vival, and patient survival. We conclude that HCV geno-Infection with hepatitis C virus (HCV) genotype 1b type 1 and subtype 1b are not associated with disease has been reported to be associated with more severe severity or graft survival in liver transplantation recipiposttransplantation liver disease than infection with ents. (HEPATOLOGY 1996;24:1041-1046.) non-1b genotypes. To address this issue, we evaluated the outcome in 124 patients who underwent liver transplantation for chronic HCV infection. The HCV genotype Chronic hepatitis C virus (HCV) infection is the most comand/or serotype responsible for infection was determon indication for liver transplantation in the United States mined by four different methods. HCV RNA was detected (UNOS database, Detre K, et al, personal communication, in serum samples by polymerase chain reaction (PCR) March 1995). While graft infection, defined as the presence amplification, and quantified by branched DNA assay. of detectable virus, following liver transplantation is nearly Disease severity was expressed as a histological score universal, the severity of recurrent disease is variable. Many (which included grading of portal inflammation, lobular patients with infection have minimal liver damage. When activity, fibrosis, and cytopathic changes). Median duraassessed 1 year after transplantation, approximately 50% of tion of histological follow-up was 25 months (range 1-75 patients with infection have abnormal histology. 1-3 A minormonths). Genotype was assignable in 112 (92.5%) paity of patients (fewer than 5%) develop rapidly progressive tients. Genotypes responsible for infection were as folliver disease following transplantation, culminating in death lows: 1a Γ
32.2%, 1b Γ
27.3%, 2a Γ
7.4%, 2b Γ
8.3%, 3a Γ
or need for retransplantation within the first year. The fac-14%, and mixed infection (more than one subtype) Γ
tors which contribute to the variability in the severity of dis-3.3%. Level of viremia, alanine aminotransferase (ALT), ease posttransplantation are poorly understood, but it has aspartate aminotransferase (AST), bilirubin, and total been suggested that infection with HCV genotype 1b may be histological score were not significantly different in paan important determinant of disease severity. 2,5, Our study tients infected with type 1b compared with patients infocuses on the contribution of viral factors, level of viremia, fected with other genotypes. While duration of histologiand genotype, to the severity of posttransplantation liver discal follow-up was greater in patients infected with type ease. 1b versus other types (P Γ
.02), by univariate and multi-Several studies have focused on the importance of HCV variate analysis neither HCV genotype (1b versus othgenotype in determining severity of disease in the nontransers), level of viremia nor duration of histological followplant setting. Subtype 1b, in contrast to other types, has up were associated with disease severity. Moreover, been reported to be associated with more severe histological there was no significant difference in the actuarial graft disease, a higher risk of hepatocellular carcinoma, and a survival in patients infected with type 1b compared with lower response to interferon treatment. 7-9 A recent U.S. study that of patients infected with non-1b types (82% and 87% has proposed that genotype 1 rather than subtype 1b is preat 3 years, respectively). Reanalysis using HCV genotype dictive of interferon responsiveness. 10 1 showed no association with disease severity, graft sur-In this study, we sought to assess the distribution of HCV genotypes in U.S. liver transplantation recipients, and to examine the independent contribution of genotype and level of Abbreviations: HCV, hepatitis C virus; RT-PCR, reverse transcription-polymerase chain viremia to the severity of posttransplantation liver disease reaction; ALT, alanine aminotransferase; bDNA, branched DNA; RFLP, restriction fragand patient survival.