Bile acids

Observational studies

In a retrospective review of medical records over 12 months, ursodeoxycholic acid (20 mg/kg/day) reduced serum bilirubin concentrations in four of five children with cholestasis and hyperbilirubinemia [ ]. No adverse reactions were reported.

Placebo-controlled studies

In a randomized placebo-controlled study in 219 patients with histology-proven chronic hepatitis (44 HbsAg-positive and 149 anti-HCV antibody-positive) and persistently raised transaminases, oral ursodeoxycholic acid 300 mg bd for 6 months produced significant improvement in clinical and biochemical markers [ ]. Apart from diarrhea, which was reported by a few patients, it was well tolerated.

The combinations of oral ursodeoxycholic acid 13–15 mg/kg/day plus interferon (3 MU three times a week) and interferon plus placebo for 6 months have been compared in a randomized, placebo-controlled study in 91 patients with chronic hepatitis C resistant to interferon [ ]. Combined interferon plus ursodeoxycholic acid was more effective than interferon alone in terms of normalizing alanine transaminase at 6 months (but not at 12 months), but not in terms of viral response. The frequency of adverse reactions was similar in the two groups. Diarrhea, which was reported by a few patients, was the only adverse effect attributable to ursodeoxycholic acid.

The long-term effects of ursodeoxycholic acid 14–16 mg/kg/day has been investigated in a double-blind, placebo-controlled, multicenter trial in 192 patients with primary biliary cirrhosis [ ]. Ursodeoxycholic acid was associated with significant improvement in liver function tests and liver histology, but it did not affect the time to death or liver transplantation. Adverse effects were mild: abdominal pain, flatulence, and diarrhea were reported in nine patients taking ursodeoxycholic acid and six taking placebo.

High-dose ursodeoxycholic acid (20 mg/kg/day) has been compared with placebo in the treatment of primary sclerosing cholangitis in a 2-year double-blind preliminary study in 26 patients [ ]. High-dose ursodeoxycholic acid did not influence symptoms, but resulted in significant improvement in liver biochemistry and a significant reduction in the progression of cholangiographic appearances and liver fibrosis, as assessed by disease staging. No significant adverse effects were reported.

Ursodeoxycholic acid 250 mg tds plus ofloxacin 200 mg bd has been compared with ursodeoxycholic acid alone in the prevention of occlusion of biliary stents in a randomized trial in 52 patients with inoperable obstructive jaundice [ ]. Combination treatment was not superior to ursodeoxycholic acid alone. There was no significant difference in the frequency of adverse events between the two groups.