Possible participation of cholestatic factor in the pathogenesis of intrahepatic cholestasis in alcoholic liver disease.

To elucidate the immunopathogenesis of intrahepatic cholestasis in alcoholic liver disease, the authors investigated the possible participation of a cholestatic factor. The peripheral lymphocytes from patients with intrahepatic cholestasis in alcoholic liver disease were stimulated with ethanol and liver specific lipoprotein in vitro and the culture supernatant was fractionated by gel filtration, using a Sephadex G-75 column. When a definitive fraction (fraction 4) was injected into the mesenteric vein of rats, a marked reduction in bile flow was observed. Similar results were obtained when the blood serum of patients was fractionated in an identical manner and the same fraction was injected into rats via the mesenteric vein. Histologically, dilated bile canaliculi with diminution of microvilli and increased vesicles around the dilated canaliculi were observed by electron microscopy after injection of the active fraction into rats. These results strongly suggest that not only the sensitized lymphocytes produce the cholestatic factor which caused the intrahepatic cholestasis by specific stimulation, but also this factor is involved significantly in the pathogenesis of intrahepatic cholestasis which is observed in patients with intrahepatic cholestasis in alcoholic liver disease.