SAMMY: All right good evening everybody. It is now 7:30 so in the interest of time we will make a start, so welcome to this evening’s Curing Hepatitis C in General Practice webinar. This is another instalment in the Twilight Online series. Our facilitator for tonight is Dr Marie Healy and our presenter is Dr Joseph Lawler. Before we get started I would just like to make a quick acknowledgement of country. We recognise the traditional custodians of the land and sea on which we live and work.
Just a bit of background on our presenters this evening. Dr Joseph Lawler was awarded his medical degree from the University of Sydney in 2004. He completed his advanced training in gastroenterology in 2011 having trained at RPAH and Liverpool Hospital in Sydney. He completed a clinical fellowship in liver medicine and liver transplant medicine at Mount Sinai Hospital in New York City in 2014. He is now consultant gastroenterologist and hepatologist in Sydney, south-western Sydney and Western New South Wales LHD.
Dr Marie Healy has been a GP in Redfern for more than 20 years with experience and interests in aboriginal health and aged and chronic and Marie has been a RACGP examiner for 15 years. I am going to hand over to Marie now and she will take you through the learning outcomes for this evening and then we will jump into the presentation.
MARIE: Good evening everyone. This is Marie. What we are hoping that you will get out of this webinar is firstly to identify the priority populations for hepatitis C testing, interpret the test results and diagnose hepatitis C accurately. Hopefully you will be confident about doing that at the end, assess for liver fibrosis complications and comorbidities and initiate treatment monitoring and follow-up according to the Australian recommendations for the management of hepatitis C virus infection, a consensus statement 2017 and you will find that consensus statement, you can access that, at the end there are some references there. You can do that.
JOSEPH: It is Joe here. I was going to talk to the issues around epidemiology and hepatitis C in Australia. In Australia the estimated prevalence of hepatitis C is about 230,000 and you can see in the graphic there that most of the hepatitis C in Australia is genotype 1 and the second most common genotype is genotype 3 with the remaining genotypes making up that small proportion. There are about only 15% of people in Australia that have hepatitis C that are not yet diagnosed. So our diagnosis rates are pretty good. Just to remind you that there are six main genotypes of hepatitis C but in the era of Epclusa which we will come up against later, the role of genotype in terms of choosing your treatment regimen is becoming less relevant with these pangenotypic medications. Another thing to remember in Australia is that there are some populations and subpopulations in Australia that have more common rarer genotypes, like the Egyptian population in Australia is commonly infected with genotype 4. So that is something to keep in mind.
Now in terms of the natural history of hepatitis C infection remember that a quarter to up to a third of people can clear the virus spontaneously. So what we are talking about today is about chronic hepatitis C. And of a 100 people that develop chronic hepatitis C you are not going to see problems with their liver for 20 to 40 years. Of the 100 people that would be infected with chronic hepatitis C, 45 of those are not going to develop serious liver damage. About 31 might develop mild-to-moderate liver damage that might be only able to be discovered on testing and 20 of those 100 people might develop cirrhosis, the one of the more few complications of hepatitis C and again a smaller number might develop decompensated cirrhosis or liver failure or liver cancer.
So in terms of the benefits of curing hepatitis C I think it's important to think about it in two different ways. One is from a public health perspective and one is from an individual's perspective. So on this slide you can see that there is a mission there to reduce the transmission and hopefully eradicate hepatitis C in Australia because of our most generous Access program. Now in terms of the individual outcomes, in non-cirrhotic patients the goal is to reduce the risk of an individual's progression to cirrhosis and liver cancer and improve their overall survival, not just from liver disease but from all-cause mortality. In cirrhotic patients we are looking to reduce the rates of clinical decompensation and variceal bleeding for example, ascites and encephalopathy. We can also see regression of decompensated liver disease with eradication of hepatitis C, not always but sometimes and the aim is to improve liver-related survival. In getting those decompensated patients in the population it is jaundice, with ascites and encephalopathy and variceal bleeding we are looking at a reduction of the rate of decompensation, progression of the liver disease, reduce the need for liver transplantation and also manage the significant risk of hepatitis C recurrence post liver transplant and improve transplant outcomes. As I mentioned before there are some other reasons that we like to treat hepatitis C from an individual level. We see improved quality of life. We see improved neurocognitive function and energy levels. We see improvements in renal disease particularly in hepatitis C related diseases, as a complication of cryoglobulinemia. We see reduced risks of malignancy and also see improvements in the metabolic syndrome.
MARIE: So the other benefit Joe is to reduce transmission and to really push against hepatitis C existing in Australia.
JOSEPH: Yes that is right. With open access we can target and treatment of every person with chronic hepatitis C where the aim is not only to eradicate it from an individual but reduce the transmission within its high-risk populations.
MARIE: Yes and intravenous drug users.
