Cholesterol and bile acid metabolism in moderately advanced, stable cirrhosis of the liver

Bile acid and lipid metabolism were studied in a metabolic ward in 8 patients with moderately advanced, but stable alcoholic cirrhosis, and in 17 control subjects of comparable age and weight. Patients with biopsy-proved cirrhosis were well nourished and had neither ascites nor encephalopathy. Routine liver function tests were normal apart from elevated gamma-glutamyl transpeptidase and significant BSP retention. However, concentrations of serum bile acids and excretion of urinary bile acids were elevated. Their pool sizes and hepatic secretion rates of bile acids were somewhat reduced, but not markedly so, as reported for patients with far-advanced cirrhosis. Also, in contrast to patients with more advanced cirrhosis, our patients did not show a marked reduction of either cholate or deoxycholate in the bile acid pool. Despite relatively low pools of bile acids, percent saturation of fasting gallbladder bile with cholesterol and hepatic secretion of cholesterol were similar to those of control subjects; this lack of an increased saturation in cirrhotics appeared to be due to a greater coupling of cholesterol to phospholipids and bile acids at low outputs of bile acids than found in normal subjects. Cholesterol absorption measured by a combined intestinal perfusion-sterol balance technique was comparable in the two groups. When the cirrhotic subjects were treated with cholestyramine (16 g/day) for 1 mo, they were able to increase their bile acid synthesis from 4.5 ± 1.6 to 19.8 ± 10.9 mg/kg/day, and this increase was comparable to 3 control subjects similarly tested. In addition, in both groups of subjects, cholic acid became the major bile acid in the pool (70 ± 5% in cirrhotic and 71 ± 8% in controls). Serum cholesterol fell to similar levels in both groups. These findings indicate that patients with moderately advanced, compensated cirrhosis do not have marked disturbance of cholesterol and bile acid metabolism that has been found in patients with advanced, decompensated cirrhosis. However, mild changes in biliary lipid metabolism anticipate those found in more severe cirrhosis.