Intrahepatic cholestasis for 15 years without cirrhosis

Whether prolonged cholestasis is followed by hepatic cirrhosis is still controversial. We have studied two unrelated children who have had cholestasis for 15 years, but neither of whom have developed cirrhosis. Both have severe growth retardation, peculiar facies, pulmonic stenosis, transitory renal tubular acidosis, and vitamin D-resistant rickets. The patients presented in infancy with hepatomegaly and direct hyperbilirubinemia; liver biopsy at that time revealed cholestasis and paucity of bile ducts. Subsequent serial liver biopsies have continued to demonstrate cholestasis, but there has been no evidence of cirrhosis. Electron microscopy has revealed swollen and blunted microvilli of the canalicular membrane of the hepatocyte. The patients have had elevated bile acids in the serum as well as a reversed ration of tri- to dihydroxy bile acids. Treatment with cholestyramine and phenobarbital has brought about symptomatic relief from severe pruritus and excoriation and has lowered the level of serum bile acids, although they are still above the normal range. These findings suggest that cholestasis accompanied by an elevated and reversed bile acid ratio does not universally cause hepatic cirrhosis.