Towards elimination of Hepatitis C in Vietnam

Vietnam has a high burden of viral hepatitis. This thesis strives to advance its elimination, addressing important gaps in the literature that I hope will contribute to treatment guidelines and health policy, both in Vietnam and internationally. Firstly, to define the hepatitis epidemic in Vietnam, I assimilate all published seroprevalence data since 1990 to estimate pooled prevalence of HBV, HCV and HDV in high and low risk populations. I show that although blood safety has improved, and HDV is largely confined to high-risk populations, a renewed focus on birth dose HBV vaccination and targeted HCV screening and treatment of people who inject drugs, is urgently required to meet elimination targets. The next chapters address HCV therapy, namely predictive factors for selecting individuals who could be treated for shorter duration, treatment failure in relation to rare HCV subtypes, and the clinical importance of resistance mutations. I describe a prospective clinical trial evaluating the efficacy of shortened sofosbuvir and daclatasvir therapy, based on early virological response: firstly, in genotype 1 or 6-infected individuals with mild disease (chapter 3) and then in genotype 6-infected individuals with advanced liver fibrosis (chapter 4). I show that shortened therapy, with retreatment if needed, can reduce antiviral use while maintaining high cure rates, but that day 2 virologic response alone is not an adequate predictor of cure. I demonstrate that a high frequency of putative NS5A inhibitor resistance mutations in genotype 6 infection does not impact cure rates, negating the need for costly genotyping in Vietnam. In my final data chapter, I explore an innovative means of decentralising HCV care. In two independent study populations from Vietnam and the UK, I show that an increase in routinely taken alanine transaminase after HCV therapy is a reliable screen for treatment failure that could substantially reduce reliance on nucleic acid testing in remote and resource-limited settings.