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 > deoxycholic > chenodeoxycholic > cholic > 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-months 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. For this purpose, 24 patients with chronic hepatitis were randomly assigned to two of the following four treatment: ursodeoxycholic acid (600 mg/day), taurine (1.5 g/day), ursodeoxycholic acid + taurine (600 mg + 1.5 g/day), and placebo, administered for two successive cycles of 2 months each. Ursodeoxycholic acid, but not placebo or taurine, significantly improved liver function indices. The addition of taurine to ursodeoxycholic acid did not induce any further change, despite a significant increase in tauroconjugates in biliary bile acids. The results of these and other studies conducted to date suggest that ursodeoxycholic acid is a potentially useful therapeutic agent for chronic liver disease. Long-term controlled studies should be done, utilizing doses of ursodeoxycholic acid of 500-600 mg/day.
|Journal||Journal of Clinical Gastroenterology|
|Issue number||SUPPL. 2|
|Publication status||Published - 1988|
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