A LONGITUDINAL ANALYSIS OF HEPATITIS-C VIRUS-REPLICATION FOLLOWING LIVER-TRANSPLANTATION

Background & Aims: The pathogenesis of graft injury in liver transplan t recipients with recurrent hepatitis C virus (HCV) infection remains poorly understood, In this study, the relationship between HCV replica tion, genotype, and the evolution of graft damage was investigated, Me thods: HCV RNA was quantified in 184 protocol sera from 25 patients tr ansplanted for HCV cirrhosis, HCV isolates were genotyped, and hepatic expression of core and NS4 antigens was sought in protocol allograft biopsy specimens, Results: Acute lobular hepatitis was accompanied by a steep increase in HCV RNA levels and the appearance of core and NS4 antigens in the graft, Methylprednisolone treatment for acute rejectio n led to a 4-100-fold increase in serum HCV RNA, At the end of follow- up, HCV RNA levels were 3-112 times pretransplant levels and were high er in patients with more severe hepatitis. Progressive liver damage de veloped in 7 of 14 patients with HCV genotype 1b and in 1 of 11 patien ts infected with other genotypes (P = 0.03), Conclusions: Peak viremia levels and the initial detection of HCV antigens in hepatocytes sugge sts increased viral replication at the time of acute HCV hepatitis in the graft, Genotype Ib and higher viremia levels were associated with more severe chronic graft damage.