EVoLVE Hepatitis B Study

What is Hepatitis B virus (HBV)?

Hepatitis B Virus (HBV) is a virus that infects the liver and can cause serious liver disease. If left untreated, this can include liver failure, liver cancer and/or cirrhosis (scarring of the liver). HBV can be short term (acute) or long term (chronic). HBV infection is preventable by a safe and effective vaccine which has been available since the mid-1990s, but different communities are still affected by inadequate vaccine roll out. To date, chronic HBV cannot be cured, but there are safe and effective treatments available that help to fight the virus and slow down damage to the liver.

HBV is transmitted through contact with infected blood or bodily fluids, such as through sexual contact, sharing needles or syringes, or from mother to baby during childbirth. It can also be transmitted through sharing personal items like razors or toothbrushes. It is not transmissible through skin-skin contact (hugs/holding hands), sneezing/coughing, or sharing a meal or drinks with an infected person.


Many people with acute or chronic HBV infection may not have any symptoms, while others may experience symptoms such as fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, clay-colored bowel movements, joint pain, and jaundice (yellowing of the skin and eyes).

About the Evaluation of Vukuzazi LiVEr disease – Hepatitis B Study (EVoLVE)

HBV has a high global burden (~300 million people are living with the infection and it causes close to a million deaths per year), disproportionately affecting African populations. However, there remains a shortage of resources, advocacy, awareness, and limited access to diagnosis and/or treatment pathways. In South Africa (SA) the proportion of the population living with HBV (prevalence) is estimated to be 4.8-5%.

Despite being common in South African populations, there is limited awareness and understanding, and pathways to diagnosis and clinical care are not well developed. Research on HBV is necessary to better understand transmission dynamics, disease progression, HBV drug resistance, and to create and shape public health interventions aimed at reducing HBV transmission. This may include screening programmes, vaccination campaigns, harm reduction strategies for high-risk populations (i.e., people who inject drugs) and education initiatives to raise awareness.


Study overview



EVoLVE uses banked samples, which were collected under the terms of existing ethics for the Vukuzazi programme in KwaZulu-Natal, South Africa. The study is planned across three years, from study start date October 2023 and consists of two phases:

Phase I:

Phase I of the study will make use of existing banked samples from Vukuzazi participants to generate a robust picture of HBV immunity, exposure, and infection in this population; considering age, sex and HIV status. Phase I will also include an engagement with Africa Health Research Institute’s (AHRI’s) Community Advisory Board (CAB) in order to explore community perceptions and knowledge of HBV, and training of clinical staff on the Fibroscan machine, which will be used in phase II to assess liver disease progression in people living with HBV.

CAB engagement

Local beliefs regarding HBV infection and liver disease were sought through AHRI CAB engagements in January 2024 to generate an indigenously contextualised understanding of the HBV landscape. The CAB is an independent advisory group that works in close partnership with AHRI, and has been specifically developed and selected to represent the community, including representatives of different districts and interest groups in the local area. Through this flagship multidisciplinary effort, it was found that there was a significant lack of knowledge regarding HBV within the uMkhanyakude district. HBV was understood more broadly as liver disease, without specific understanding of its cause, modes of transmission, potential outcomes, and approaches to prevention and treatment. HBV is conflated with other causes of liver disease which the community identified to be due to alcohol abuse, ARV use (or misuse), love potions and other traditional medications. HBV in the community was highly stigmatised, and inter-related with traditional beliefs. Financial difficulties and poor quality of life were said to play a role in the lack of access to appropriate health care. After the CAB engagement, the EVoLVE team submitted an ethics amendment to incorporate a further investigation of the mental health and social determinants of disease, coupled with novel HBV testing methodologies.

Above: The EVoLVE – CAB engagement

EVoLVE Fibroscan training

Clinical staff from AHRI, and clinical representatives from surrounding Department of Health hospitals, were invited to attend the training from 24 – 25 January 2024. The FibroScan® (produced by Echosens) is a medical tool used to assess liver stiffness (influenced by inflammation, fibrosis, or scarring), as well as the amount of fat in the liver. It is a non-invasive, painless, ultrasound-based test that helps to evaluate the health of the liver without the need for a liver biopsy. Measuring liver stiffness and fat is particularly useful in monitoring patients with chronic liver diseases such as hepatitis B, hepatitis C, non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease. It provides a way to track changes in liver health over time.

(Above: Fibroscan training)

After having successfully completed Phase I of the study, Phase II commenced in May 2024.

Phase II:

Phase II includes the invitation of selected individuals for clinical review at a  Somkhele clinic. These individuals will be selected based on the data generated in Phase I – in order to develop a detailed picture of liver disease in individuals who have tested positive for HBV infection, and a matched group who are not infected with Hep B. Where possible, viral sequencing will be done to determine molecular characteristics of the virus. Further, EVoLVE will adopt a multidisciplinary approach to inductively explore insights into beliefs, behaviours and barriers to HBV care, and collect preliminary data to inform the relationship between HBV and mental health. This information will help to inform the establishment of a multidisciplinary care pathway for diagnosis, treatment, and prevention of HBV infection in this community.

