TIMING, SIGNIFICANCE, AND PROGNOSIS OF LATE ACUTE LIVER ALLOGRAFT-REJECTION

Liver allograft rejection is usually divided into acute (cellular) rej ection and chronic (ductopenic) rejection. Most cases of acute rejecti on occur within four weeks of transplantation. There is a paucity of p ublished literature on late acute rejection (LAR) in liver allografts and little is known about factors affecting its occurrence and outcome . To study the predisposing factors, clinical presentation, and progno sis of LAR, data prospectively collected on consecutive adult patients who underwent liver transplantation between 1982 and 1994, were analy zed. LAR was defined as histologically confirmed acute cellular reject ion occurring 30 or more days after liver transplantation. Of the 717 patients, 59 (7.5%) had 71 episodes of LAR. Fifty-seven episodes were seen during the first year after transplantation, the remaining occurr ing between 1 and 6 years. Age, sex, pretransplant diagnosis, donor ma tch of HLA, and blood groups was not associated with risk of LAR. Twen ty-seven (38%) episodes were preceded by subtherapeutic blood levels o f cyclosporine/FK506 (<100 ng/ml and <5 ng/ml, respectively) while an additional 6 (8%) had marginally low blood levels (<150 ng/ml and <10 ng/ml, respectively), Treatment with high-dose prednisolone resulted i n complete resolution of rejection in 36 (51%) episodes, partial respo nse in 21, and no response in 14 patients. Sixteen patients (27%) deve loped chronic rejection and graft loss. Development of chronic rejecti on was not affected by age or sex of the patient, timing of LAR, or hi stological severity of AR. Delayed response to therapy during an earli er episode of AR, and histological findings of centrilobular necrosis or bile duct loss at the time of diagnosis of LAR were associated with high risk of progression to chronic rejection and graft loss.