Circulating markers for biosynthesis of cholesterol and bile acids are not depressed in asymptomatic gallstone subjects

Cholesterol gallstone disease is often associated with an increased biliary secretion rate of cholesterol, which may be due to abnormalities in hepatic cholesterol metabolism. The aim of the present study was to investigate whether gallstone subjects may have an underlying defect in hepatic cholesterol and bile acid formation.

In 41 asymptomatic gallstone subjects, randomly selected from a population of both sexes 40 and 60 years of age, and in 72 age- and sex-matched controls, plasma levels of lathosterol (reflecting hepatic HMG CoA reductase activity) and 7alpha-hydroxy-4-cholesten-3-one (reflecting cholesterol 7alpha-hydroxylase activity) were analysed. In a subgroup of gallstone subjects and controls, plasma levels of 27-hydroxy cholesterol were also determined.

The gallstone subjects had normal plasma levels of cholesterol but displayed 20-25% higher plasma levels of triglycerides compared with the controls. The plasma level of lathosterol was not significantly different between the two groups of subjects whereas the plasma level of 7alpha-hydroxy-4-cholesten-3-one was about 40% higher in the gallstone subjects compared with the controls. Positive correlations were obtained between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and triglycerides in both groups of subjects. The plasma level of 27-hydroxy cholesterol was similar in gallstone subjects and controls.

The previously reported hypersecretion of cholesterol in gallstone patients is not due to a single metabolic defect leading to increased hepatic synthesis of cholesterol or decreased catabolism of cholesterol to bile acids via 7alpha-hydroxylation or 27-hydroxylation of cholesterol.