JOSEPH: No it is not independent. We know the indigenous population do suffer poorer health. We know that the incarceration rates are higher and so there are greater opportunities to be exposed to the risk of transmission so indigenous status itself alone does not increase the risk but it is a priority population because of the social determinants of health and exposure to other risk factors. So we do need to explore, it is not just that it is people of indigenous ethnicity, it is about the risk factors. It is a bit of a priority population we can see that reflected in the notification rates.
MARIE: And what about men having sex with men?
JOSEPH: Yes it is a really important point. It does, when we talk about the sexual transmission of hepatitis C being low that is with penetrative vaginal sexual intercourse. With anal sex there is increased trauma and an increased risk of blood supply exposure and it is all about that blood supply exposure.
JOSEPH: So that is another important population to keep in mind.
MARIE: Okay. We have talked the testing now. When hepatitis C is confirmed it is important to have an action plan and provide support and advice so it is really important that GPs can offer to the patient ways to improve their liver and their general health. One of the first things is providing support for those people. There are going to be issues with stigma and discrimination even, that they may have actually delayed having the tests done and then seeking treatment. So providing access and links to information and peer support groups, discussing legal issues, sexual disclosure will important. I guess if you are going to be hopefully getting involved in treatment it would be great to set up and to find out what sort of local groups are available in the area that you are working. Discussing lifestyle factors with drug use, smoking, alcohol, hepatotoxic medications, maintaining a healthy diet, exercise, lose weight if necessary, medical issues, talking about specific treatment options, referrals, immunisation and monitoring and preventing transmission through social behaviour, counselling and things like sharing needles, using clean syringes, needle exchange programs, harm reduction, needle and syringe program, opioid substitution therapy and those things are really important.
In terms of the pre-treatment assessment, we are going to talk about how you go about assessing a patient before you are going to engage them in treatment. Firstly it is important that you do further blood tests and so there is a PBS requirement that you know the genotype and the subtype and also the viral load for genotype 1. There is a shorter course of treatment available there so a quantitative HCV, PCR as Joe mentioned.
JOSEPH: I will just jump in there too. There is a PBS authorised regimen of eight weeks for people with genotype 1 in hepatitis C without cirrhosis that have a viral load of less than 6 million.
JOSEPH: That is the specific thing there.
MARIE: That is the importance there. Now assessing the degree of fibrosis is very important because it is, we want to know the likelihood of advanced liver disease or cirrhosis. There is a PBS requirement but it is also important in terms of prognosis, the urgency for treatment, the need for pre-treatment screening of varices, or for hepatocellular carcinoma
JOSEPH: And the prompt referral to specialist care as well.
MARIE: Yes exactly. The duration of anti-viral treatment well I suppose you know
JOSEPH: It used to be important but now we have got the pangenotypic regimen, there is only one duration of therapy being 12 weeks.
MARIE: Right okay.
JOSEPH: With or without cirrhosis so again as the treatment evolved, the recommendations have changed there.
MARIE: Okay we would also assess for other factors that might influence the disease progression such as prior treatment experience. Now they would need to see a specialist if they had failed treatment and co factors such as alcohol use, metabolic risk factors, hepatitis B or HIV co-infection now some of those people would need obviously to be seen by specialists as well. So other tests that you do in the work up of patients before they are treated is a full blood count, liver function tests, UEC, estimated GFR, INR and AFP and you are looking there, well you are looking at their renal function that is important from a pharmacological point of view, but the other things are looking at are other markers for cirrhosis and liver dysfunction which we will talk to in a later slide.
JOSEPH: I will just raise the point about the baseline renal function as well. That is a really important differentiator as to whether a patient can be treated in general practice or in a specialist context. All of these treatment regimens require a GFR of greater than 30 so that is again, cirrhosis detection is important in that community workup. The evaluation of renal function is important.
MARIE: Okay great. Now we need to check the hepatitis B virus, hepatitis A, and HIV. This is for a couple of reasons to work out whether you need to vaccinate them but you can also have a problem, the treatment can cause a reactivation of hepatitis B. Is that correct?
JOSEPH: Yes so that is one of the reasons why I think a co-infection needs to be managed in a specialist setting and also one of the other role of doing hepatitis B and hepatitis A serology is to vaccinate in somebody that is susceptible so they do not acquire a second hepatitis infection. That can be quite catastrophic in somebody with existing liver disease.
MARIE: Yes exactly. A pregnancy test done, also asking about childbearing wishes and potential liver ultrasound if cirrhosis is both considered and an ECG would be in patients with cardiac risk factors and over 50, ribavirin but that will be in a specialty setting.
JOSEPH: Specialty setting yes. Okay a question has come through asking whether every patient needs a Fibroscan before treatment and the answer is no. There are other assessments for fibrosis that we use and we will go through those a bit more later but you can use the AST to platelet ratio index to evaluate for cirrhosis risk and also look at your investigations more holistically including your assessment of platelets and INR and your imaging findings as well. So Elastography or Fibroscan is not essential to treat.
