Cholic acid synthesis as an index of the severity of liver disease in man

Abstract

SUMMARY Bile acid pool size and kinetics were determined in 17 patients with cirrhosis and 11 patients without liver disease and correlated with the severity of liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points) cirrhosis. The clinical rating was then correlated with the various aspects of bile acid metabolism. Cholic acid synthesis was markedly reduced in the early stages of cirrhosis and continued to decrease with the advancement of the liver disease. There was an inverse correlation between synthesis of cholic acid and the severity of cirrhosis. Nine of the 10 patients with advanced cirrhosis and a very low cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild cirrhosis also had significantly reduced cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast, chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of cholic acid and the severity of liver disease. The fractional daily turnover rate of cholic acid was greatly reduced (50%) in patients with advanced cirrhosis. Deoxycholic acid was reduced in patients with mild cirrhosis and virtually absent from the bile of patients with advanced cirrhosis. The findings of the present report provide evidence that cholic acid synthesis is a sensitive indicator of the hepatocellular damage, whereas chenodeoxycholic acid synthesis is relatively unaffected by cirrhosis. The selective alteration in cholic acid synthesis probably resides in a deficiency of one or more enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of cholic acid.

Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.

“…Precursor studies in humans indicate that the acidic pathway synthesizes ‫ف‬ 50% of the total bile acids (14). In adult patients with liver diseases, when bile acid synthesis is reduced (54)(55)(56)(57), concentrations of cholestenoic acids are elevated (58), which also suggests that the alternative pathway is a significant contributor to bile acid synthesis in humans.…”

Glucagon and glucose tolerance in liver cirrhosis

“…Patients with cirrhosis were graded according to a clinical scoring system and all 10 were evaluated as having 'advanced' cirrhosis (McCormick et al 1973) ( Table 1).…”

The metabolism of steroids in the fatty liver induced by orotic acid feeding

“…However, probably because of a defective 12a-hydroxylase, the formation of cholic acid is subnormal, whereas the synthesis of chenodeoxycholic acid tends to be correspondingly increased (Einarsson et al, 1975). With increasing degree of liver cirrhosis, the formation of cholic acid decreases gradually (Vlahcevic et al, 1972;McCormic et al, 1973).…”