HEPATIC CHOLESTEROL AND BILE-ACID SYNTHESIS IN JAPANESE PATIENTS WITHCHOLESTEROL GALLSTONES

In Japan the composition of gallstones is changing rapidly from the on ce-predominant brown-pigment stones to cholesterol ones. The present w ork was undertaken to clarify the mechanism of cholesterol supersatura ted bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol galls tones, 8 with black- or brown-pigment gallstones, 7 without gallstones ) a liver biopsy and hepatic bile were surgically obtained under stand ardized conditions. The cholesterol saturation of hepatic bile was sig nificantly higher in cholesterol gallstone patients than in gallstone- free controls (195 +/- 10 vs. 146 +/- 8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-C oA) reductase, the rate-limiting enzyme for cholesterol synthesis, cho lesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid s ynthesis, and 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase ( 12 a-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 alpha-hydrox ylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 alp ha-hydroxylase and 12 alpha-hydroxylase activities (Rs = 0.44, P < 0.0 5) in all subjects, irrespective of the existence of gallstones. The a ctivities of the three rate-limiting enzymes did not differ significan tly among the three groups (cholesterol stone, pigment stone and stone -free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gal lstones does not result from an increased hepatic cholesterol synthesi s or a decreased bile acid synthesis.