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Although most studies have not demonstrated decreased patient or graft survival in kidney-alone allograft recipients infected with hepatitis C virus (HCV), the impact of HCV infection on patient and graft survival in HCV-infected kidney-pancreas recipients has not been studied.We undertook a retrospective cohort analysis of 137 kidney-pancreas transplant recipients who were transplanted between January 1989 and May 1996. HCV infection was determined by a positive polymerase chain reaction. Relative risk of death and graft failure was calculated using the Cox proportional hazards model with time-dependent covariates. Relative risks were adjusted (aRR) to control for the number of OKT3-treated rejections and cytomegalovirus status of the recipient at the time of transplantation.Mean length of follow-up was 30.4 months in the HCV-infected patients compared with 31.7 months in noninfected patients. Seven (5.1%) patients were infected with HCV before transplant, one (1%) relapsed after transplantation, and four (2.9%) acquired the infection after transplantation. The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5) increased risk of death after transplant compared with the HCV-negative group, with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was generally the result of liver failure and sepsis, whereas death for those in the uninfected group (n=11) was primarily of cardiovascular origin. Patients infected with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The risk of pancreatic allograft failure was not significantly increased.We conclude that HCV infection in kidney-pancreas transplant patients results in a significantly increased risk of kidney allograft failure and death.