Impact of immunosuppression and acute rejection on recurrence of hepatitis C: results of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.
Whereas the impact of early (first 6 postoperative weeks) acute cellular rejection on patient survival among liver transplant recipients as a whole has been reported to be favorable, we hypothesized treatment for acute cellular rejection may have differing impacts on patient and graft survival in hepatitis C virus (HCV)-infected and HCV-negative transplant recipients. We studied the impact of immunosuppression and rejection on patient and graft survival among the 166 HCV-infected and 602 HCV-negative transplant recipients enrolled onto the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. All data were collected prospectively. The association of early acute cellular rejection with mortality was determined using a Cox proportional hazards model with a time-dependent covariate. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative transplant recipients. HCV-infected transplant recipients experienced similar frequencies of acute cellular and steroid-resistant rejection as patients undergoing liver transplantation for most other indications. The mortality risk was significantly increased (relative risk = 2.4; P =.03) for HCV-infected transplant recipients who developed early acute cellular rejection compared with HCV-negative transplant recipients. None of the HCV-infected transplant recipients developed allograft failure secondary to chronic rejection. The choice of calcineurin inhibitor did not affect posttransplantation outcomes. Early acute cellular rejection occurs at similar frequencies in HCV-infected and HCV-negative transplant recipients. Although an episode of early acute cellular rejection is associated with a lower cumulative mortality among HCV-negative transplant recipients, the opposite is true for HCV-infected transplant recipients, who experience an increased risk for mortality after an episode of early acute cellular rejection. The adverse impact of early acute cellular rejection on patient survival should be considered in developing primary immunosuppression and acute cellular rejection treatment protocols for HCV-infected transplant recipients.