MARIE: Okay. Now there was a question there too I was told could only do a HCV, RNA once every 12 months. I think you are saying that is not. If you are planning treatment you can
JOSEPH: To diagnose chronic hepatitis C you need the two readings separated by at least six months.
MARIE: Yes, okay, good. So we will go on to talk about Fibroscan I think now, will not we.
JOSEPH: Yes some of you might be familiar with Fibroscan. Fibroscan is one of the machines that are available and it is transient elastography. So a probe is placed at the bedside over the liver on the right side between the intercostal spaces and sound waves are transmitted through the liver and reflected back to the probe and a calculation is made on the basis of the velocity of that wave to work out how stiff the underlying liver is. Now this test is not infallible. It is very good for saying that the liver is normal and it is very good for saying that the liver is cirrhotic but it is not so great at working out those indeterminate levels of fibrosis and so that is why we use other markers and other assessments to look at someone’s risk of having cirrhosis. I mentioned, as it comes up on the next slide, the APRI which is a simple calculation that you can download as an app or just Google it and you will find a calculator online and all you need to know is the platelet count, the AST, the upper limit of normal of the AST and plug that into the calculator and you will get a risk score.
MARIE: Do you know Joe if the Fibroscan is Medicare rebatable?
JOSEPH: No it is not. No.
MARIE: They are usually done at the hospitals are not they and the patient will not have to pay then?
JOSEPH: That is correct and it is usually done as part of the liver clinic and I think different joint health services have access and that access is being provided by New South Wales Health and those machines are distributed throughout the state. So yes there is access there but you will need to approach your nearest liver clinic but as I said like you can assess for fibrosis using the APRI which is a combination of commonly ordered tests including the AST and the platelet counts. We use a cut-off of 1.0. Any number that comes through as greater than 1 does need a closer look for cirrhosis but less than 1 you are pretty confident that cirrhosis is not there but remember that you are using all of your other assessments to make that call.
MARIE: Okay so we have talked about the Fibroscan and the APRI but why are we assessing for cirrhosis? We are really doing it for prognostic reasons and to work out how urgently somebody might need treatment and generally people who do have cirrhosis will need to be under specialist care. It is also really important to know that these people would need a pretreatment assessment for varices, hepatocellular carcinoma and it is also working out the duration and the type of treatment that they will have. It is a PBS requirement as we previously said to state whether the patient is cirrhotic or non-cirrhotic and people with cirrhosis will have specific follow-up arrangement. We will talk about assessing cirrhosis because it is not actually a single test so we might go onto this slide. It is really, you need to do a holistic assessment of a patient. So the first thing is a history and examination and, so the history would be have they had any symptoms that might indicate cirrhosis, have they had oedema, especially central oedema or some peripheral oedema, any easy bruising, any episodes of jaundice and those sorts of things and then on examination they will look for signs of cirrhosis including maybe a small nodular firm liver, signs of portal hypertension, well that would be you know you will find there might be some ascites,
JOSEPH: Yes yes, prominent abdominal wall veins.
MARIE: Yes, yes, you know
MARIE: Yes, what about lots of spider nevi on the chest.
JOSEPH: Well it does not indicate portal, and I will correct myself, jaundice is not a sign of portal hypertension it is just a sign of decompensated liver disease, that was my mistake but spider nevi are associated with decompensated cirrhosis.
MARIE: Yes, so then blood testing, liver function tests, albumin, which could be low, platelet count low because of the splenomegaly and coagulation profile, serum markers, we have talked about the APRI, the HEPA scores. Somebody asked about the HEPA score.
JOSEPH: I think it is harder to get and more expensive and I think just utilising the readily available test and commonly ordered test and plugging those into the free online calculators is I think the way to go.
MARIE: The Fibroscan, and ultrasound, I guess if you do not have access to a Fibroscan and you wanted to really check out whether there were signs of portal hypertension I think
JOSEPH: Micronodular cirrhosis, macronodular cirrhosis, a dilated portal vein, splenomegaly, all of those things, an ultrasound can be very helpful.
MARIE: Now liver biopsies are not done?
JOSEPH: No, no and it used to be a PBS requirement for hepatitis C therapy but that is no longer the case so liver biopsies are not required to treat hepatitis C in this age.
MARIE: Yes, as you can see, look it is an overall assessment that will give you an idea of whether this person likely has cirrhosis and if you feel that they do, management with a specialist would be the way to go. If this person does have cirrhosis, they will need special monitoring and that will be a shared care arrangement with a specialised clinic in most cases so they do need a hepatocellular carcinoma screening because they are at an increased risk and that would be usually done with an abdominal ultrasound plus an alpha-fetoprotein level
JOSEPH: Every six months in a cirrhotic patient.
