Insights into the epidemiology, natural history and pathogenesis of hepatitis C virus infection from studies of infected donors and blood product recipients

Abstract

Studies of patients with post-transfusion non-A, non-B hepatitis and their implicated donors were critical to the discovery of hepatitis C virus (HCV) and to the development and progressive enhancement of HCV immunoassays for donor screening and diagnostic applications. Post-transfusion HCV cases have also been used to define the time course of viral and immunological markers following acute infection. Even more precise data on the timing and characteristics of viremia and immune responses during primary HCV infection have been derived from studies of serial samples from source plasma donors who were identified while in the process of infection and seroconversion. Such data have been critical to the derivation of estimates for the viremic, pre-seroconversion window period, and hence projections of the yield of addition of nucleic acid amplification technology (NAT) or HCV core antigen enzyme immunoassays (Ag-EIAs) to antibody screening in donor and diagnostic settings. In addition to these implications for screening and diagnosis, studies of HCV in the blood donor and blood product recipient settings have yielded substantial insights into the epidemiology, pathogenesis and prognosis of HCV infection. In the future, prospective studies of blood and plasma donors detected in the primary phase of HCV infection by NAT screening, will be important for defining viral and host genetic and immunological determinants of clearance of acute viremia, as well as for investigating the benefits of early treatment. Thus, the findings from studies of HCV among donors and blood product recipients have yielded and should continue to provide important insights into HCV pathogenesis leading to novel diagnostic, therapeutic and vaccination strategies.