PERSISTENT HEPATITIS-C VIRUS-INFECTION AFTER LIVER-TRANSPLANTATION - CLINICAL AND VIROLOGICAL FEATURES

We report a prospective clinical and virological study of 18 patients undergoing orthotopic liver transplantation, selected because of hepat itis C virus (HCV) RNA positivity before transplantation. Nine of the 18 patients (50%) developed chronic active hepatitis (CAH) in liver al lografts during the first year posttransplantation; hepatitis was firs t observed between 6 and 25 weeks posttransplantation HCV viremia was measured for all patients before transplantation and on posttransplant ation days 3, 7, and 14, and months 1, 6, 12, and 24 to 41, by quantit ative competitive RNA polymerase chain reaction (QC-PCR). HCV RNA leve ls on posttransplantation days 3, 7, and 14 were significantly higher among patients who subsequently developed CAH versus those who did not (P < .02 by t-test and Mann-Whitney test on all three dates). However , HCV RNA levels in sera obtained at 1, 6, and 12 months posttransplan tation did not correlate with CAH at 1 year or with HCV genotype deter mined in posttransplantation sera. At least two serial liver biopsy sp ecimens from each patient were stained for HCV nonstructural 4 (NS4) a ntigen by immunohistochemistry. The intensity of cytoplasmic staining of NS4 antigen was significantly higher for specimens with CAH versus those without CAH (P = .028 by chi(2)). Three patients developed bridg ing fibrosis in liver allografts during the first year after transplan tation; all three patients had intense (3+) immunostaining for NS4 ant igen, and the infecting genotypes were 1a, 1b, and 1a plus 1b, respect ively. In summary, the 18 patients all developed high-titer viremia by 1 month after Liver transplantation, whereas CAH developed in 50% of allografts during the first year after transplantation. Patients with recurrent CAH were characterized by higher HCV RNA titers during the f irst 2 weeks posttransplantation and increased staining of HCV NS4 ant igen in diseased liver biopsy specimens; however, the role of virologi cal factors in the recurrence of CAH after liver transplantation remai ns uncertain.