MARIE: Every six months, yes okay. I do not think that is often done
JOSEPH: No it is very hard to achieve. Very hard to achieve.
MARIE: Yes, yes and I hope people take it up. Variceal screening, repeating gastroscopy at two to three yearly intervals if no varices initially. Screening for hepatitis A and hepatitis B and offering vaccination if required. Hopefully you have done that in the previous workup of the patient, annual flu vaccine, and I would add the pneumococcal vaccine as well and screening alcohol use and talking about hepatotoxins.
JOSEPH: And sort of an important point too, with cirrhosis there is no safe amount of alcohol to be drinking and ideally for people with cirrhosis, abstinence would be the goal.
MARIE: Yes, yes. Alright, that is great.
JOSEPH: One of the issues that comes up in this age of DAA therapy for hepatitis C is the risk of drug-drug interactions. It does sound pretty daunting but there is a pretty easy way around it. Resources that you really must be familiar with and it is readily available online is the Liverpool University drug interaction website and the details are not really coming up on the slide there so hopefully will come up in a later iteration of these slides, oh there you go, so very easy to find and very easy to use. All you need to do is plug in the treatment regimen that you want to use and then list all of the medications that the patient is on and then the significant interactions will come up. There are sort of some drugs to keep an eye out for. Co-administration with statins is generally contraindicated with these classes of drugs because it increases your risk of statin-induced myopathy. Co-administration with the stronger proton pump inhibitors like pantoprazole, esomeprazole, can reduce absorption of the medication and cause the SVR rates or the cure rates to drop off if there is co-administration. Some of the anti-epileptic drugs particularly carbamazepine can increase the metabolism of the drugs and again affect cure rates and only with some of the combinations and preparations like the AVRI product, you need to be careful with the birth control that you are recommending. St John’s wort pops up as well.
MARIE: It pops up with everything.
JOSEPH: It pops up with everything. And it is really important to be aware of people’s use of those over-the-counter medications as well as prescription medications.
MARIE: What about alcohol, somebody has asked.
JOSEPH: Yeah I saw that question come up and absolutely there is no contraindication to treating people that have chronic hepatitis C and alcohol.
MARIE: Oh really?
JOSEPH: Yes, again it is very different to the interferon over the years when treatment really knocked people around and if there was concurrent alcohol dependence that might have been a red flag to not proceed with therapy but thinking about the ease at which hepatitis C can eradicated you can actually reduce one of the risks of the progressive liver disease. Anyhow, I am not saying ignore their alcohol, treat that but it is certainly not a contraindication to treat. There was just one other drug that is not listed that I think we need to remember and that is amiodarone.
JOSEPH: There has been some evidence of profound bradycardia in patients that have co-administration with amiodarone so that is definitely an absolute contraindication to co-administration as well.
MARIE: Okay well that is good to know.
JOSEPH: And remember that the treatment course is on average pretty much 12 weeks, people can be prescribed other medications by other providers so reminding patients to let you know as the treating hepatitis C treatment doctor that you need to be told if any other new drugs are being prescribed so you can check for interactions.
MARIE: What is the ideal birth control sort of preparation, I have double protection
JOSEPH: Double protection with ribavirin,
MARIE: Oh I see.
JOSEPH: Again and that needs to continue for six months out from therapy, so that is a good question.
JOSEPH: So going on to the next slide. This is an example of how the interactions will come up. So you have got the absolutely do not go there, demonstrated with the red circles, and the green diamonds gives you the all clear and then the amber square is not an absolute contraindication but maybe something to watch.
MARIE: So amiodarone is not listed there is it? So it should, that would be a good
JOSEPH: Look this is just a sample. This is not an all inclusive list.
JOSEPH: And again it is just an illustration of how the website does appear.
JOSEPH: Alright so going on to the next slide, now with ribavirin free regimens, they are pregnancy category B, so pregnancy is a contraindication to treatment and as we were just saying, we recommend contraception during therapy and that point there of not using oestradiol in the regimen which is not often used in this age.
JOSEPH: Again if you are concerned, just return back to the Liverpool drug interaction site.
JOSEPH: Now ribavirin is not really going to be used in the community setting but just remember that it is teratogenic and it is category X in pregnancy so as we were just talking about two contraceptive methods are required for up to 6 months after therapy completion because of the long half life of ribavirin.
MARIE: Now there is a question about Panadol and Panadol Osteo use. So if you are under treatment for hepatitis C use of Panadol is not contraindicated?
MARIE: I think people are more thinking about people with cirrhosis which has
JOSEPH: Yes in cirrhosis you can generally use half the recommended dose of paracetamol, so it is no more than 2 g a day.
MARIE: Okay. Great.
JOSEPH: So moving on to the next slide.
