Studies on bile acid and bilirubin in liver disease Part 1. Clinical significance of biliary bile acids and three bilirubin fractions in liver diseases

The clinical significance of biliary bile acids and bilirubin concentration in liver diseases was investigated. The relations among bile acids, bilirubins and liver function tests including liver biopsy were studied. The conditions of bile acid measurement by Weber were also criticized. The following results were obtained. 1) Weber's method for bile acid measurements was modified, that is; the concentration of hydrazine hydrate from 3.2% to 5% and NAD from 6.8 mM to 5 mM; then higher extinction coefficients were obtained and the method was adequate for assay of bile acids. 2) The concentration of bile acid correlated with that of bilirubin and of ester-form bilirubin. The molar ratio of glucuronic acid to ester-form bilirubin (MR) correlated with the ratio of glycine conjugated to taurine conjugated bile acid (G/T), with glycocholic acid fraction and with the taurocholic acid fraction. This suggests that the abilities of conjugation of glucuronic acid to bilirubin and of glycine and taurine to bile acid were damaged at similar levels. 3) The ratios of G/T, glycocholic acid to taurocholic acid and glycodihydroxy bile acid to taurodihydroxy bile acid in liver diseases were lower than in healthy subjects. The ratio of trihydroxy bile acid to dihydroxy bile acid (tri/di) in its glycine conjugated form was not significantly altered, but that in taurine conjugated form was elevated in liver diseases, suggesting that the metabolism of bile acid was damaged not only in the glycine conjugated form but also in the taurine conjugated form. The ratio of G/T in the group of cholecystopathy was lower than that of healthy subjects. 4) The ratio of G/T and glycocholic acid fraction correlated with GOT and GPT. The G/T ratio correlated with ZTT and hyppuric acid synthesis test. The low G/T ratio and MR suggested liver cell damage. 5) Many cases with low G/T ratios showed liver cell necrosis and hyperplasia and proliferation of Kupffer cell in liver biopsy specimens. The G/T ratios correlated with the appearance of regeneration of liver cells. These results suggested a significant correlation between the G/T ratio and liver function tests.