A new international research collaboration – B-ZERO – has secured a Wellcome Trust Discovery Award to investigate why some hepatitis B patients fail to suppress the virus despite receiving treatment. The Stellenbosch University-led study also involves the Universities of Cape Town, Addis Ababa, Bristol, and Oslo, as well as the Francis Crick Institute, a leading biomedical research centre in London, and the Vestfold Hospital Trust, a Norwegian public health trust.
The team will study patient responses to tenofovir, exploring factors like drug concentrations, access to treatment and differences in African HBV strains, with the findings aiming to improve hepatitis B treatment outcomes, reduce liver disease and cancer risk, and strengthen efforts to eliminate viral hepatitis in African health systems.
Several serious questions remain unanswered regarding the treatment of patients with hepatitis B. For instance, why do some patients who carry the virus suppress it while receiving treatment, whereas others do not?
Could it be that they don’t have the correct concentrations of the drugs used to treat the virus in their blood to be able to suppress virus replication? Or is there something about the HBV strains in Africa that differs from those in with other places?
The work will focus on regions where HBV is endemic in Ethiopia and South Africa, and the researchers will investigate patients’ responses to tenofovir, a first-line treatment for hepatitis B that is also used to treat HIV.
Professor Tongai Maponga, associate professor in the Division of Medical Virology and Head of the Viral Hepatitis Research Group at Stellenbosch University, described the Wellcome Discovery Award as a “highly prestigious and highly competitive grant”.
“It will help us continue, and build on, the work we’ve been doing on viral hepatitis in South Africa, in Africa and globally,” he said.
Maponga, who is also a senior medical scientist at the National Health Laboratory Service, said the work of his team at Stellenbosch focuses largely on “understanding viral hepatitis in African settings and translating that evidence into improved prevention, diagnosis, treatment and policy”.
“Our vision is a world where no person suffers from viral hepatitis, and our programme is centred on what works in real African health systems.”
He described chronic hepatitis B as “a silent but terrible disease”, adding that an estimated 2m to 3m people in South Africa are infected.
“One of the consequences is that it causes liver disease, including cirrhosis, and may lead to primary liver cancer, which affects people at a relatively young age, even in their 20s. After diagnosis with primary liver cancer, they barely survive for six months: most die within a year because of late diagnosis.
“We have various tools, including a vaccine, but this only started in 1996, meaning there are still many people who were not vaccinated and could be infected, and so a huge number who need to be diagnosed and treated.”
When treating the disease, it’s important to ensure that the viral load is suppressed, and he said that achieving viral suppression drastically reduces the risk of developing liver disease and primary liver cancer.
“This research will answer the key question: why are some patients unable to achieve viral suppression?”
Besides the research into this question, the study will also draw on data from HEPSANET, an existing longitudinal registry of patients with viral hepatitis in several African countries, including South Africa, to help gather information on some of the factors predicting treatment outcomes.
Maponga said he was delighted that the Wellcome award will bring together local colleagues from Tygerberg Hospital, Groote Schuur Hospital, the University of Cape Town and Stellenbosch.
“We tend to work in silos, so we don’t always speak with the same voice to draw attention to important matters,” he said. “With this grant, we can change this tendency.”
Professor Philippa Matthews, head of the HBV Elimination Laboratory at the Francis Crick Institute and leader of the B-ZERO research project, said the work will involve expanding and analysing HEPSANET’s huge repository of patient data.
“There are gaps in our understanding of the diverse hepatitis B treatment outcomes, and whether different viral strains are more likely than others to develop resistance to drugs,” she said.
The B-ZERO team will gather health and demographic information in clinical research sites, 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 on treatment outcomes,” said Matthews.
At the same time, another part of the team will be examining the biological aspects of the virus itself.
“There is lots to be optimistic about if we scale up treatment,” Matthews said, “as we know it can reduce liver disease. But,” she cautioned, “there is a risk of scaling up in a naïve way, without understanding the barriers in access, or tackling incomplete treatment responses.”
See more from MedicalBrief archives:
The stealth and tragedy of hepatitis B in South Africa
New vaccines offer hope for Hepatitis B treatment in SA