MARIE: Okay. Well we were talking about treatment in primary care or referring. So in terms of who should you consider for treatment for hepatitis C and the answer is anybody who has chronic hepatitis C. Those with limited life expectancy due to non-liver or non-HCV-related comorbidities would be the only group that you will not treat but those who are very unwell with HCV-related conditions would be seen by a specialist anyway so all people living with hepatitis C virus should be considered for treatment. There are no liver disease stage restrictions on the PBS, so all people can access treatment but you must know whether they have cirrhosis or not for PBS requirement. It is just that the people with cirrhosis will be seen by a specialist and it is important that you provide the patient with adequate information to make decisions on treatment. So we did talk about how you work up a patient and how you support them once they have the diagnosis and then you discuss obviously what side effects the treatment could have and the interactions and work out their pregnancy status, so when to consult with, or refer patients to a specialist? So for the first, anybody with hepatitis C who you are going to treat, are your first 10 patients that you will be treating with a specialist anyway but the people that you would want to consider sending to a specialist would be those with advanced fibrosis or cirrhosis or those with extrahepatic manifestations.
JOSEPH: Like the cryoglobulinemic vasculitis and glomerulonephritis, things like that.
MARIE: Okay. Patients with complex comorbidities, they might have diabetes that is not well controlled or other conditions. Patients with renal impairment
JOSEPH: And using that GFR is 30.
MARIE: Yes, 30 as the cut-off, yes. Patients with HIV, a co-infection or a hepatitis B co-infection because you can have a reactivation of hepatitis B and HIV obviously will have a greater risk of drug interaction.
JOSEPH: Drug interaction, yes a specialist setting would be recommended.
JOSEPH: And those groups are also at greater risk of progressive liver disease as well.
MARIE: Patients who have failed first line therapy they will need, I guess a longer course too but that is second time around or?
JOSEPH: We do not have salvage therapies available on PBS at the moment but they are coming.
JOSEPH: But they are as good, they are as good. The details of those are coming through at the moment.
MARIE: Patients for potential clinical trials and those with acute hepatitis C because we are talking here about treating chronic hepatitis C so they have had the RNA for six months. So they are the ones we are that talking about treating in general practice land. So we will go on to treatment and monitoring then, so as I said there is a consensus statement that you can access through the references at the end but in terms of hepatitis C treatment you need to be aware of the current PBS listed treatments and management recommendations and here are two resources for you. Look, you should always look up the PBS one because they will change and things are evolving very quickly are not they Joe?
MARIE: So as Joe said there is pan
JOSEPH: Pangenotypic regimens
MARIE: I cannot say that word. Pangenotypic. Anyway there is one that will cover a whole lot of viruses and these are the ones that are coming out so. Choosing the most appropriate hepatitis C regimen for treatment. So there are something that you need to consider and these are partly you know you need to think about how you are going to approach this person but also for PBS requirement so their genotype and their subtype in some cases
JOSEPH: Again that is probably in the earlier treatments but in the most recent wave of treatment with Epclusa that is not important.
MARIE: Yes. So the presence or absence of cirrhosis, both so you, the PBS requirement is also for referral purposes. Whether they have had prior treatment experience because then you would need to refer them. Co-morbidities. Drug interactions, so what medications they are on and the potential resistance. So across all of them cure rates are greater than 95% which is fantastic and for all of them you can use the pangenotypic treatment regimen and it is effective across all the genotypes. So is that available now?
JOSEPH: Yes. It has been available since 1 August.
MARIE: Okay. All right. Look I guess the thing is the treatments are getting simpler and simpler. These drugs are well tolerated and monitoring is quite simple so we will go into that fairly soon.
JOSEPH: So going onto that next slide which illustrates some of the treatment options that are available on the PBS and these are currently listed on the PBS but it illustrates how the treatments have evolved from when we had our first PBS listing on 1 March last year through to the most recent listing of Epclusa, sofosbuvir, velpatasvir listing on 1 August of this year. So looking at this complex slide I really want to drive home, a really simple point that that bottom row there with the sofosbuvir, velpatasvir, forget about the ribavirin because that is going to be in the context of cirrhosis and in specialist care but in the community you can use that one drug for 12 weeks for genotypes 1, 2, 3, 4, 5 and 6. There are no other treatment considerations. So that is one of the take-home messages from this slide. Again I will just make the point that if people are thinking about using ribavirin that is generally in the context of specialist care so that keeps it all nice and simple.
MARIE: Somebody has asked if a male partner is being treated is there any issue with them making their partner pregnant. Is there any sort of carriage of the medications?
JOSEPH: With ribavirin yes.
MARIE: Right yes.
JOSEPH: So contraception is recommended with ribavirin but not with the DAA.
MARIE: Okay. So the PBS requirements. We will just look at now.
