Hepatitis B Virus (HBV)
Why is this virus a problem?
Estimates suggest that 260-290 million people worldwide have chronic hepatitis B virus (HBV) infection, accounting for substantial morbidity and mortality. Particularly in populations where HIV infection is also endemic, there is evidence of an emerging burden of chronic liver disease, and rates of liver cancer are climbing worldwide. The urgent need to tackle this problem is recognised by the United Nations Sustainable Development Goals, which set out the ambitious challenge of eliminating the public health threat of HBV by the year 2030.
Although there is a safe and effective vaccine against hepatitis B, the virus continues to be transmitted due to the large population reservoir of chronic infection, incomplete vaccination coverage, ongoing mother-to-child transmission, vaccine escape mutants, and failure of some individuals to mount an adequate immune response. There is a range of antiviral drugs that can be used to suppress the virus, but there come with a potential risk of drug-resistance, and even successful therapy must be taken life-long in most cases.
Although HBV affects 10-fold more people than HIV worldwide, it has been neglected by research, and by clinical and public health services, leading to poor awareness and education, stigma and discrimination, and a lack of robust data on which to base interventions. Many parts of Africa are particularly vulnerable to these problems.
What are we doing about it?
Our research group at the University of Oxford, led by Dr Philippa Matthews, is working on diverse challenges that must be tackled if we are to meet the 2030 target.
Our projects focus on different aspects of HBV infection and transmission, with the following aims:
- Filling in gaps in our understanding of epidemiology and transmission, through careful assessment of individual clinical cohorts and a systematic analysis of pan-Africa data;
- Developing a better understanding of which patients are at most risk of long-term liver disease, and identifying characteristics associated with suppression or natural clearance of the virus.
- Using biomarkers to better monitor disease progression or clearance;
- Recognising and tackling stigma associated with HBV infection, and working with patients to understand their individual experiences.
- Defining relevant polymorphisms in the viral genetic code that are associated with escape from drugs, vaccines or the host immune response;
- Assessing progress that has been made through vaccination programmes, and projecting the extent to which the 2030 target can be met, using a combination of clinical data, cost effectiveness analysis and mathematical modelling.
A member of the team working on viral sequencing at the Medawar Building, Oxford
Our vision is to enhance advocacy for HBV, leading to better recognition, education and funding of both clinical and research infrastructure. Through understanding behaviour, providing education and striving to develop political advocacy, we hope to be able to influence better access to diagnosis and treatment.
By pursuing a robust understanding of host and viral correlates of control and clearance, we can advance patient-stratified care and ultimately help to inform the design of curative therapies.
We are strong supporters of data sharing, and ensure our work is available on pre-print servers (such as BioRxiv) ahead of peer-reviewed publication whenever possible.
We work closely with patients, healthcare workers and the public to engage in wide discussions about the nature and impact of our work; you can find examples of our projects and links to key outputs on our 'Viral Footprints' website.
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| HBV word cloud created to publicise World Hepatitis Day | Click here to read the article about our group's work, reporting the story of one of our patients from Uganda |
COLLABORATORS
We work in partnership with other groups studying viral hepatitis based in Oxford, including Prof Ellie Barnes, Prof Jane McKeating and Prof Paul Klenerman. We have developed close links with Dr Jose Lourenco and Prof Sunetra Gupta to work on mathematical modelling of HBV infection.
Our clinical cohorts in South Africa are a result of productive collaborations with clinical and research teams at the University of Stellenbosch (co-ordinated by Dr Tongai Maponga) and the University of the Free State (co-ordinated by Dr Nickie Goedhals).
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| Members of the study team at Tygerberg Hospital, Cape Town (University of Stellenbosch) | Members of the study team at Bloemfontein University Hospital, Bloemfontein (University of the Free State) |
We have recently developed links with the MRC General Population Cohort in Uganda (Prof Rob Newton and Prof Janet Seeley).
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Tygerberg Hospital, Cape Town (site of University of Stellenbosch collaboration) |
Road to the Uganda Virus Research Institute, Entebbe, Uganda |
A partership with the Wellcome Trust for Human Genetics has underpinned the development of a pipeline for next generation sequencing of HBV (working with Dr David Bonsall, Dr Mariateresa deCesare, Dr Rory Bowden) and we are working with the Modernising Medical Microbiology group (led by Prof Derrick Crook) to develop diagnostic sequencing tools, focusing on a range of different viruses.
Through a partnership with the NIHR Health Informatics Collaborative ('HIC'), we are developing better routes to accessing 'Big Data' from routine clinical laboratories, with the long-term goal of collating anonymised data from centres across the UK to drive quality improvement and answer clinical research questions.
