Hepatitis C elimination

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Hepatitis C has been a substantial burden on our healthcare system and in our community for such a long period of time, as it remains for much of the world, particularly with the related hepatocellular carcinoma in mind. In recent years however something incredible has happened. Directly acting antiviral therapy has meant the possibility of a widespread cure to become relatively quick and easy for the right price.

In March 2016, Australia embarked on a transformative mission to cure hepatitis C in as many people as possible with view to eradication. So five years later, where are we at? I'm David Liew your host for today. And I'm very glad to be speaking to someone who can speak to this issue unlike anyone else. Professor Gregory Dore, an infectious diseases physician from St Vincent's Sydney, is a program head of the Viral Hepatitis Clinical Research Program at the Kirby Institute at UNSW and, amongst other things, a world leader in hepatitis C elimination strategies. He's written on this subject to Australian Prescriber and I'm very glad to welcome him to the podcast today. Great. Thanks for joining us.

Thanks very much David.

Perhaps you can illustrate to us why this is such an important issue. Why is eradication beneficial for patients and why is that the right strategy to go about trying to do things?

I suppose just a little bit of background that led into the program commencing in 2016. I've been involved clinically in hepatitis C for 20 years. And going back to the late 1990s, people were treated for hepatitis C in relatively small numbers but with interferon injections, very, very difficult to get through treatment. The success rate was really quite poor with interferon alone. It was really only 10% cure rate with six or 12 months of therapy. Then we added in ribavirin as a second agent. That improved things somewhat to around 40%, but still a real struggle like six to 12 months of a lot of side effects, a lot of fatigue, some psychological side effects. And it really was a tough road for individual patients. And we were treating in Australia, maybe two to 3000 patients a year on the back of that sort of therapy.

So to have such a transformative opportunity where you go from that situation to a situation where you've got a highly curative therapy to 95% or above with two or three months of oral therapy with minimal side effects. It's really incredibly remarkable to have that opportunity to cure hepatitis C, which for many of them was causing significant symptoms, was causing considerable concern around what the future may hold in terms of advanced liver disease complications. So yeah it was a remarkable time when it arrived. It's been an incredible journey since and really grateful that Australia’s had this opportunity.

Why wouldn't we just treat this on demand? Why would we go about trying to actually eradicate hepatitis C? I think that might seem obvious to some, but I think there's a real cost differential between these two approaches potentially.

Sure. I think it's important to look at things at the individual and the population level. And I'm fortunate, I suppose, being a clinician and also a public health academic, that I do look at things from those different perspectives. So as an individual patient I mean the key is to cure their hepatitis C if they're at risk of ongoing exposure, reinfection to try and limit that risk. And then if they're reinfected to offer them treatment. So at the individual level it's relatively straightforward. So you inform patients of the benefits of this new therapy and the prospect's cure. There're not many people that say no. So that's a pretty simple equation, a very unusual equation, really, in the context of medicine. Here's an opportunity to cure a chronic infectious disease you may have had for decades with this two or three months of very, very well-tolerated therapy. That side of things I think is pretty straightforward.

So then the population-level strategy is, okay, if we can cure people at the individual level and we can provide the broad access points, we can actually turn this epidemic around. So an epidemic of hepatitis C that was increasing in terms of numbers infected, increasing in terms of advanced liver disease, so liver failure, liver cancer and liver-related death numbers prior to 2016. So a real public health concern. But with this new therapy we absolutely had the opportunity to turn things around and to potentially break the back of the epidemic. So to really reduce transmission of hepatitis C in the community, to a point where in conjunction with our harm-reduction strategies that we have for people who inject drugs, adding this treatment on top of that provides amazing prevention capacity. So reducing individual risk of liver disease at the population level, having an impact on the epidemic in two ways, reducing number of infections that are being transmitted and at the far end, reducing the liver disease burden that arises from those infections.

I think that there's a lot of talk at the moment in the context of COVID and the stage that we’re at in the pandemic about what eradication means and how sustainable that is. Were you always confident that hepatitis C eradication was something that might be possible in Australia? I know we're clearly not there yet, but it's an exciting prospect.

So just a little on terminology, I don't tend to use eradication. Eradicated infectious diseases is a very, very small list. Smallpox is the only one that sits on that list. So elimination is a somewhat lower bar. So elimination in the context of infectious diseases is actually getting infection or disease down to zero levels in a particular population or geographical setting. That's even pretty tough in the setting of hepatitis C, and in fact the WHO in defining their elimination goals have not talked about getting it down to zero in different areas. They've talked about reducing the number of new infections by 90%. They've talked about reducing the numbers of liver-related deaths by two-thirds as the goals that they've set for 2030.

So I don't think with the treatments that we have and with the harm-reduction strategies that we have that we can stop infection completely. I think that's a huge, huge ask but I think we can get transmission levels down to a point where there's not large numbers of people becoming infected every year. And it's a very, very, very manageable infection then because of the curative nature of these treatments.

Absolutely. How did starting on this journey become possible in Australia five years ago?

