Development of ductopaenic liver allograft rejection includes a "hepatitic" phase prior to duct loss

Recent reports suggest the possible role of a parenchymal inflammatory reaction in the developing phase of chronic rejection. The aim of this study was to identify both clinical and histological abnormalities related to the development of chronic rejection, especially the topography of the inflammatory reaction occurring in the post-transplant period.

We studied retrospectively, 103 liver allograft biopsies from 10 patients. These 10 patients represented all the patients who developed chronic rejection (confirmed by duct loss and foamy arteriopathy in these grafts removed at retransplantation) and who had non-viral-related disease originally; in the study period 1990-1998 at the Royal Free Hospital (during which 451 liver transplants were performed). As a control population, we reviewed 28 patients who had been transplanted for non-viral end-stage liver disease at our institution in the same study period and who were retransplanted for complications other than chronic rejection.

In nine patients documented histologically lobular hepatitis preceded chronic rejection. In one patient, although non-specific lobular changes were present in the early post-transplant period, lobular hepatitis was identified repeatedly after chronic rejection had been diagnosed. Cytomegalovirus was identified immunohistochemically in one patient. In the remaining nine patients extensive clinical and histological investigations failed to demonstrate the presence of any known viral agent. Features of hepatitis were found in only 3 of the 28 patients of the control group.

A "hepatitic" phase anticipates chronic ductopaenic rejection. Further studies are necessary in order to clarify the pathogenesis of this reaction.