JOSEPH: I think there is one more slide before that. And it just talks to the point of the tolerability of these medications, so we have already seen from what Marie said, the cure rates are greater than 95% for most of these patients you will be seeing in general practice and not only that the side effects are pretty minimum so if you are the 1% of people who have to stop the medications because of side effects. In general terms, nausea, headache and fatigue are commonly seen, a bit of diarrhoea and with the latest combinations nasopharyngitis which I have not seen yet but that has been reported in the literature. Then just in that little box on the side there you can see there is another subset of side effects in ribavirin-containing regimens and that is just not really relevant for prescribers in the community but also probably relevant to the patients that have been treated within a specialist centre. So being aware that ribavirin is associated with haemolytic anaemia and decrease in the haemoglobin can be associated with insomnia, nausea, and also affects concentration.
MARIE: Well it is really great that they are so well tolerated, the new ones though is not it.
MARIE: So let us look at the PBS requirements. Now the people do need to be over 18 and they must be treated by a medical practitioner or authorised nurse practitioner experienced in the treatment of chronic hepatitis C infection. We will talk to that. The information that must be provided on the application, the hepatitis C genotype and the patient’s cirrhotic or non-cirrhotic status and in their medical record you must have documented evidence of chronic hepatitis C infection and the hepatitis C genotype. This is contained in the general statement for drugs for the treatment of hepatitis C. If we go to the next slide I did say that somebody experienced or a clinician experienced and that is where you gained experience of treating at least 10 people in conjunction with a consultant and basically
JOSEPH: Infectious disease is already gastroenterologist.
MARIE: Yes. So you really, and we will talk there is a form you can use and really you know if you can just engage with a specialty service or a consultant and complete 10 treatment courses then you will be an experienced prescriber for the purposes of the PBS.
JOSEPH: While we are waiting for the next slide a question has come up asking whether abstinence from ongoing IVDU is required to access treatment and again the answer is no. So it is a similar answer to the question about alcohol use and it goes back to that idea of the population approach to eradicating hepatitis C in Australia and we are really aiming to treat this population, reduce the viremia in that population and reduce the risk of transmission.
MARIE: And I guess somebody who is actively using is maybe more of a risk of transmitting the virus to others.
MARIE: So it is an even better reason to treat than not is it not.
JOSEPH: But of course the caveat to that statement is that often people that are injecting are very chaotic and they might not even be able to comply with one pill once a day for 12 weeks and the monitoring so I think you know when you think about the compliance perspective that might affect your decision to treat but as an absolute rule ongoing injecting drug use is not a contraindication to treatment.
MARIE: Okay so here is your PBS listing authority and dispensing guide so it is prescribed under S85 in the community and basically you would be starting off with the fourth one down. You would be an other registered medical practitioner following consultation with an HCV treatment experienced specialist is so your first 10 courses at least would be under the guise and then you would move up to become the medical practitioner or authorised nurse practitioner experienced in the treatment of hepatitis C infections. So that is how you would be prescribing there. The others are really done by specialists either in the community or in hospitals, in prison. So they are the ones that apply to the GPs. On the next slide there is a form that you can use and you can download it from the GESA website and this will give you a place where you can put all the patient details, I guess the genotype and your results and whether they have got
JOSEPH: Any fibrosis assessment and all that sort of stuff. It is not essential. It is just a guide. The PBS has got quite a liberal interpretation of what consultation means. A consultation could mean a corridor conversation with the specialist, it could mean a telephone call, and email, fax, this is just a suggestion in a format that is quite easily accessible through the GESA website and most have been adapted for liver clinics around the state and if you contact your local liver clinic to find the details, some of you could send that to sign off on your treatment choice.
MARIE: And I guess it ticks the boxes that you have gone through the assessment and maintain the criteria
JOSEPH: Absolutely and it gives you more comfort in your decision-making process.
JOSEPH: It really walks through all the things you need to consider.
MARIE: Okay. That is great. So then you can ring up your favourite number and you will be asked. The number of weeks for treatments. Now it is usually going to be 12 but you did say there is an eight week treatment for
JOSEPH: Yes for high boning, for the genotypes 1 with less than 6 million copies.
MARIE: Okay. Yes. They have made the general statement. Yes the genotype and whether there is cirrhosis or no cirrhosis. And then you are often running.
JOSEPH: There is a point there that the scripts are only dispensed monthly and that is the same for an S100 authority through your hospital pharmacy and the community through an S85 because each bottle of pills is pretty expensive so that is one way of tracking compliance and keeping the patient engaged.
MARIE: Yes, yes. Definitely. Now on treatment monitoring is not difficult, is it?
MARIE: So we talked about working the people up, full blood count, biochemistry, making sure that they have got that GFR of 30 that is sort of the cut off there, and whether their hepatitis C RNA is quantitative.
JOSEPH: Yes so knowing how much the hepatitis viruses and that really is relevant for that one small subpopulation of genotype 1 with less than 6 million IU.
