HISTOLOGICAL AND ULTRASTRUCTURAL APPEARANCE OF THE LIVER DURING GRAFT-VERSUS-HOST DISEASE COMPLICATING BONE MARROW TRANSPLANTATION

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Abstract
Liver lesions are some of the manifestations of graft-versus-host disease (GVHD), a major complication of bone marrow transplantation. These disorders are probably attributable to the cytopathogenic reaction of immunocompetent donor cells on host liver target cells. The aims of this study were (1) to describe the liver lesions occurring during GVHD and (2) to look for those pathological features illustrating the action of immunocompetent cells. Fourteen patients with GVHD were studied; six patients had an acute form and eight had a chronic form of GVHD. In all patients, hepatomegaly, jaundice, and high alkaline phosphatase levels were noted. Light and electron microscopic examination showed lesions of similar nature but of various degrees in both forms of GVHD. Three pathological changes were remarkable. Two of them seemed to reflect the cytopathogenic effect of lymphocytes: (1) some hepatocytes were necrotic, with frequent close membrane contacts between lymphocytes and hepatocytes and (2) portal bile duct cells were necrotic, also with close contacts between biliary cells and lymphocytes. The third remarkable change was the presence of numerous and voluminous Kupffer cells, probably reflecting the macrophage hyperactivity known to occur in the disease. If necrosis of hepatocytes and biliary cells seem to be, at least in part, directly related to the cytopathogenic effect of lymphocytes, however it cannot be decided from this purely morphological study whether the other lesions observed, such as intra-hepatocytic cholestasis, steatosis, hepatosiderosis and portal fibrosis, are directly related to the immune disorders induced by bone marrow transplantation.