Group members at the international liver meeting, hosted by the European Association for the Study of the Liver (EASL)
FUNDERS
This work is funded by a Wellcome Trust Intermediate Fellowship. I have also received research grants from the Rosetrees Trust, University of Oxford John Fell Fund, MRC Global Challenges Research Fund, and British Infection Association.
Diagnostic viral sequencing work is funded by the Oxford BRC.
SOME KEY PUBLICATIONS
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A Study of Knowledge, Experience, and Beliefs About Hepatitis B Virus (HBV) Infection in South Western Uganda. Mugisha J, Mokaya J, Bukenya D, Ssembajja F, Mayambala D, Newton R, Matthews PC, Seeley J. Front Public Health. 2019;7:304. doi: 10.3389/fpubh.2019.00304
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Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus (HBV) infection in South Africa. Mokaya J, Burn EAO, Tamandjou CR, Goedhals D, Barnes EJ, Andersson M, Pinedo-Villanueva R, Matthews PC. BMC Public Health. 2019;19(1):829. doi: 10.1186/s12889-019-7095-4.
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Electronic Health Informatics Data To Describe Clearance Dynamics of Hepatitis B Surface Antigen (HBsAg) and e Antigen (HBeAg) in Chronic Hepatitis B Virus Infection. Downs LO, Smith DA, Lumley SF, Patel M, McNaughton AL, Mokaya J, Ansari MA, Salih H, Várnai KA, Freeman O, Cripps S, Phillips J, Collier J, Woods K, Channon K, Davies J, Barnes E, Jeffery K, Matthews PC. MBio. 2019 Jun 25;10(3). pii: e00699-19. doi: 10.1128/mBio.00699-19.
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Illumina and Nanopore methods for whole genome sequencing of hepatitis B virus (HBV). McNaughton AL, Roberts HE, Bonsall D, de Cesare M, Mokaya J, Lumley SF, Golubchik T, Piazza P, Martin JB, de Lara C, Brown A, Ansari MA, Bowden R, Barnes E, Matthews PC. Sci Rep. 2019 May 8;9(1):7081. doi: 10.1038/s41598-019-43524-9.
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FAIR data needed to liberate hepatitis B virus (HBV) from the catch-22 of neglect. Matthews PC. J Glob Health. 2019 Jun;9(1):010310. doi: 10.7189/jogh.09-010310
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HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model. McNaughton AL, Lourenço J, Hattingh L, Adland E, Daniels S, Van Zyl A, Akiror CS, Wareing S, Jeffery K, Ansari MA, Klenerman P, Goulder PJR, Gupta S, Jooste P, Matthews PC. BMC Med. 2019 Feb 21;17(1):43. doi: 10.1186/s12916-019-1269-x.
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A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action. Mokaya J, et al., PLoS Negl Trop Dis. 2018 Aug 6;12(8):e0006629. doi: 10.1371/journal.pntd.0006629.
- A blind spot? Confronting the stigma of hepatitis B virus (HBV) infection - A systematic review. Mokaya et al. Wellcome Open Res 2018, 3:29 (doi: 10.12688/wellcomeopenres.14273.2)
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Hepatitis B Virus Adaptation to the CD8+ T Cell Response: Consequences for Host and Pathogen. Lumley S et al, Front Immunol. 2018 Jul 16;9:1561. doi: 10.3389/fimmu.2018.01561.
- Hepatitis B virus as a neglected tropical disease. O'Hara et al. PLoS Negl Trop Dis. 2017 Oct 5;11(10):e0005842. doi: 10.1371/journal.pntd.0005842.
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Hepatitis B vaccine shortage: another symptom of chronic neglect? Matthews PC, Barnes E. BMJ. 2017 Oct 19;359:j4686. doi: 10.1136/bmj.j4686.
- Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. Matthews PC et al, J Clin Virol. 2014 Sep;61(1):20-33. doi: 10.1016/j.jcv.2014.05.018. Review.
- Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana. Matthews PC et al PLoS One. 2015 Jul 28;10(7):e0134037. doi: 10.1371/journal.pone.0134037.
- HLA-A is a Predictor of Hepatitis B e Antigen Status in HIV-Positive African Adults. Matthews PC, et al., J Infect Dis. 2016;15;213(8):1248-52. doi: 10.1093/infdis/jiv592.
- Screening, characterisation and prevention of Hepatitis B virus (HBV) co-infection in HIV-positive children in South Africa. Jooste P, et al. J Clin Virol. 2016;85:71-74. doi: 10.1016/j.jcv.2016.10.017.
- Hepitopes: A live interactive database of HLA class I epitopes in hepatitis B virus. Lumley S, et al., Wellcome Open Res. 2016 Nov 15;1:9.
...for more on HBV, as well as other
infections of crucial relevance to global
health, my illustrated textbook was
published by Oxford University Press in
July 2017
