Late acute rejection after liver transplantation: the Western Canada experience

Acute rejection usually occurs within 3 months posttransplantation. Most centers reduce immunosuppression over 6 to 12 months to minimize opportunistic infection, malignancy, and drug toxicity. Pretransplant disease and low immunosuppression have been reported in association with late acute rejection (LAR). The objective of this study was to determine the incidence, predictive factors, and outcomes of LAR via retrospective review of adult liver transplant recipients in Western Canada from 1989 to 2000. LAR was defined as biopsy-proven acute rejection occurring more than 180 days posttransplantation. Patient characteristics, immunosuppression, and outcome were determined. Both a univariate and multiple logistic regression analysis were performed. LAR occurred in 97 (23%) of 415 patients more than 180 days posttransplantation. Median follow-up was 402 days (range, 180 to 3137 days); 79% of LAR episodes were graded mild. At the time of LAR, 33% were on a steroid taper. A total of 73% of LAR episodes were treated with pulse intravenous steroids, and 5% were steroid-resistant. In the univariate analysis, patients undergoing transplantation for viral etiologies and older age were associated with less LAR. Immunosuppression was significant in a multiple logistic regression model, but not with a proportional hazards model. On multivariate analysis, only patients undergoing transplantation for viral etiologies remained resistant to LAR (hazard ratio, 0.52; range, 0.34 to 0.93, P = .02). There was a trend toward increased chronic rejection in patients who developed LAR (P = .04). LAR is common and occurs after more than 1 year posttransplantation. Patients undergoing transplantation for viral etiologies seem to have a lower risk of LAR. There may be an increased risk of chronic rejection in those developing LAR.