MARIE: Yes, okay. And then one month later liver function tests but also it is really important while they are on treatment to check how they are going on the treatment. Are they managing to take the tablets everyday? Are they having adverse effects? Drug to drug interactions? Also what are the new medications? Then ask if they have gotten anything over the counter, those sorts of things, liver functions tests again at the end of therapy. So there is not a lot of blood test which is great and you actually do not test of cure or see if there is a sustained viral response as it is called, for 12 weeks after treatment has finished.
JOSEPH: A question had come up about the acronym overload and what is an SVR? SVR stands for sustained virological response which essentially means undetectable virus 12 weeks after treatment, so that is what SVR means.
MARIE: Yes. Okay. Great. Good yes it is not a lot of monitoring. That is great.
JOSEPH: No it is not.
MARIE: Adherence. Ideally people should take all their doses but the occasional missed dose is not bound to cause a panic attack but the idea is to get them as close to 100% as you can, so you should be addressing adherence at every visit as well as seeing how they are going with the treatment and whether they are taking any new medications and whether they are getting side effects.
JOSEPH: Also I will make a point too, if someone forgets a pill then never to double dose.
MARIE: Do not double dose. That is a good thing to know. The mechanics of improving or maintaining adherence, so dosage boxes, always depict, linking it to a routine, using calendars, start dates, know when the start date is, when the refills are due, linking it in with their lab appointments and your appointments, mobile phone alarms, looping in with caregivers or mental health workers, peer support and even may be with their methadone clinic or with supervised dosing strategy. Yes that is an important thing though, do not double dose. Not like the pill is it? So there you go. Look I think you know anything that you can do just to cue into that person so that you can get them taking it every day is the great thing. Are most of them daily now? The treatments?
JOSEPH: Yes. So the Epclusa which I think most people will be using is the one pill and in that one pill it is a fixed dose combination pill containing two drugs, sofosbuvir and velpatasvir, so the pill burden is low.
MARIE: Great. Okay. We were talking about
JOSEPH: We were talking about the acronyms and we were talking about the SVR definition and which is the definition of cure as it is outlined here on that slide in case you forget. It is undetectable HCV RNA in 12 weeks post treatment and that is considered durable. Now there are a couple of things to remember too that the antibody test can remain positive after a cure and the antibody can persist for the rest of somebody’s life and it is really important that the patient understands that because hepatitis C antibody is a commonly ordered test and there can be misconceptions in the community about the meaning of that test so you cannot really, it is not a very helpful test in somebody who has been treated for hepatitis C. If people have ongoing risk factors for re-infection so ongoing injecting drug use for example, annual HCV RNAs are recommended.
MARIE: Okay. So we are finding 95% of people would be expected to have the sustained viral response three months after they have finished their course of treatment?
JOSEPH: Yes that is correct. That means that 5% of people will not.
MARIE: Yes, yes.
JOSEPH: Okay. So right now outside of the context of a clinical trial we do not have any treatment options but those salvage therapies are coming through and in this context that is time to refer as well. If you pick up a treatment failure it is not the end of the world. There will be options and it is time to refer.
MARIE: Yes. Now somebody said do you need to repeat the RNA or the PCR one year after treatment, no, unless they have ongoing tests for hepatitis B.
JOSEPH: Yes absolutely.
MARIE: Okay. And somebody asked what if they missed a week of their tablets. Would they have to start again?
JOSEPH: No. I think the recommendation would be just to complete the tablets, pick it up where you left off and continue and complete the therapy and assess again three months after that last pill for cure.
MARIE: Okay. Alright. So the post treatment follow-up, it really does depend on the fibrosis stage before they even started treatment. So really you have gone up from people who really had very minimal or no liver disease right through to people with cirrhosis here so if they started off with no cirrhosis, normal liver function tests and they are considered cured, they actually do not need clinical follow-up for hepatitis C unless they have ongoing risk factors. So you can discuss with them about moving on as hepatitis C, yes you have been cured.
MARIE: And it is really only managing on a case by case basis if people come back with
JOSEPH: Ongoing risk factors
MARIE: Yes. Yes.
JOSEPH: For re-infection. Yes that is correct.
MARIE: If I have abnormal liver function tests when you do that test, when I have a sustained viral response I think we are talking this being said look you really need to assess whether something else is going on.
JOSEPH: Yes. So by definition if the HCV RNA is negative at week 12 post treatment completion they are cured of their hepatitis C but you cannot send them on their merrier way like that first group you described. They have still got abnormal liver function tests so there might be a second liver pathology like alcoholic liver disease for example or even non alcoholic fatty liver disease.
MARIE: Fatty liver disease, yes, we see a lot of that now.
JOSEPH: We do. We do. So referring that patient on for gastroenterology or hepatology review is really important and depending on your comfort with liver disease exploring other liver diagnoses.
