Dynamic behavior of hepatitis C virus in chronically infected patients receiving liver graft from infected donors

Abstract

We studied the outcome of hepatitis C virus (HCV) infection in 14 patients with end-stage HCV-related liver disease who received HCV-positive liver allografts. Viral sequences specific for donor and recipient were established by direct sequencing of PCR products from the NS5 region and by single-strand conformation polymorphism. Within a few months after transplantation the donor strain took over the recipient strain in 8 patients while in 6 patients it was the recipient strain which ultimately prevailed. Donor and recipient were infected by identical genotypes in 6 donor/recipient pairs and by different genotypes in the remaining 8 pairs. Subtype 1b and type 1 (1a + 1b) became the predominant strains in all recipient/donor pairs in which they were present. Patients retaining their own strain were found to have significantly more active liver disease than those infected by the donor strain. We show that HCV superinfection and overtake phenomena occur in humans and suggest that genotypes 1b and 1 (1a + 1b) may possess replicative advantages over other genotypes. Furthermore, we provide evidence of the existence of interference preventing simultaneous continuous infection even by the same genotype strains. The development of active liver disease associated with recipient strain infection and mild or no disease associated with infection from the donor suggests various pathogenic abilities of different HCV strains.