Hepatitis B treatment is being scaled up, which could turn the tide in endemic regions. A Crick-led project aims to understand the impact on African populations.
The World Health Organisation (WHO) has outlined an ambitious target to reduce viral hepatitis infections by 90% by 2030, aiming to eliminate the threat to public health. To support these targets, recent WHO updates to guidelines for the treatment of hepatitis B virus (HBV) relax the criteria so that more people could benefit from life-changing medicines.
The B-ZERO team
But, as head of the Crick’s HBV Elimination Laboratory, Prof Philippa Matthews points out, challenges remain. “There are gaps in our understanding of the diverse hepatitis B treatment outcomes, and whether different viral strains are able to develop resistance to drugs more easily,” she says. “So, we can’t just change a policy and hope it’s going to work seamlessly.”
To forecast what treatment expansion could mean in practice, a new Wellcome-funded project called B-ZERO unifies an international team between the Crick, Vestfold Hospital Trust, the University of Addis Ababa, the University of Stellenbosch, the University of Cape Town, and the University of Bristol.
Focusing on two HBV endemic regions, Ethiopia and South Africa, the programme will investigate the response to a first line treatment for hepatitis B, tenofovir, which is also used to treat HIV. This involves expanding and analysing a huge repository of patient data collated by a pan-Africa consortium called HEPSANET, a ‘living registry’ for HBV, developed by Prof Asgeir Johannessen working between the University of Vestfold and the University of Addis Ababa.
In clinical research sites, the B-ZERO team will gather health and demographic information, working to understand barriers to accessing and taking consistent therapy. They’ll focus on assessing the impact of co-existing health conditions and the effect of suboptimal drug concentrations.
At the same time, part of the team will also be examining the biological aspects of the virus itself. “In our lab at the Crick, we’ve been working on a streamlined way to sequence the hepatitis B virus and work out how the genetics of the virus impact different disease outcomes, and its response to tenofovir,” Philippa says. “We will also measure a range of viral and immune biomarkers, and use new HBV in vitro replication assays to quantify drug susceptibility.”
Led by researchers at the University of Bristol, the team will then combine these data into a mathematical model, to make predictions about what is likely to happen to population prevalence and outcomes of infection in different settings as treatment is scaled up.
Drug resistance is an important focus for the international team. As Philippa explains, it’s easy to observe resistance in small data sets, but to what extent it’s widespread in the population, or a threat to elimination goals, remains unknown. “Following more people over a longer period of time in this new project will enable us to understand drug susceptibility at the start of treatment, and how this may change over time with therapy. We’ll be looking at how this is influenced by viral reservoir, genotype and immune responses.”
Taking this holistic approach will allow the multidisciplinary team to report back to WHO and policymakers and inform treatment implementation over the course of the project. Community patient representatives and civil society organisations are embedded in the project team in order to support approaches tailored to the needs of the local settings, and representing the needs of people living with HBV.
“There’s lots to be optimistic about if we scale up treatment, as we know it can reduce liver disease,” says Philippa. “But there is a risk of scaling up in a naïve way, without understanding the barriers in access, or tackling incomplete treatment responses.”
“As new hepatitis B treatments become available, we’ll also now have agile infrastructure in place to understand the impact of new interventions, to help accelerate advances towards elimination goals.”
