Can the US Replicate India's Hepatitis C Eradication Model?

Madhumita Premkumar, MD

Credit: LinkedIn

Real-world data to be presented at The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD) in Boston this weekend further supports an elimination model for hepatitis C virus (HCV) that has become gradually implemented across India to significant long-term benefit.

Analysis of the Punjab HCV Elimination Model, presented by Madhumita Premkumar, MD, associate professor in the department of hepatology at the National Academy of Medical Sciences in India, address the effect of cost-efficient direct-acting antiviral (DAA) rollout on a national population’s rate of HCV-related decompensated cirrhosis in the new AASLD data.

In an interview with HCPLive during The Liver Meeting, Premkumar previewed the presentation and discussed in detail the design, intent and history of success with the Punjab Model.

HCPLive: Can you explain this project and some of the specific demographics and clinical presentations that we see within this cohort?

Premkumar: This project started all the way back in 2016. What happened is that we realized there was a large, untapped population count of hepatitis C and B in India. When direct acting antivirals became available, we realized this is a great opportunity to actually stamp out this curable disease from the population. So in 2016, the government of Punjab actually gave a lump sum of 200 crores in Indian money, which would enable the health services to purchase drugs—and generic drugs are available in India at a very good cost, and they are bioequivalent and very efficacious.We gave it to our patients, which would finally cost just $60 for the entire course. And we realized that our population prevalence based on sampling was around 3.6% in the state of Punjab. This was done by a randomized sampling of urban and rural areas.

So if we talk about the demographics of our population, I would say about 80% of the patients who actually took treatment on the program were from a rural or agrarian background. So rural, semi-urban, most people are just school-educated, literate. And we don't have so many in the urban areas actually taking advantage, possibly because they already had access to treatment and medical facilities, which are not in the government sector. So our idea was to get it out to the patient population in the rural areas, because that's where the transmission is occurring. And another interesting fact about hepatitis C in India is that it's primarily transmitted by unsafe injection. There is a tendency to get injectable drugs for even minor ailments, which is a population-based necessity. They just assume that they would require injectable drugs for even minor ailments. And if you compare it with the Egyptian program, most patients were actually infected in Egypt by the Schistosomiasis immunization campaign. So they use the same scarification needles in a large section of the population.

After we tested and treated this large population, we found our cure rates in the general population were 91%, which is really good considering our adherence would be a problem. And then we were hit by the COVID crisis in the middle, so our adherence is about 88%. And even with 4 weeks and 8 weeks of therapy, we have cure rates of 88 - 91%. We were very happy with our results. So once this one state and India actually showed us results, we replicated the program across the country with the national viral hepatitis elimination program. This model is now carried out across the country. And the beauty of it is that it's done in a decentralized fashion.

So what we did was we trained doctors in existing districts, and then we enabled pharmacists and the local physicians. We trained them first in a workshop, so they were taught about hepatitis C and how the drugs would be dispensed, and which patients could be treated by them. We requested that patients who did not have cirrhosis would actually be treated at the periphery. Then patients who have compensated cirrhosis, they will be given a specific regimen, and the ones who decompensated cirrhosis who have treatment failures or who have any complication like hepatocellular carcinoma, HIV co-infection or hepatitis B, they will be referred to us.

This hub and spoke model, which is similar to the ECHO model, which has been used in the US in some districts, was used across the country, and we have a 91% cure rate. So this started way back in 2016 and the data we're bringing to the AASLD this year is about decompensated cirrhosis. We are actually showing reduced severity of liver disease—patients don't have any more variceal bleeding and they are actually off transplant lists. All of this at $60 per patient. So, it's an enormous program and actually shows the way that drugs should be made available, where they're required.

HCPLive: How much of the issues that we see with hepatitis C eradication in countries like the US—where pharmacotherapy is capable but rollout and access is still inadequate—can be chalked up to policy or public health limitations?

Premkumar: I mean, the patent laws work to some extent; obviously, companies need to get back their investment that has been used in drug development. But at a certain point, the government or the public sector needs to take over and see what are the requirements of their population. If people need it, and people are suffering, and it's avoidable by a very low-cost purchase, it should be done. There was a lot of resistance to free drugs for HIV. Thankfully, we come under welfare society and our governments are having public sector hospitals, which are largely free of charge. So all of these services testing, dispensing of drugs, they are now using this existing infrastructure at no charge to the patient.

This is a good way to motivate people, and with this program, not only will we be giving drugs—we're also vaccinating for hepatitis B, we were screening family members and linking them to care. We were integrating and rehabilitating patients who use drugs. They were linked to opioid substitution programs and needle exchange programs. So there are huge benefits even in these micropopulations. We also use the program to dispense DAAs in the pediatric population. And it was the first data set that came from the pediatric population, from Punjab.

HCPLive: As you're saying, any interaction of care to this extent is also conducive to other opportunities to ensure better overall and preventive health in a population. Are we anticipating more long-term data and findings from this project, extrapolated over the years?

Premkumar: This is a long cohort. It's not just for hepatitis C. It's also hepatitis B. We also presented that this would actually be reducing the number of liver cancers that pop up later in our population, because patients who come for hepatitis C treatment are also informed about the ill effects of alcohol. And patients who have diabetes are also at increased risk of cancer, so they're offered free surveillance services for HCC under the program. So, all of these new ramifications of the programs are come to being from what was a simple idea to just eliminate hepatitis C as per the WHO requirement of 2030.

Egypt's been more on track. I think we were disrupted by COVID-19 to a large extent, because patients had lockdowns and there was an issue with adherence, with coming to get their refill of the prescription. But what we showed in the program that in an average individual who does not have risk factors, even 4 weeks of therapy had a 77% cure rate, even 8 weeks of therapy had an 88% cure rate. And of course, everyone who completed the 12 weeks, 91.6% cure rate. So, even if patients miss drugs, there were opportunities to get them back in treatment. But I would really commend the spirited exercise that were done by our physicians. They really work to get the patients back in, inform them, educate them and make sure all the drugs are taken on time.

HCPLive: As you noted, this is a global eradication goal, so this is great to highlight for any society combating hepatitis C cases and progression. Is there anything else you would like to add?

Premkumar: I am surprised that the US has not taken up the program in such a way. I mean, countries like Australia, even smaller countries like Ireland, are well on their way to elimination. Egypt has eliminated with I think one-eighth of the GDP of the US. So I find it quite astonishing that these drugs are not made available to people because this is something that prevents death, something that prevents a lot of disease-related burden on society and disability-associated life disruptions that are occurring to people. And it would really bring a good amount of restoration of health services, rather than dealing with decompensated cirrhosis, increasing transplants, increasing cancers in the community, it would be much better to nip it in the bud.