Hepatitis C infection: recent insights relevant to transfusion safety

Hepatitis C virus (HCV) infects over 100 million persons worldwide, and is hence one of the most prevalent and clinically significant blood‐borne pathogens. The introduction of HCV antibody screening in the early 1990s led to detection of large numbers of infected donors and dramatic increases in blood safety. The seroprevalence of HCV in blood donors varies, ranging from rates as low as 0·01% in South Africa to ~0·5% in most developed countries, to > 5% in focal endemic areas such as Egypt. Studies of HCV in infected donors and recipients were instrumental in the discovery of HCV, and have yielded ongoing insights into HCV epidemiology, natural history and pathogenesis. Recent examples include detailed characterization of the dynamics of acute HCV infection based on studies of plasma donor panels, and important contributions to understanding viral and host factors influencing HCV transmission and disease outcome based on linked donor‐recipient cohort studies. The addition of nucleic acid testing (NAT) for HCV RNA to routine HCV antibody screening of donors in 1999 further reduced the risk of transfusion‐transmitted HCV. Mini‐pool (MP)‐NAT screening has led to detection of well over 500 donors in the viraemic, preseroconversion phase of primary HCV infection, as well as to discrimination of seropositive donors into those with resolved and chronic infections. Studies of donors with acute, chronic/persistent and resolved HCV infections have further contributed to our understanding of viral and host genetic and immunological determinants of spontaneous clearance of HCV and short‐ and long‐term disease outcomes. This review will highlight these past scientific contributions, and present the results of a recent survey of the yield of HCV MP‐NAT screening and estimated residual risks of MP‐NAT screened transfusions in different regions of the world. Finally, the review will discuss available evidence for the infectivity of very low‐level viraemia that may be missed by MP‐NAT, information that is pivotal to modelling the residual risk of MP‐NAT screened blood transfusions, and which will guide further strategies to reduce risk by further enhancing screening or implementation of pathogen‐inactivation technologies.