Association between donor-recipient HLA-DR compatibility and cytomegalovirus hepatitis and chronic rejection in liver transplantation.

P REVIOUS studies in liver transplant patients have demonstrated that liver allografts matched for HLA. especially HLA-DR, have lower survival rates, raising the concept that HLA plays a dualistic role in liver transplan-tation. HLA matching will reduce rejection but may augment other major histocompatibility complex (MHC) restricted cellular immune mechanisms of liver allograft injury. 1.2 These mechanisms could be related to immune responses, viral infections, and autoimmune disease. Cytomegalovirus (CMV) infection is a major pathogen for transplant patients. The mechanisms of CMV-induced graft injury involve direct viral effects and cell-mediated immune responses. Several in vitro studies have demonstrated that lymphocyte responsiveness to CMV-infected cells is MHC restricted. 3 • 4 Therefore. we postulated that HLA antigen sharing between donor and recipient might influence the development of CMV hepatitis after liver transplantation. In liver transplant patients CMV infection is associated with the development of the vanishing bile duct syndrome, a manifestation of chronic rejection. s Also, the incidence of vanishing bile duct syndrome appears to be higher for liver transplants from donors with HLA-DR matches. 2 This report summarizes our studies on the influence of HLA matching on CMV hepatitis and chronic liver transplant rejection. A more detailed study will be published elsewhere. 6 MATERIALS AND METHODS Study Population and Immunosuppression This study was conducted on 399 adult liver transplant patients who had survived for at least 3 months after surgery. All patients received FK 506 and the protocol of FK 506 treatment is described elsewhere.' Rejection episodes were treated with steroids as a bolus or by tapered doses. Steroid-resistant rejection episodes were treated with OKTI. Serology Complete donor-recipient HLA-A, B, DR, DQ typing was done for 355 liver transplant cases using standard lymphocytotoxicity assays. Pretransplant CMV serological status of donor and recipient was available for 262 transplant cases. Diagnosis of CMV Hepatitis This study focused on CMV hepatitis rather than CMV infection of liver transplant patients. The diagnosis of CMV hepatitis was based on typical inclusion bodies or direct immunoperoxidase detection of CMV early antigen in liver biopsies. Diagnosis of Chronic Rejection Histological criteria for chronic rejection are described elsewhere 8 and include lymphocytic bile duct damage in 50% or more of the portal triads, with evidence of bile duct loss and hepatocanalicular cholestasis.