Necroinflammatory changes in hepatic lobules in primary biliary cirrhosis with less well-defined cholestatic changes

Primary biliary cirrhosis (PBC) is characterized by nonsuppurative inflammation and destruction of interlobular bile ducts. In this study we examined the necroinflammatory changes in hepatic lobules in PBC in the absence of cholestatic changes secondary to bile duct destruction, viral hepatitis types B and C, and progression of histologic stages. Kupffer cell hyperplasia, mononuclear sinusoidal infiltrates, and focal hepatocellular necroses were found frequently in the hepatic lobules. Some cases also showed perivenular zonal necrosis and central to central bridging necrosis. Focal necroses and swollen Kupffer cells were associated with lymphocytes with plump eosinophilic cytoplasm, resembling epithelioid cells. Well-developed and less-defined epithelioid cell granuloma also was occasionally found. The size, number, and distribution of these intralobular necroinflammatory changes varied from case to case and also from lobule to lobule in the same case. beta-2-Microglobulin was expressed on hepatocytes in areas of intralobular necrosis, in association with activated T cells. Laboratory data reflecting necroinflammatory changes in the hepatocytes tended to be elevated in the patients with zonal necroses. It is suggested in this study that necroinflammatory changes in the hepatic lobules are constant and inherent features in PBC and easily recognizable at an earlier histologic stage, and that hepatocytes, in addition to bile duct epithelium, may be targets of the immunologically mediated destruction that characterizes PBC.