Prevention Imperial experts press for eradication of viral hepatitis

 

Viral hepatitis is a major global public health threat, claiming an estimated 1.3 million lives annually. This staggering mortality rate rivals that of other significant infectious diseases such as HIV/AIDS, tuberculosis, and malaria. Among the various forms of the virus, hepatitis B (HBV) and hepatitis C (HCV) are the most lethal, accounting for 96% of these deaths. The viruses target the liver, often resulting in severe complications like cirrhosis and liver cancer.

At the forefront of combating this disease, researchers at Imperial College London have significantly advanced our understanding of its global burden and devised strategies to help reduce its incidence and related deaths. Their work underpins the World Health Organization’s hepatitis B and hepatitis C strategy for elimination and has been instrumental in highlighting the importance of scaling up prevention, diagnosis and treatment, particularly vaccination in low-resource settings.

A member of the communications team spoke to Professor Graham Cooke, Vice Dean of Research at Imperial’s Faculty of Medicine and the NIHR Imperial BRC Infection and AMR Theme lead, and Dr Shevanthi Nayagam, Clinical Academic and Consultant Hepatologist at Imperial’s School of Public Health, about the global landscape of the disease, and their important contributions.

With support from you and Imperial colleagues, the World Health Organization developed ambitious targets in 2016 to eliminate viral hepatitis by 2030. How close do you think we are to achieving this?

Dr Nayagam: My research is focused on bridging field epidemiology, modelling and health economics to guide policy translation towards viral hepatitis elimination. Our 2016 study with infrastructure support from the NIHR Imperial BRC, helped to inform the initial WHO elimination targets by using data to create a mathematical model looking at what intervention coverage levels were consistent with elimination. Our model showed that – on a global level – a target of a 90% reduction in new infections and 65% reduction in mortality could theoretically be achieved by scaling up the coverage of infant vaccination, birth-dose vaccination (vaccination given within the first 24 hours of life), use of antivirals, and population-wide testing and treatment.

We’re nearly a decade on and some progress has been made, but not enough. The latest estimates suggest that diagnosis and treatment rates for viral hepatitis are extremely low. For example, only 13% of those with HBV have been diagnosed and 3% had received antiviral treatment in 2022. While some countries are on track to accomplish some elements of the elimination targets, certain high-burden and low-income settings, particularly in the African region, are far behind because the interventions haven’t been scaled up sufficiently. For example, less than 20% of babies receive vaccination at birth in the WHO Africa region – this is well off the 90% coverage target.

Why do you think it took until 2016 to acknowledge the significance of viral hepatitis as a global public health threat?

Professor Cooke: There’s no doubt in my mind that the transformation in hepatitis C treatment is one of the biggest changes in medicine in the last 10 years and a change that helped with establishing these targets. It improved people’s ambition about what could be achieved, not just for individual patients, but also in terms of hepatitis elimination. Up until that point, treatment for hepatitis C had been challenging, expensive and not always effective.

Now, we have a shorter, well-tolerated treatment which can achieve a cure in a very high proportion of patients. For example, in my clinical practice in Paddington, I have a clinic that treats people with co-infection with both HIV and hepatitis C. I no longer have anybody with hepatitis C. That’s not to say it’s eradicated from the whole country, but for patients engaged in care, we now have better access to treatment. At the same time, there has been progress in hepatitis B, where we have a good vaccine and well-tolerated (albeit long-term) treatments. So, I think there was a transformation in ambition because of the new tools that have become available.

Almost 10 years on, how is your work feeding into elimination efforts?

Dr Nayagam: In terms of HBV, an area where there is a big research gap is the prevention of mother-to-child transmission (PMCT). This is a major focus of my work and I’m currently conducting a study in West and East Africa looking at the effectiveness of hepatitis B birth-dose vaccination. Most of the previous data was from Asia showing that vaccination within 24 hours of birth is effective at reducing PMCT risk. However, there wasn’t much data from the Africa region about how well it worked there, and lots of countries in the region haven’t scaled up birth-dose vaccination. Despite only costing $0.20 per dose, the coverage is only around 18%.

