Periportal edema and necrosis as diagnostic histological features of early humoral rejection in ABO-incompatible liver transplantation

Humoral rejection caused by antidonor blood group A/B antibodies is one of the most important obstacles for successful ABO-incompatible liver transplantation. However, no specific morphologic features of liver biopsies to distinguish humoral rejection from other conditions such as ischemia or sepsis have been satisfactorily documented. To histologically clarify the early changes in humoral rejection, we studied 41 cases of living donor ABO-incompatible liver transplantation whose allograft biopsies during the first episode of suspected acute rejection were available within the first postoperative month. Postoperative isohemagglutinin IgM titers were X 64 or more in 21 patients (51%; high-titer group) and less than X 64 in 20 cases (49%; low-titer group). In the high-titer group, elevation of postoperative titers X 64 or more occurred within postoperative days 5.7 +/- 4.1 (range: 1-17). An increase in the incidence of cholangitis was observed in the high-titer group (90% vs. 30%, P <.0001), as well as poorer overall graft survival than in the low-titer group (38% vs. 70%, P <.05). Seven biopsies obtained from the high-titer group within 3 days after the onset of elevation of the antibody titers and one biopsy obtained at the peak of the antibody titers demonstrated periportal edema and necrosis, neither of which was found in the low-titer group. All grafts of these patients caused massive hepatocyte necrosis or severe biliary complications. In conclusion, a high morbidity rate of ABO-incompatible liver transplantation is associated with high postoperative levels of antibody titers. Periportal edema and necrosis observed during elevation of antibody titers can be regarded as histological indications of early changes in severe humoral rejection.