The metabolism of cholestanol in primary biliary cirrhosis

The concentration of serum cholestanol, a 5α-saturated derivative of cholesterol, is increased in primary biliary cirrhosis proportionally to impaired liver function for unknown reasons. The purpose of this study was to analyze serum cholestanol level and its biliary and fecal elimination, and relate the results to cholesterol absorption and metabolism. Methods: Sixteen patients with primary biliary cirrhosis and 44 non-primary biliary cirrhosis controls were studied. Squalene and non-cholesterol sterols were analyzed by gas-liquid chromatography, cholesterol absorption by the peroral double-isotope continuous feeding method, and neutral and acidic sterols in bile and feces by gas-liquid chromatography. Results: In primary biliary cirrhosis, the mean level of serum cholesterol was normal, but the cholestanol/cholesterol proportion was increased 4-fold, and the proportion was related to the serum bile acid and bilirubin levels. The mean biliary cholestanol proportion and the biliary secretion rate were increased 5- and 2-fold, respectively, suggesting that at low cholestanol absorption cholestanol synthesis was increased. Calculated clearance of serum cholestanol into bile was decreased. The fecal output was within the control limits, so that intestinal cholestanol production was lowered in primary biliary cirrhosis. In addition, serum and biliary plant sterol proportions were increased in primary biliary cirrhosis, but their biliary secretion was unchanged, while those of cholesterol, bile acids, phospholipids, and cholesterol precursor sterols were markedly reduced. Conclusions: We conclude that an enhanced cholestanol synthesis and a cholestasis-induced decrease in biliary clearance of serum cholestanol contribute to the excessively high serum cholestanol level in primary biliary cirrhosis. In addition, reduced bile acid synthesis may contribute to the increased serum cholestanol content.