Age at Establishment of Chronic Hepatitis B Infection as a Risk Factor for Persistent Viral Replication, Liver Fibrosis and Hepatocellular Carcinoma in The Gambia, West Africa

Early age at hepatitis B virus (HBV) infection is known to increase the risk of chronic HBV (CHB) infection. This thesis investigated whether, in addition to increasing the risk of chronicity, early age at HBV infection further increases the risk of hepatocellular carcinoma (HCC) by maintaining high viral replication. A systematic review of observational studies suggested that early age at HBV infection might increase the risk of sequelae of CHB infection. However, there was no data from Africa. A project was therefore designed to explore the effect of age at HBV infection on HCC and its predictors in The Gambia, West Africa, using two proxy variables for the age at infection: birth order and maternal HBV sero-status. A historical cross-sectional study of children born to HBeAg-positive mothers and HBeAg-negative mothers found that having an HBeAg-positive mother is associated with higher risk of positive HBeAg in children. The distribution of birth order was compared between HBV-related HCC cases and HBsAg-positive controls using a historical case-control study and data from the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) project. The former study did not find statistically significant association whilst the latter found an inverse association between birth order and HCC, suggesting that chronic carriers with low birth order might have an increased risk of HCC. Finally, an open community cohort study of HBsAg-positive people in three Gambian villages found that having an HBsAg-positive mother is associated with a number of factors predictive of disease (delayed HBeAg seroclearance, high HBV DNA and alanine transaminase levels over time, active CHB disease, significant liver fibrosis and condition requiring antiviral treatment). These findings suggest that interrupting 6 perinatal mother-to-infant transmission might significantly reduce the burden of liver disease associated with CHB infection in The Gambia.