Frequent occurrence of hepatocytic apoptosis in acute rejection of the grafted rat liver.

Abstract

The present study was conducted to examine the histopathological changes of rat liver grafts in the early post-transplantation period. A total of 44 orthotopic liver transplantations were performed using cuff techniques without anastomosis of the hepatic artery. They were divided into four groups: (i) group 1 (syngeneic, Lewis-->Lewis; n = 10); (ii) group 2 (allogeneic, ACI-->Lewis; n = 20); (iii) group 3 (allogeneic with immunosuppression, ACI-->Lewis; n = 12); and (iv) long-surviving grafts (PVG-->Lewis; n = 2). The histological findings were classified into four categories: (i) mild dilatation of Disse's spaces due to ischemia; (ii) bile duct proliferation; (iii) acute rejection; and (iv) zonal necrosis. Bile duct proliferation occurred on day 6 in all three groups and in one of the two long-surviving grafts (120 days). Acute rejection occurred on day 3 and progressed in groups 2 and 3. Zonal necrosis developed in group 2 after day 6, while acute rejection subsided after day 4 in group 3 receiving 15-deoxyspergualin. A few single cell deaths or acidophilic bodies were variably noted. Most of these cells showed signals by in situ nick end-labeling in their nuclei, implying the cells were undergoing apoptosis. The number of apoptotic hepatocytes increased as the progress and decreased with the regression of acute rejection in group 3. Thus, the extent of hepatocytic apoptosis may reflect the magnitude of acute rejection. More frequent distribution of apoptotic hepatocytes in periportal areas suggests that apoptosis may be induced by a variety of pathological stimuli, including the direct cytotoxic effects of lymphocytes, various cytokines and local circulatory disturbances.