Unexpected Maintenance of Hepatitis C Viral Diversity following Liver Transplantation

Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis in up to 20 % of individuals, often requiring liver transplan-tation. Although the new liver is known to be rapidly reinfected, the dynamics and source of the reinfecting virus(es) are unclear, resulting in some confusion concerning the relationship between clinical outcome and viral characteristics. To clarify the dy-namics of liver reinfection, longitudinal serum viral samples from 10 transplant patients were studied. Part of the E1/E2 region was sequenced, and advanced phylogenetic analysis methods were used in a multiparameter analysis to determine the history and ancestry of reinfecting lineages. Our results demonstrated the complexity of HCV evolutionary dynamics after liver trans-plantation, in which a large diverse population of viruses is transmitted andmaintained for months to years. As many as 30 inde-pendent lineages in a single patient were found to reinfect the new liver. Several later posttransplant lineages were more closely related to older pretransplant viruses than to viruses detected immediately after transplantation. Although our data are consis-tent with a number of interpretations, the persistence of high viral genetic variation over long periods of time requires an activ