Hepatitis C virus: risk factors and disease progression

Hepatitis C virus (HCV) is a single-stranded RNA virus and was first identified in 1989 as a cause for transfusion-associated non-A, non-B hepatitis. Transmission of HCV occurs predominantly via blood-to-blood contact. After acute infection about 75% of those infected progress to a persistent infection and become at risk for liver cirrhosis, end-stage liver disease, or hepatocellular carcinoma (HCC). In contrast to hepatitis B virus (HBV), there is no effective vaccine against HCV. Over the past two decades HCV treatment has rapidly improved and new direct acting antiviral agents (DAA) will further improve its effectiveness and tolerability.
The studies in this thesis were performed to improve our understanding of the risk, the natural history, and the long-term complications of HCV infection for PWID and HIV-infected MSM. Investigation of acute HCV infection can provide valuable insights into HCV pathogenesis, which could benefit vaccine design and treatment improvement. Development of successful preventive strategies is dependent on knowledge of factors that drive HCV transmission, especially with respect to marginalized populations such as PWID. Acute infection is usually asymptomatic and therefore rarely recognized. Importantly, longitudinal follow-up of HCV seroconverters provides insight into the full course of disease progression and HCV-associated morbidity and mortality. This might help improve treatment decision making.