Hepatitis B in Malawi: Epidemiology and determinants of fibrosis and virological expression (360G-Wellcome-109130_Z_15_A)

Hepatitis B (HBV) is highly endemic in Malawi with an estimated seroprevalence of 7.5 (95% confidence interval 5.5-10.6). Among a recently described HIV/HBV co-infected cohort in Blantyre, particularly aggressive virological expression was observed compared to other sub-Saharan African cohorts, with high rates of HBV replication, HBe antigen expression, and poor responses to lamivudine. There are very limited data on the epidemiology and natural history of HBV from sub-Saharan Africa. Current understanding of the environmental, viral and host factors responsible for determination of disease severity are derived largely from Asian and Western cohort studies. The aim of this project is to determine the determinants of severity of HBV among a community study in Blantyre, Malawi. Random adult participants in an observational community-based study of typhoid seroincidence (n=9700) will be screened for HBsAg and 250 positive and 125 negative controls will be recruited. An inpatient cohort of people with liver disease will also be screened for HBV. Markers of HBV virological expression, transient elastography to determine liver fibrosis, questionnaires for lifestyle factors and next generation genome sequencing of HBV and host will be undertaken to determine the relative contribution of environmental, host and viral genetic factors to the development of fibrosis.