“This couldn’t be more pressing: recent research from our lab showed that a stark 1% of clinical trials for HBV take place in the World Health Organisation Africa region, despite it bearing an estimated 70% of new HBV infections worldwide,” explains Marion Delphin,  postdoctoral researcher in the HBV Elimination lab.

HBV is a virus that infects the liver and can lead to serious liver disease if untreated. Although possible to prevent through a safe and efficient vaccine, inadequate roll-out has left some communities more vulnerable to the spread of HBV. 

Once someone is infected, HBV cannot be cured, but can be controlled using some of the same drugs as for HIV, which reduce the risk of long-term complications, and also lessen the chances of passing the virus on. Various cure strategies are being tested in clinical trials. 

An imbalance in research and disease burden

Published this year in The Lancet Gastroenterology and Hepatology, the lab worked with Stellenbosch University, the African Health Research Institute (AHRI) and the Kenya Medical Research Institute (KEMRI) to highlight the underrepresentation of HBV research in Africa. 

The researchers searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for HBV Clinical Trials between 1980 and 2023. Out of 1804 clinical trials identified, only 18 took place in the WHO African region – fewer than 1%. In the same region, the number of HBV clinical trials also compared poorly to other diseases including HIV, COVID-19 and malaria, despite ambitious goals for elimination of HBV infection.

Marion says: “HBV is often called the ‘silent killer’ – it kills 10 times more people than HIV. Although the COVID-19 response was a unique global effort, it’s still shocking that, in the WHO African region, there were nearly 300 studies for COVID-19 in just three years compared to 18 for HBV in over forty years. This shows that clinical trials for infectious diseases are possible, but the virus has been neglected by national and international agencies and governments. There are significant barriers which we need to break down.”

A stigmatised disease

Marion believes that the lack of HBV research comes hand-in-hand with the perception of the infection in the community. Most HBV worldwide is now transmitted from mothers to babies at birth or in very early life, but as HBV can also be spread through sexual contact or from needles, it comes with significant stigma, holding people back from seeking help. Even if they do, the requirements to be eligible for HBV treatment are so narrow that only a minority meet the criteria. And for those who are given medication, problems with stigma mean that people may not take medication for fear of their families finding out.

Marion said: “It’s really important to understand what it’s like to live with the virus and what challenges people are facing. It’s not as easy as telling people what the symptoms are and how to get tested. We’ve heard stories of employers asking employees to disclose their status, which could explain why someone doesn’t want to be diagnosed.”

The EVOLVE-HBV study

The Evaluation of Vukuzazi Liver Disease (EVOLVE)-HBV study has been set up as a collaboration between the Crick, UCL and the AHRI in Durban, South Africa. Involving a diverse team, it aims to capture a picture of HBV infection in the KwaZulu Natal region of South Africa. Researchers will set out to map the distribution and impact of HBV in this community, and use this to inform better approaches to clinical care and treatment.  

Motswedi Anderson, a postdoc in the HBV Elimination Laboratory, is leading the EVOLVE-HBV project. She said: “Our ultimate goal is to improve HBV care in South Africa. A crucial part of the study is engaging with the community, and involving them as codesigners in the research. We've already identified some initial barriers, such as a lack of knowledge about what causes HBV and how it spreads, or financial difficulties which restrict people from accessing help.”

The team hope that, by laying this groundwork and creating a more permissible environment for HBV research, initial steps can be taken to close the gap between the number of clinical trials and the burden of disease. They are keen to ensure that the voices of people with lived experience of HBV are at the heart of the project.    

Updating treatment guidelines

HBV is a global issue, and researchers are looking to involve people with lived experience to identify and tackle local issues wherever they arise.

“Even in the UK we have problems with access to HBV medication,” explains Philippa Matthews, Group Leader of the HBV Elimination Laboratory at the Crick. “The narrow guidelines for treatment eligibility are under review and the hope is that better access to diagnosis and more relaxed criteria will be developed which allow more people access to treatment. But it will be really important to include the perspectives of people living with HBV in this process of change.”

A right to research 

This World Health Day, the researchers at the Crick hope to draw attention to this critical lack of investment in HBV research in the WHO African region and highlight that people living with HBV in all communities have a right to be prioritised in clinical trials.