Our study titled ‘IMPACT-B’ is therefore trying to answer key questions about the effectiveness of HBV vaccination in Africa and is taking place in three high-burden settings: Gambia, Senegal and Ethiopia. This data, along with other emerging data from our group and others, is important to help countries understand the most impactful, cost-effective, and affordable way to scale up PMCT interventions to reach elimination.

We have worked with various governments and policymakers to use modelling as a tool to help decide what strategies are best for different settings based on the local epidemiology, health systems constraints and other factors (e.g. in China, South Africa and Senegal). Our hepatitis B model is also used as part of the Vaccine Impact Modelling Consortium and has been helpful to guide funding decisions.

What opportunities are there to create a more coordinated global health approach to the prevention and treatment of viral hepatitis?

Professor Cooke: There’s a lot that we can still achieve with the tools that we have. As I said for hepatitis B, we have a very good vaccine and I think the focus should be on ensuring that all countries can achieve high coverage. Another example would be the mechanisms that can be put in place to ensure that treatments are affordable. The Medicines Patent Pool organisation works to get licences to manufacture essential medicines for use in low-income countries at reduced costs. This has really driven down the costs of drugs in various countries.

The change in price of hepatitis C drugs, for example, is quite remarkable. When they were first launched 10 years ago, you’d be paying sometimes $150,000 for a course of treatment. Now, for example, the same treatment is effectively available for $50 in Pakistan.

Progress made over the past decade has highlighted the importance of a multifaceted approach. Why is interdisciplinary work so important when it comes to tackling this sort of public health issue?

Dr Nayagam: The nature of the challenges within viral hepatitis are diverse and include data uncertainties, logistical, funding constraints and political factors. It is therefore important that we’re able to understand the different nuanced factors, as it is not just one single thing that’s stopping progress towards elimination. Therefore, I think that multidisciplinary approaches are really important.

My research combines clinical research, modelling and health economics to guide policy translation. It’s also vital that we are able to work with the communities that are affected, as well as stakeholders such as Ministry of Health officials. Only then can we design the studies, evaluations or analyses needed to make real change.

Professor Cooke: To tackle public health challenges like viral hepatitis at a systems level, you need a multidisciplinary approach. We’ve probably done more than most institutions in the UK to tackle hepatitis, but we’re just one player in an ecosystem. The same applies for a range of infectious diseases such as tuberculosis and malaria.

What are your future research ambitions?

Dr Nayagam: I think there’s still scope for more research, especially on the prevention of mother-to-child transmission in Africa. We now have some good interventions available to reduce HBV mother-to-child transmission, including birth-dose vaccination and antiviral prophylaxis in pregnancy. However, there is this large implementation gap meaning that they are not sufficiently scaled up where they are most needed.

I therefore want to use my research to understand how models of delivery of PMCT interventions should be tailored towards African settings to reach more people, particularly in rural areas. For example, should we continue to use a ‘one-size-fits-all’ approach? Or should strategies be implemented in different ways in different settings? And how can we do this in a way that not only helps reduce babies being infected and represents good value for money, but also represents equity and fairness?

I’d like to think more about rural populations and how we can improve coverage there, and whether different strategies should be implemented to reach more people in a way that represents equity. Should we offer more outreach interventions or use new, innovative tools that are in the pipeline that could help decentralise and deliver care in the community. For example, rapid diagnostic tests can be used instead of laboratory assays to test for HBV viral load, or microarray patches for delivering birth-dose vaccination instead of traditional needle and syringe methods. These methods might cost more but may let you reach more vulnerable and remote populations.

“I’d like to think more about rural populations and how we can improve coverage there, and whether different strategies should be implemented to reach more people in a way that represents equity.”

Also, in settings where hepatitis treatment is not free and people have to travel long distances to get care, some patients are spending a large proportion of their household income on their health, which may be driving them into catastrophic health expenditure. So, my research will also be looking from an equity perspective at how strategies can protect households from suffering from the health and economic consequences of viral hepatitis.

What should we really focus on for this year’s World Hepatitis Day?

Professor Cooke: We can never underestimate the relatively low profile that viral hepatitis has in global health. But I think it’s important to celebrate the progress that’s been made in a relatively short space of time, particularly in the UK where there’s been tremendous progress on hepatitis C. However, globally, I think there’s still a major challenge of disease, and it needs greater focus. We have the tools, and many countries have the resources, but it needs political will and national leadership to make it happen.