580 for CC versus TT). There was no statistically significant difference in overall graft survival according

to recipient IL28B polymorphism (overall 5-year graft survival [n = 118]: 91% versus 76% versus 84% for CC versus CT versus Nutlin 3a TT genotypes [P = 0.2168]). There was also no significant effect of donor IL28B genotype on overall graft survival (5-year graft survival [n = 124]: 79% versus 84% versus 81% for CC versus CT versus TT genotype [P = 0.6977]). Neither recipient nor donor liver IL28B genotype was found to be significantly associated with liver-related mortality at 5 years (P = 0.3956 and P = 0.2418, respectively) (Fig. 2). An analysis was also performed of the association of IL28B genotype with Proteases inhibitor the frequency of a composite endpoint consisting

of: histological evidence of cirrhosis, liver-related death/retransplantation and fibrosis stage ≥2. The analysis was censored for antiviral therapy. This clinical composite endpoint was significantly associated with recipient and donor, IL28B genotype (P = 0.047 and 0.040 for recipient and donor CC versus TT genotypes, respectively) (Fig. 3). This study reports the association between IL28B genotype and virological treatment response and clinical outcome in HCV-infected patients following OLT. This unique cohort allowed interrogation of the respective roles of the IL28B genotype of hepatocytes (donor) and nonparenchymal cells of extrahepatic origin (recipient). We identified important roles for both donor and recipient IL28B genotype in determining treatment outcome. The data also suggest that recipient Dimethyl sulfoxide IL28B genotype may determine the severity of histological recurrence of hepatitis C as indicated by progressive fibrosis. These findings have potentially important implications for the management of HCV following liver transplantation. The frequency of the CC variant in the transplant recipients was significantly lower than that in the non–HCV-infected donor livers. This is consistent with a role for the CC variant in spontaneous clearance of HCV, with enrichment for the non-CC variants in the chronic

hepatitis C population. Indeed, a role for the CC variant in promoting natural clearance has recently been established.6, 7 Patients with the non-CC genotypes are also more likely to be prior nonresponders to IFN-based therapies before proceeding to liver failure and transplantation. IL28B polymorphism, previously associated with treatment response in the nontransplant setting,4, 5, 7, 9, 10 strongly predicted for increased rate of SVR in the current cohort. Recipient and donor IL28B genotype were both independently associated with higher rates of SVR. Compared to the patients with matched recipient:donor non-CC variants, SVR rate was higher in patients with either a donor or recipient CC variant, and highest in patients with matched donor and recipient CC variants.