Improved liver tests and greater biliary enrichment with high dose ursodeoxycholic acid in early stage primary biliary cirrhosis.

BACKGROUND

Ursodeoxycholic acid is currently used for the treatment of primary biliary cirrhosis at 13-15 mg/kg/day, but liver tests of some patients do not return to normal at this dose. Studies reported here were designed to test whether a higher dose of ursodeoxycholic acid than is currently used would induce still greater biliary enrichment of ursodeoxycholic acid and whether such enrichment would lead to still further improvement in liver tests in patients with early primary biliary cirrhosis.

METHODS

A total of 20 patients with histologically proven primary biliary cirrhosis were enrolled. Patients had early stage primary biliary cirrhosis as serum bilirubin levels were normal and the Mayo risk score 4.2 +/- 0.5. Group 1 received 600, 1200 and 1800 mg/day of ursodeoxycholic acid; group 2 received 900, 1500 and 2100 mg/day. The order of periods was randomized. Each treatment period lasted 3 months followed by a further 3 months during which a standard dose of ursodeoxycholic acid was given. At the end of each treatment period, liver tests were evaluated, and biliary bile acid pattern of duodenal bile was determined using high pressure liquid chromatography.

RESULTS

Biliary bile acid became enriched in ursodeoxycholic acid in direct relationship to dosage [r = 0.84, p < 0.001). At doses of 1800 mg/day (25-35 mg/kg/day), biliary ursodeoxycholic acid averaged 69 +/- 6.6%. A progressive decrease of alanine aminotransferase [p < 0.0001), aspartate aminotransferase [p < 0.001) and alkaline phosphatase [p < 0.02) was observed with increasing concentrations of ursodeoxycholic acid in bile. Biochemical liver tests showed a stronger correlation with biliary concentrations of ursodeoxycholic acid than with the administered dose.

CONCLUSIONS

In early primary biliary cirrhosis, higher dose ursodeoxycholic acid appears to be more effective than doses currently recommended.