The natural history of hepatitis C virus (HCV) infection following liver transplantation and predictors of disease severity remain controversial. The aims of the study were to assess in a homogeneous population of 81 cyclosporinebased HCV-infected liver transplant recipients mostly infected with genotype 1b and undergoing strict protocol annual biopsies: 1) the histological progression of posttransplantation HCV disease and, in particular, the incidence of HCV-related graft cirrhosis within the first 5 years after surgery; and 2) the relationship between progression to cirrhosis and i) rejection episodes and ii) first-year liver biopsy findings. We studied 81 consecutive HCV-RNApositive patients (96% genotype 1b) undergoing liver transplantation between 1991 and 1996 with a minimum histological follow-up of 1 year. All patients received cyclosporinebased immunosuppression and underwent protocol yearly liver biopsies for the first 5 years. The mean histological follow-up was 32 months (range, 12-60 months). Biopsies were scored according to the histological activity index (HAI), with separate evaluation of grade (activity) and stage (fibrosis). Histological hepatitis, present in 97% of patients in the most recent biopsy, was moderate or severe in 64%. Twelve patients developed HCV-related cirrhosis at a median time of 24 months (range, 12-48 months), with an actuarial rate of HCV-cirrhosis of 3.7%, 8.5%, 16%, 28%, and 28% at 1, 2, 3, 4, and 5 years, respectively. Rejection was significantly more common among patients with cirrhosis versus those without (83% vs. 48%; P ‫؍‬ .02), with an association between the incidence of cirrhosis and the number of rejection episodes: 5%, 15%, and 50% in patients without rejection, one and two episodes, respectively (P ‫؍‬ .001). The degree of activity and fibrosis score in the first-year biopsy were higher in patients who developed cirrhosis than in those who did not (P ‫؍‬ .008 and .18, respectively). Cirrhosis related to chronic infection with the hepatitis C virus (HCV) has emerged as one of the leading indications for orthotopic liver transplantation (OLT) worldwide, accounting for 50% of transplantation in Spain.

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To determine whether the presence of hepatitis C virus (HCV) viremia correlates with the severity of liver disease in anti-HCV-positive apparently healthy blood donors, we studied 98 blood donors found positive for anti-HCV using enzyme-linked immunosorbent assay (ELISA). Each subject underwent a liver biopsy, a test for HCV RNA in the serum by polymerase chain reaction (PCR), and a panel of liver injury tests. As a result, 97% of the anti-HCV-positive blood donors had some type of histological abnormality:22 (22%) had minimal changes, 1 (1%) had chronic lobular hepatitis, 40 (41%) had chronic persistent hepatitis (CPH), and 32 (33%) had chronic active hepatitis (CAH). Only 3 subjects had a normal liver histology. HCV RNA was detectable in the serum in 65% of the anti-HCV-positive donors. HCV RNA in serum was detectable in none of the donors with a normal liver histology, in 36% (confidence interval [CI], 17% to 59%) of those with minimal changes, in 70% (CI, 53% to 83%) of those with CPH, and in 87% (CI, 71% to 96%) of those with CAH (P = .00001). HCV RNA was detectable in 75% of the donors with elevated (> 45 U/L) alanine transaminase (ALT) values and in 59% of those with normal ALT levels (P = not significant). The incidence of chronic hepatitis was higher in HCV RNA-positive than in HCV RNA-negative donors (88% vs. 50%; P = .00005).(ABSTRACT TRUNCATED AT 250 WORDS)

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