MARIE: And then the people with advanced fibrosis or cirrhosis and a sustained viral response, most of these people are going to be managed in conjunction with a specialist clinic but it is important because we will be doing some of the monitoring, we will be doing the six-monthly HCC surveillance, the checking for osteoporosis.
JOSEPH: That is correct, yeah and remember that this population is going to be looked after in a, or co-managed with a liver clinic so we will have an assistance in discharging all of that follow-up.
MARIE: Yes and I think it is great when they come in you will check if they have any swelling, check their weight, how is their cognition and thinking and having problems with bleeding, bruising and those sorts of things. Alright.
JOSEPH: So we are nearly at the end of the presentation. There were just a few resources to point out and wall charts that are available through the GESA website and they make-up part of the consensus statement from GESA outlining or guiding treatment for hepatitis C in Australia so they can be really useful resources to print out and have available, talk about your treatment choices and your pretreatment assessment, your treatment choices and how to look after these people on treatment. And as I said before there are lots of free online calculators. Here are just a few examples that if you put in your Google search APRI calculator, MELD calculator or Child-Turcotte-Pugh which is another staging calculator for chronic liver disease. You can access those for free online.
MARIE: Okay then we have got some hepatitis C online learning links there for you to look at ASHM e-learning, NPS, medicine wise, the hepatitis C web resources listed there and now we have got some patient support resource sites there that would be really helpful especially when you are first engaging with them, they will be very interested, several people wanting to know about what sort of resources and any information they can access so there are some good sites for you to recommend to them. Hepatitis New South Wales has a directory of local doctors prescribing HCV and dispensing pharmacies so that would be great so you can choose to have your name added to the directory of the hepatitis New South Wales website.
JOSEPH: Okay so look just to summarise the top from today we will look at this acronym tree so I think one of the take-home messages is that you have got to test people that you think are at risk and that is going to take an awareness of what those risk factors are and who those priority populations are. Remember that your hepatitis C antibody positivity needs to be explored with the second test, the HCV RNA. Okay? And we have already mentioned those priority populations, people who inject drugs are the biggest target. Now in terms of the work of, assessing whether fibrosis is present or absent or whether there is renal failure or an EGFR of less than 30, whether there is HBV or HIV co-infections, they are the group you want to refer on to a specialist care, so the vast majority of patients with hepatitis C in Australia can be treated in general practice. Then the drug-drug interaction is a really important reminder and the resource there just not to forget is the Liverpool University website and there is another link to that there to help you assess drug-drug interactions. Remember that approval process through the PBS authority line, the 1800 number, as you are becoming familiar and more confident with treatment and acquiring your 10 cases you can use the model of the remote consultation form from GESA and just remember that your prescription is going to be dispensed on an S85 authority through community pharmacy and then finally the points about tailoring your management and what you are going to when people are on treatment and it is worth pointing out that monitoring is really straightforward and remember that really important stage that there was a test at that time pointing to the 12 weeks post treatment which is when you can tell someone with great confidence that they have cured their hepatitis C with the course of therapy.
MARIE: That is so exciting.
JOSEPH: Yes yes it is a really positive impact and a positive thing you can do for your patients and remember that engaging with those patients that have been screened as having cirrhosis and participating in their care in an ongoing manner and being aware that there are going to be treatment options available for the very small number of patients that do fail treatment.
MARIE: So just some acknowledgements. The presentation was developed by clinicians representing ASHM, the Australian Society of HIV, viral hepatitis and sexual health medicine, ALA and GESA, the Australian Liver Association and the GastroEnterology Society of Australia, ASID, the Australian Society of Infectious Diseases, RACGP and the Kirby Institute. So there is broad input into this evidence-based presentation and we hope that you have satisfied your learning outcomes, so identifying the priority populations for testing, interpreting those test results, and diagnosing hepatitis C accurately and that is the serology knowing the difference between exposure and having chronic hepatitis C, assessing for liver fibrosis, complications and comorbidities, both for PBS requirements and knowing who to refer and how you follow up people and to initiate treatment, monitoring and following up according to the Australian recommendations. So I hope that these learning outcomes have been addressed and I think they have an anything to add their Joe?
JOSEPH: No I think that is perfectly clear.
Thank you everyone so much for joining tonight. That does bring us to the end of our presentation. I just want to thank Joe and Marie for joining us tonight. I hope you found it really beneficial. There were a lot of questions that did come through. We did not get to address all of them in a lot of detail so leave it with us off-line. We do have your details and we will do our best to get back to you via email over the next week or so. So if we did not answer anything do not distress, we will still be able to get back to you and just keep in your mind this is a CBD event. To be eligible for your points you will need to complete the evaluation. It should pop up on your screen once you exit the webinar. A leaflet will also go out and an email in about an hour’s time so so that is the end of tonight and thanks again for joining us. Enjoy the rest of your evening everybody.