Abnormal accumulation of endotoxin in biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis

Abstract

Backgrounds/aims: Previous studies have revealed the involvement of Kupffer cells and hepatocytes in the metabolism of endotoxin in the liver. The aim of this study was to investigate the in vivo localization of endotoxin in liver cells, including Kupffer cells, hepatocytes, and biliary epithelial cells, in primary biliary cirrhosis and primary sclerosing cholangitis. We also examined the effect of ursodeoxycholic acid on the intrahepatic distribution of endotoxin in primary biliary cirrhosis.

Methods: The immunohistochemical localization of endotoxin was examined in liver specimens from 30 cases of primary biliary cirrhosis and seven of primary sclerosing cholangitis using a monoclonal antibody against lipid A. Controls were seven cases of obstructive jaundice, ten of hepatitis C virus-related liver cirrhosis, 14 of chronic hepatitis C, and five histologically normal liver cases. Semi-quantitative analysis of endotoxin accumulation was performed to measure the intensity of fluorescence for endotoxin. Nine of the 30 patients with primary biliary cirrhosis underwent a second liver biopsy for evaluation of the ursodeoxycholic acid treatment.

Results: In primary biliary cirrhosis and primary sclerosing cholangitis, biliary epithelial cells showed strong immunostaining for endotoxin as well as hepatocytes and Kupffer cells. Biliary epithelial cells of primary biliary cirrhosis and primary sclerosing cholangitis showed more intense immunoreactivity than those of other controls. In primary biliary cirrhosis, ursodeoxycholic acid reduced the immunoreactivity to endotoxin in biliary epithelial cells, and increased the immunoreactivity to endotoxin in Kupffer cells, but did not affect that in hepatocytes.

Conclusions: Our results revealed that in primary biliary cirrhosis and primary sclerosing cholangitis, endotoxin accumulates abnormally in biliary epithelial cells. In addition, we found that ursodeoxycholic acid treatment in primary biliary cirrhosis may provide a beneficial effect on the intrahepatic metabolism of endotoxin.