The EVoLVE study team

The EVoLVE study team is a diverse group of clinicians and scientists, with expertise in infectious diseases, social sciences, laboratory research, public engagement, and data science. We work in collaboration between the Africa Health Research Institute (sites in Durban and Somkhele, South Africa) and The Francis Crick Institute and University College London (in London, United Kingdom). Our project also has links to other HBV research at the University of Stellenbosch (OxSAHEP project) in South Africa, and to HBV studies at KEMRI-Wellcome Trust (STRIKE-HBV project) in Kenya and at the Uganda Virus Research Institute (UVRI) in Uganda.

Relevant papers & resources

Maepa MB, Ely A, Kramvis A, Bloom K, Naidoo K, Simani OE, Maponga TG, Arbuthnot P. Hepatitis B Virus Research in South Africa. Viruses. 2022 Aug 31;14(9):1939. doi: 10.3390/v14091939. PMID: 36146747; PMCID: PMC9503375. https://www.mdpi.com/1999-4915/14/9/1939

Lumley, S. F., Delphin, M., Mokaya, J. F., Tan, C. C., Martyn, E., Anderson, M., … & Matthews, P. C. (2023). A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) genotypic resistance in people treated with entecavir or tenofovir. medRxiv, 2023-11.t/10.1101/2023.11.08.23298154v2 https://www.medrxiv.org/content/10.1101/2023.11.08.23298154v2

Spearman, C. W., Andersson, M. I., Bright, B., Davwar, P. M., Desalegn, H., Guingane, A. N., … & Hepatitis B in Africa Collaborative Network (HEPSANET). (2023). A new approach to prevent, diagnose, and treat hepatitis B in Africa. BMC Global and Public Health1(1), 24. https://bmcglobalpublichealth.biomedcentral.com/articles/10.1186/s44263-023-00026-1

Matthews, Philippa; Anderson, Motswedi; Harling, Guy; Waddilove, Elizabeth; Seeley, Janet; Edwards, Anita; et al. (2024). EVOLVE-HBV Study: Materials to support community dialogue, public engagement and education about Hepatitis B Virus infection in a rural population in KwaZulu Natal, South Africa. figshare. Presentation. https://doi.org/10.6084/m9.figshare.25237756

Matthews, P. C., Beloukas, A., Malik, A., Carlson, J. M., Jooste, P., Ogwu, A., … & Klenerman, P. (2015). Prevalence and characteristics of hepatitis B virus (HBV) coinfection among HIV-positive women in South Africa and Botswana. PLoS One10(7), e0134037. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134037

Matthews, P. C., Jack, K., Wang, S., Abbott, J., Bryce, K., Cheng, B., … & Elsharkawy, A. M. (2022). A call for advocacy and patient voice to eliminate hepatitis B virus infection. The Lancet Gastroenterology & Hepatology7(4), 282-285. https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00475-1/abstract

McNaughton, A. L., D’Arienzo, V., Ansari, M. A., Lumley, S. F., Littlejohn, M., Revill, P., … & Matthews, P. C. (2019). Insights from deep sequencing of the HBV genome—unique, tiny, and misunderstood. Gastroenterology156(2), 384-399. https://www.gastrojournal.org/article/S0016-5085(18)35076-5/fulltext

Martyn, E., Eisen, S., Longley, N., Harris, P., Surey, J., Norman, J., … & Matthews, P. C. (2023). The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda. Elife12, e81070. https://elifesciences.org/articles/81070

Mokaya, J., McNaughton, A. L., Hadley, M. J., Beloukas, A., Geretti, A. M., Goedhals, D., & Matthews, P. C. (2018). A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action. PLoS neglected tropical diseases12(8), e0006629. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006629

Campbell, C., Wang, T., McNaughton, A. L., Barnes, E., & Matthews, P. C. (2021). Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta‐analysis. Journal of viral hepatitis28(3), 493-507. https://onlinelibrary.wiley.com/doi/10.1111/jvh.13452

O’Hara, G. A., McNaughton, A. L., Maponga, T., Jooste, P., Ocama, P., Chilengi, R., … & Matthews, P. C. (2017). Hepatitis B virus infection as a neglected tropical disease. PLoS neglected tropical diseases, 11(10), e0005842. https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005842

Delphin, M., Mohammed, K. S., Downs, L. O., Lumley, S. F., Waddilove, E., Okanda, D., … & Taljaard, J. (2024). Under-representation of the WHO African region in clinical trials of interventions against hepatitis B virus infection. The Lancet Gastroenterology & Hepatology. https://pubmed.ncbi.nlm.nih.gov/38367632/

World Health Organization. (2015). Guidelines for the prevention care and treatment of persons with chronic hepatitis B infection: Mar-15. World Health Organization. https://www.who.int/publications/i/item/9789241549059

World Health Organization.Fact Sheet. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b

Useful links

The Matthews group at The Francis Crick Institute

The Hepatitis B Foundation

The World Hepatitis Alliance

The Hep B community

Contact people

Philippa Matthews (Principal Investigator, EVoLVE): philippa.matthews@crick.ac.uk

Motswedi Anderson (Research Associate, EVoLVE): motswedi.anderson@ahri.org

Janine Upton (Project Manager, EVoLVE): Janine.upton@ahri.org

Gloria Sukali (PhD Student, EVoLVE): gloria.sukali@ahri.org

Elizabeth Waddilove (Laboratory Research Scientist, EVoLVE): elizabeth.waddilove@crick.ac.uk

Marion Delphin (Postdoctoral Researcher, EVoLVE): marion.delphin@crick.ac.uk