Ursodeoxycholic acid for chronic liver diseases

Different bile acids have different effects on liver cells, depending on the degree of hydroxylation of the bile acid and the orientation of hydroxy groups. In decreasing order of hydrophobicity, and therefore hepatotoxicity, the bile acids may be ranked as follows: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. The rationale for the use of ursodeoxycholic acid in chronic liver disease is to increase the overall hydrophilicity of the bile acid pool, which, because of cholestasis, retains potentially hepatotoxic bile acids. Recent clinical studies have indicated that ursodeoxycholic acid improves liver function indices in patients with primary biliary cirrhosis and chronic hepatitis at doses ranging between 10 and 15 mg/kg/day. These doses would be considered in the high range in the use of ursodeoxycholic acid for gallstone dissolution. In a preliminary study we found that also lower doses were effective in primary biliary cirrhosis. Two studies to determine the optimal dose of ursodeoxycholic acid for chronic hepatitis and anicteric primary biliary cirrhosis were then carried out. Eighteen patients with primary biliary cirrhosis and 12 patients with chronic hepatitis were treated with 250, 500, and 750 mg of ursodeoxycholic acid per day for three consecutive 2-month periods. Highly significant decreases in serum enzyme levels were seen with the 250 mg/day dose, which were further improved by the higher doses. The improvement roughly paralleled the enrichment of conjugated bile acids with ursodeoxycholic acid. A separate study investigating the effect of shifting the bile acid pool composition toward less detergent moieties was also done.(ABSTRACT TRUNCATED AT 250 WORDS)