Yeah. I think there's some key elements that Australia has provided in terms of the foundation. So I think Australia has always been pretty strong on the prevention side, so that's the first thing to say. So we had implementation of Needle Syringe Programs since the early 90s broadly available across the country, funded by the Federal Government, really pivotal to prevent HIV epidemic amongst people who inject drugs. And then also having a contribution in terms of prevention of hepatitis C, so that's really important. We also had pretty decent drug treatment programs in terms of methadone and buprenorphine available. So those elements of harm reduction were a key foundation. We also then had very good data. So Australia I think does epidemiological data collection pretty well. And we do some really good modeling. So we had a good understanding of what an epidemic was, the size of the epidemic, who was infected, how things were moving along in terms of escalating numbers particularly advanced liver disease.

So that helps frame what was required in terms of the numbers, and that was really important I think for the government to look at funding a major therapeutic intervention through the PBS. And then we had I think absolutely important skills within the government to negotiate on price. So I remember back in 2014, 2015, a lot of discussion including the pharmaceutical industry advisory boards and so forth about how are we were going to deal with a high-cost item, which initially was $70–$80,000 per course in the United states, and a higher demand given the large number of people that would be keen to get treated. And there was a lot of discussion that we should be focusing on people with advanced liver disease, with cirrhosis. And that should be the target for the initial few years of the program which had been the case in other countries around the world, because of high costs they'd said, "let's just focus on those that need it the most". But Australia had a different approach and I think absolutely the right approach. They felt that, "okay, we're keen to make a big investment in hepatitis C treatments, we've got a billion dollars or more, rather than paying $40– $50,000 a course, which might enable people with advanced disease to get treated, let's bring the price down per patient to say $10–15,000 per patient, and then we can treat a much, much larger number of people across the disease spectrum".

In terms of the drug companies, they get a really decent return on their investment. In terms of individual patients, they have an opportunity to have access to these amazing new therapies, and in terms of the government, they have some security around the budget impact. So they also built in a sort of a cap in terms of the annual expenditure that could be paid to the drug companies. So those three elements I think were really crucial in developing a world-leading program, and many countries around the world looked at what we had rolled out in 2016 and thought, "oh, why can't we do this?"

And so this Netflix model for drug funding is this something now that has been more broadly adopted in other countries like you've mentioned?

Absolutely. It's been adopted by individual countries. It's also been adopted by states within the United States. So there's been a range of different arrangements that had flown I think or come from where Australia led. And I think the key to all of this is, as I said, everyone's a winner. I mean in terms of larger number of patients treated, the drug companies getting return on their investment, and it's a really good model to go forward with, and it's just common-sense public health. And I think Australia has done that side of things very well. The other important component of that model was to, okay if we develop this arrangement then we need as many people as possible to get involved in the treatment side. So the fact that they enabled non-specialists, so primary care practitioners, other physicians, to prescribe direct-acting antiviral therapies from day one basically was essential to the success of the Australian model.

Now in those initial months, GPs needed to get some approval from the infectious diseases or gastroenterology specialists in terms of what they're prescribing. So that was an important mentoring and oversight component, but then now as I'm sure everyone's aware in fact the majority of people are treated by primary care physicians and the model has gone incredibly well. And despite some specialists, in those early days, thinking the sky was going to fall in because GPs were prescribing DAA therapy, it certainly hasn't fallen in. And I think Australia’s benefited enormously from that diversity.

Absolutely. Which goes to show the power of enabling a primary care workforce in trying to tackle this type of public health problem. How has it gone five years later now? How are we tracking? Has it gone better or worse than we thought?

We treated 36,000 in 2016. In fact, we treated 36,000 in 10 months of 2016 from March to December. So incredible start to the program, not surprisingly the numbers have come down since then. But in the five years of the program, we've treated around about a 100,000 people. And that looks like it's at least half of the people with chronic hepatitis C. So that's really impressive. And there are some concerns that the numbers being treated per year have come down in recent years and there's a lot more work to be done. But if we sit back and look at the first five years of the program, amazing success in terms of numbers treated. Amazing success in terms of turning around escalating rates of liver cancer, and liver failure, and liver-related deaths. And absolutely early indications that numbers of new infections that are being acquired in Australia is also trending down. So all the things that you would want to achieve over that five-year period I think.

Absolutely. Well with that kind of early success I think it almost sets up expectation even higher with people who thought this might not be possible at all now eyeing off elimination as a real possibility. I mean do you think that the path from here is straightforward and smooth?

No, it's not straightforward. And on some levels it'll get tougher and that's natural in the sense that you think the early adopters, people coming forward for treatment, may have had less issues in terms of other health problems, other socioeconomic issues that they've had to deal with. So it will get tougher. We've done incredibly well in terms of uptake amongst people who inject drugs, but we need to continue to do that. We've reduced the amount of infection in that population from around about half of people who inject drugs having active hep C infection down to under 20%. So we're sitting at around about 18%. So well over halving of that, but there's still this important pool there to engage with. And we need to be more innovative in terms of how we do that.

