zepatier. It is in the product information, it’s something that we should do, it’s something that’s often not done with no particular consequence I must say. I said in some people we would test at the end of treatment. I would only do that if I was really worried about adherence or in someone with decompensated cirrhosis. For the vast majority of people, actually the only blood test they need is a test three months after they finish treatment, so post treatment week 12, where we are testing for cure. We are doing a hepatitis C PCR for (audio distortion) a yes or no test, a qualitative test. We are also doing some liver function to see if that has returned to normal if it was abnormal at baseline, and we do note this cure of hepatitis C or sustained virological response 12 weeks after treatment. So, as you know everything in medicine has a convoluted acronym and this is the convoluted acronym in hepatitis C, the SVR12. We have mentioned there in the fine print ribavirin. We are really not talking about treating people with ribavirin anymore except in sort of complicated re-treatment scenarios and I mention people with cirrhosis who might need closer attention.
David: So, we chose to give Tim just 8 weeks of sofosbuvir/ledipasvir or Harvoni. He was busy working so he didn’t come in the week for, we just telephoned him, he was doing well, slight headache which may have had nothing to do with his Harvoni. We thought about some Panadol and didn’t take it. He hadn’t missed any doses, which is great, and then we did a blood test 12 weeks after he finished treatment. His liver tests were normal and his hep C RNA was negative by PCR. So, he achieved the SVR12. So, is he cured? Does he need any further followup? Ten years ago we were sort of hesitant to use the word cure. We now have no hesitation in saying that Tim is cured of chronic hepatitis C. He doesn’t have to tell anyone he has got hepatitis C, he does not have hepatitis C anymore, it’s in his past history column, he is cured of hepatitis C. Does he need any further followup? Well, he is not at risk of reinfection because his last exposure was almost 40 years ago and he doesn’t have cirrhosis.
David: So, as I am comfortable as it feels for a chronic medical condition he actually doesn’t need any further followup. You know, the door is always open for some future problem to re-present, but we should be telling people like Tim that he is cured of hepatitis C, he doesn’t need to keep testing for it, he doesn’t need to worry about it, he doesn’t need to tell anyone about it. The only thing he couldn’t do really is donate blood or join the Army. Remember that hepatitis C antibody tests remain positive after cure. That will remain positive indefinitely, so 10 years, 20 years, a lifetime and it should not be repeated. We often see that it is repeated say Tim moves workplaces again and goes to a new GP. He may mention the hepatitis C and the new GP may do an antibody test. Tim may have forgotten about this treatment in 10 years’ time because it was so innocuous and the positive antibody may sort of trigger his memory of this treatment.
David: Treatment failure. So, if you treat a 100 patients, one of them will experience a treatment failure. That’s where there is still virus detectable by PCR 12 weeks after treatment completion. So, that’s where we would like to see them in a tertiary centre because that’s a treatment failure and the second treatment is going to be a little bit more complicated, which again is the topic of another webinar.
Do we have one more polling question?
Amy: We do.
David: There we go. So, your patient achieves SVR12, has no cirrhosis, but is at risk of re-infection. What post-treatment followup would you put in place? So, monthly antibody, an annual PCR, six-monthly antibody and PCR or an annual antibody… to be distinguished from the monthly antibody. So, we just said earlier that the antibody is going to stay positive for decades. I think I have seen maybe three antibody clearances in my almost 20-year career, so it’s pretty infrequent and most of you have answered, so that’s good and most of you have said correctly the hepatitis C PCR. So, in someone at risk of reinfection Medicare will let us do a hepatitis C PCR once a year to look for reinfection. Now, if six months later the LFTs are abnormal again, that would be the time to do it rather than to wait another six months so that a year has elapsed. And what you would write in your clinical notes on the request slip is just ? acute hepatitis C reinfection and the laboratory could then do the PCR under Medicare. So, who needs followup? People without cirrhosis don’t need followup. People without risk of reinfection don’t need followup. Men having sex with men or men with HIV or people injecting drugs should have ongoing annual PCRs. Now, if the liver tests don’t completely return to normal then we may need to think of other causes for abnormal LFTs and that’s why you should think about referring them to a gastroenterologist and it may be something as simple as fatty liver disease, which as you all probably know affected a third of adults, but it’s worth thinking about other causes including autoimmune conditions or haemochromatosis or other blood-borne viruses if the testing for that wasn’t performed and it’s worth considering referral. But Tim as we said, does not need any further followup.
David: I don’t think it is of worth going into great deal about what happens to people with cirrhosis, because remember they are the ones that you are referring to specialist care anyway. So, this gives us something to do because from specialist care we are seeking the help of all GPs in the country and giving away all of the easy people without cirrhosis to treat, so you have got to leave us something to do in the specialist care ivory tower. So we are performing surveillance for hepatitis C and carcinoma with six-monthly ultrasounds. We are vaccinating for other infections. We are looking for decompensation and doing screening and surveillance for varices and osteoporosis. So, that will keep us busy for decades to come.
David: I mentioned surveillance for HCC, basically we are doing ultrasounds and we are doing alpha-fetoproteins with the caveat that it’s not a very good test.
David: So, other special issues you may need to think about. So, people with prior treatment I mentioned, pregnant women, we can’t at the moment recommend treatment with DAAs. If they are pregnant we would wait until delivery. Treatment failure, we are going to see them in specialist care.
David: I mentioned the general statement for the drugs of treatment for hepatitis C via the PBS website that you follow, put in one of the drugs into search, like sofosbuvir, follow the clicks and you will end up at the general statement, or you can go to the consensus statement which was put together by GESA, ASID, and Hepatitis Australia, ASHM and others and ____.
