Transplantation 1995 Nov 27;60(10):1098-103

Timing, significance, and prognosis of late acute liver allograft rejection

Anand AC, Hubscher SG, Gunson BK, McMaster P, Neuberger JM
Liver Unit, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Edgbaston,
Birmingham, United Kingdom

Abstract
Liver allograft rejection is usually divided into acute (cellular) rejection and
chronic (ductopenic) rejection. Most cases of acute rejection occur within four
weeks of transplantation. There is a paucity of published 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 prognosis of LAR, data prospectively collected on
consecutive adult patients who underwent liver transplantation between 1982 and
1994, were analyzed. LAR was defined as histologically confirmed acute cellular
rejection 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 occurring between 1
and 6 years. Age, sex, pretransplant diagnosis, donor match of HLA, and blood
groups was not associated with risk of LAR. Twenty-seven (38%) episodes were
preceded by subtherapeutic blood levels of 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 in complete resolution of rejection in 36 (51%) episodes,
partial response in 21, and no response in 14 patients. Sixteen patients (27%)
developed chronic rejection and graft loss. Development of chronic rejection was
not affected by age or sex of the patient, timing of LAR, or histological
severity of AR. Delayed response to therapy during an earlier 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