So a few things that we're trying to do, one is to provide opportunities where people interface. So for example, if someone who develops an injection-related infection is hospitalised for cellulitis, or endocarditis, or osteomyelitis, we're trying to develop projects that provide rapid screening and treatment initiation during that hospitalisation. Another thing we're trying to do is more rapid screening in the prison setting, particularly in remand prison where people can come and go within weeks or a few months rather than longer incarceration periods. So screen people on entry, initiate the therapy then it's straight up. And where there’s only two months required for one of the regimens, you can get that completed for the vast majority within that sort of timeframe.

And also through Needle Syringe Programs, that more innovative approach where we screen people and get them onto treatment with peer support. So we're looking at those sort of models of how to make it a bit easier to reach the harder to reach populations. There still needs to be some work done in what you might call more general primary care practices and services because there still are people out there who haven't taken the opportunity to come forward for therapies. I think we need a lot of education around that, both at the patient level and also at the practitioner level.

You've written quite extensively about trying to target people who are otherwise vulnerable in those kinds of situations, you’ve written in the New England Journal [of Medicine] about this and quite broadly. And then yet as well there's this other cohort of people who may not necessarily meet those kind of conventional definitions, but who may have had longstanding infection. Do you think that we're going to be able to address both of these cohorts similarly? Which one do you think we're really going to have the better success in going forward? And what can we do about that?

Yeah. I Think there are two arms of what's required going forward. Look, they're clearly different populations even though they are somewhat overlapping. I think for the group of people who injected drugs or people that acquired their infection overseas, for example migrated to Australia, and there are a significant number of those people, we knew we needed some specific campaigns. But when we've looked at the treatment uptake throughout what we call our data linkage projects, we have found some gaps and those gaps include people who've been born overseas having a somewhat lower treatment uptake, people that have experienced homelessness and, starting to emerge a little bit, indigenous Australians as well.

So there's some key strategies around those different populations. I think some targeted education campaigns are really important for the overseas born and for the broader population. For the homelessness-experienced population and for indigenous we again need some very specific and targeted programs that provide those access points. I try and be an optimist and I'm pretty optimistic going forward. That as long as we continue to innovate, as long as we continue to build a diversity and number of potential access points for treatment, then I think we'll do okay.

And I guess there’s still always the issue of primary prevention as well in amongst talking about the challenges to elimination at the beginning, that's still an issue which we need to be conscious about given that there's still quite a large number of people out there with hepatitis C.

Yeah. Look the primary prevention obviously is essential going forward. I'm not concerned, as others have been, about things like reinfection. I've always expected some re-infection cases to come through. I mean you treat people who become reinfected, they're very easy to treat, they haven't got resistant virus, they've got a new sort of wild type virus. So it's not a complex management scenario. Treatments worked very well and some people need to be retreated a second time. So that's not a concern for me and the government arrangement allowed for that to happen which was essential. And once we reduce the pool of active infection, continue to drive that downwards, in fact the risk of reinfection comes down. So we'll see less and less cases of reinfection because of that smaller pool of active infection. But the maintenance of that foundation of primary prevention is essential, not just for hepatitis C but HIV, and to have that interface with people who inject drugs, a clearly highly marginalised population.

Do you think that we've learnt lessons from this that we could apply elsewhere? Because I mean this really objectively is an international success story. Should we be taking what we've done here and trying to apply some of it in other challenges in health care?

Look, I think the lessons are to be ambitious, to look at public health in the context of striving for really important targets. Now, look we might not reach them. And I'm pretty confident still that we’ll reach the WHO targets, but the really key thing is to have the ambition to do that. And look, to segue a little bit to COVID, I've found some of the ambition around COVID to be not as impressive in terms of our vaccination strategy obviously. I think in public health, it's great to set goals and targets and really try and strive for them. I mean the one area in all of this I'm still concerned about is I think we do need to do a lot of work on is indigenous Australia.

We are seeing some increasing numbers of infections, particularly in younger Aboriginal people. And I think we need to do a lot more there as a key population group going forward. But getting back to the original question about what lessons can we take. I mean the other lesson is that a partnership approach, and we've seen this in HIV prior to hepatitis C, really is the way to go. So the involvement of community, clinical, academic, government and other stakeholder groups getting together and developing strategy and working together on a lot of this.

That's a model that's not unique to hepatitis C but is a model that I see more and more actually in public health. I review grants for NHMRC. And one of the key elements that they're really looking for now is what they call end-user involvement. So involvement of the affected community. And that's something that we've done for a long time in HIV and hepatitis C. And it's a very natural partnership that we've had. And I think that's a little bit foreign to some other areas of clinical medicine. So you learn a lot from partnerships with the affected community, and it's a very much two-way interaction. And it's a really valuable component of the overall strategy.

Well, that's a really nice message to hammer home at the end. Thank you so much for all the work that you and your colleagues have done so far. Good luck with the progress in the future. And thanks for joining us on the podcast.

A pleasure David and final message to prescribers out there who may not have climbed onboard the hep C elimination wagon, so to speak. Get involved, it's a great era of clinical medicine, incredibly empowering and very fortunate to have this opportunity,

Absolutely time to be part of the success story. Thank you so much.

Thanks David.

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The views of the guests and the host on this podcast of their own and may not represent Australian prescriber. I'm David Liew. And thanks for joining us on the Australian Prescriber Podcast.