Acute hepatic allograft rejection: Incidence, risk factors, and impact on outcome †

TLDR

Hepatic allograft rejection is a major post‑transplant complication, with immunosuppressive therapy complications driving morbidity and mortality. The study aimed to assess how histological severity of rejection influences additional immunosuppressive therapy and patient and graft survival. Using the Liver Transplantation Database, the authors examined 762 consecutive adult liver transplant recipients to determine incidence, timing, and risk factors for acute rejection. Among 762 recipients, 64% experienced rejection—mostly within six weeks—, with recipient age, creatinine, AST, edema, HLA‑DR mismatch, cold ischemic time, and donor age independently predicting rejection, and severe histological rejection linked to increased antilymphocyte use and shorter time to death or retransplantation, suggesting that complete elimination of rejection may not be desirable.

Abstract

Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation.