Chronic rejection after liver transplantation: a study of clinical, histopathological and immunological features

In an effort to better understand chronic liver transplant rejection, we studied 110 children and adults who survived for at least 2 mo after the transplant procedure. Chronic rejection was defined using a combination of clinical and histopathological criteria and was diagnosed in 10 of the 110 patients for an incidence of 9.1%. All 10 patients were children with the mean age 3.4 yr vs. 21.7 yr for patients without chronic rejection (p less than .001). Males and females were equally represented, and nine received a liver from a gender-matched donor. Four patients were non-Caucasian, resulting in an incidence of 21.7% in non-Caucasian recipients vs. 6.6% in Caucasian recipients (p less than .05). All chronic rejection patients received a liver from an ABO-compatible donor. T-cell crossmatch was negative in all patients in whom it was assessed, and no significant disparity in either the class I or class II human leukocyte antigen loci was noted. Patients who had chronic rejection experienced acute rejection earlier, 11 days vs. 16 days (p less than .05), than patients who did not. In 8 of 10 patients, chronic rejection appeared to evolve directly from early episodes of acute rejection that were unresponsive to immunosuppressive therapy. Two distinct histological presentations were noted. One was progressive loss of bile ducts without hepatocellular injury (four patients), and the other was characterized by worsening ischemic hepatocellular damage and fibrosis (six patients) in addition to severe ductular injury. The first was associated with a more benign clinical course, the second with rapidly deteriorating hepatic function. Three patients recovered spontaneously 9 to 14 mo after transplant, one died awaiting a donor for retransplant, and five had retransplants. We conclude that chronic rejection after the operation is a relatively uncommon complication of liver transplantation with a variable clinical course and unpredictable outcome.