A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepatitis C

The effect of ursodeoxycholic acid on liver function tests and on bile acid metabolism was investigated in a multi-center randomized controlled dose study for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600 and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum liver parameters and bile acid composition in the treatment groups were compared with 17 control patients. A similarly significant decrease of serum alanine aminotransferase and serum gamma-glutamyltransferase was observed in patients administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition was determined by high-performance liquid chromatography. At entry, the relative proportions of major bile acids were similar to those observed in normal individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30 mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600 and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic acid increased in a dose-dependent manner, and it was significantly higher than in controls (p0.001). The hydrophobicity index of bile acids was calculated by the method of Heuman, and its correlation with serum parameter levels was analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase decreased in the cases in which hydrophobicity index significantly decreased during treatment. The same correlation was observed between the hydrophobicity index and serum gamma = glutamyltransferase in these two groups. There was no correlation between these parameters in the control and 150-mg groups. There was no correlation between reduction rate of serum alanine aminotransferase and initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)