David: So, I think this is our last polling question and then we have got 10 minutes for your questions. So, Jemma is wanting to have a child, she has got medium fibrosis or moderate fibrosis, genotype 1. What would you suggest? Start treatment now and she can wait six months after treatment before conceiving. Start treatment now and wait a month. Conceive now, there’s only a 1 to 2% chance of transmitting to her baby, or conceive now, start treatment after delivery because there is no risk in breastfeeding. So, this is a little bit complicated and just saw that you’ve got plenty of time to ask your other questions, I might just close the poll early.
David: It’s a tricky one because I didn’t really sort of tell you much of the answers. Those of you who’ve said six months, that you need to wait six months after treatment, that was true for interferon and ribavirin, but in fact with these drugs we think you only need to wait for a month. So, look you could argue the toss on those, but we would only suggest waiting a month and then Jemma should be able to conceive. That 1 to 2% risk of transmission is a little low, I mentioned earlier it was 3 to 5%. We don’t know much about any of these medications in breastfeeding women. So, the advice in all of the product information is that only do it if benefit outweighs risk.
David: I think that might be one more…okay. Ah yes. So, when a DAA is contraindicated. Well, in pregnancy we still, you know the category B, which is not A I guess, but that is still contraindicated in pregnancy, we don’t use ribavirin anymore, ribavirin was teratogenic category X. We would suggest avoiding during lactation. We recommend contraception during pregnancy and we suggest waiting 4 weeks like I said.
David: I have mentioned treatment failure is very uncommon, 1%, and we want to treat those people in specialist care. I mentioned earlier that reinfection is not a treatment failure and we are quite happy for GPs to treat reinfection. You treat that new infection as if it were a first infection and you may even need to use the same regimen again as long as you are confident that it’s a reinfection, and you would be confident if it were a reinfection if they have had that negative test 12 weeks after treatment finished that SVR12 time point.
David: So, I think we have got there.
David: Yep. So, you can see the websites there for further learning, but I might go back to Amy. Amy, have you had any questions from our attendees that you thought we haven’t addressed?
Amy: Yes. Absolutely, and thank you very much for that presentation David. There were quite a few people asking about vaccinating against hepatitis A and hepatitis B for people who are either hep C positive or about to start or undergoing treatment and what were your thoughts there?
David: A very good question. There should be no interaction between the vaccine and hepatitis C treatment. So, I would do the two to get …. I wouldn’t wait for vaccination before you treat and I wouldn’t wait for treatment before you vaccinate. So, I mean, many of our attendees may be in areas where there has been a recent hepatitis A outbreak, and so there have been programmes to sort of catch up or treat people who might be at risk of hepatitis A with the vaccine. Hepatitis B vaccine should be available free to anyone with hepatitis C. There are various reasons for hepatitis B vaccination to be available free on the PBS and, having hepatitis C, I don’t think it’s specified, but there’s a sort of a broad indication which is anyone at risk of hepatitis B, and so you can argue that having hepatitis C means that getting hepatitis B puts you at greater risk or you might have hepatitis C because you’ve been injecting drugs and therefore, are at greater risk of hepatitis B. So, it’s one of those indications for the free access to the vaccine. So, hepatitis B is three vaccines over six months at 0, 1 and 6 months and then you do a blood test to check surface antibody levels one month after the third injection. Hepatitis A vaccine can be done as a Twinrix vaccine with the hep B or it can be done separately just as one vaccine, which gives you a year or two’s immunity or two vaccines a year apart which gives you 10 years’ immunity.
Amy: Excellent. And just one final question again, we had quite a lot of interest in the beginning relating to transposition through sex, whether it is in fact a sexually transmitted infection or what types of sex causes transmission of hepatitis C.
David: Very good question. So, we over the last 30-odd years have said….. no, that’s too long…. 28 years…have said that hepatitis C was not a sexually transmitted infection and the reason for that was that transmission in stable heterosexual couples was incredibly uncommon at around 1%. That message that it’s not a sexually transmitted infection needs some caveats, and those caveats are people with multiple sexual partners. People at risk of other sexually transmitted infections, particularly syphilis, we see a lot of co-transmission of syphilis and hepatitis C. We also see a lot of sexual transmission of hepatitis C in men having sex with men. And the reasons for that are complex, but it probably reflects more risk of mucosal breach. So, normal vaginal mucosa without a tear and without bleeding should be relatively resistant to hepatitis C and that’s reflected in the lack of transmission in heterosexual couples. But other mucosa such as anal mucosa, rectal mucosa or the use of drugs while having sex or multiple sexual partners while having sex, they may mean that hepatitis C is sexually transmitted, so that’s where that sort of broad statement needs some detail, and look, there may be attendees who are highly experienced in the area of sexual transmitted infections or much better at taking a sexual history than I am, but I think just broadly it’s not transmitted between stable heterosexual couples but it is transmitted in more high risk situations would be a reasonable summary.
Amy: Excellent. Thank you very much David, I think we will stop there. There were lots of questions, you actually managed to answer a lot of them during the course of the presentation, but there is the potential that we might collect some of those questions and send out some answers later in the email. Just a reminder to participants, you will receive a post of an email and you need to complete the survey to get your CPD points and you can add your RACGP number there if you haven’t already. There was a question about whether the slides would be available. We will need to confirm that with ASHM, but if we can send them to you that will be included in that post event email. So, I would like to again thank you Dr David Iser for what a fantastic and informative presentation.
David: Thanks Amy.