A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg

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Abstract
Background: Ursodeoxycholic acid (UDCA) prolongs transplantation‐free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established.Aim: To compare the effects of UDCA administered in daily doses of 10 vs. 20 mg/kg on symptoms, liver biochemistry and biliary UDCA enrichment.Methods: A 6‐month multicentre randomized open controlled trial was conducted to assess the effects of an increase in the dose of UDCA to 20 mg/kg/day vs. continuation of 10 mg/kg/day for patients who had not achieved biochemical normalization during treatment for at least 6 months with the 10 mg/kg dose. Clinical and laboratory evaluations were performed at entry and at 3‐month intervals. The percentage UDCA in duodenal bile was assessed at entry and at 6 months.Results: Sixty‐one patients were enrolled. No side‐effects of UDCA were observed. Within the 20 mg/kg/day group significant decreases were found for alkaline phosphatase (− 8%; P = 0.003), aspartate aminotransferase (− 11%; P = 0.01), alanine aminotransferase (− 17%; P < 0.001), γ‐glutamyl transferase␣(− 34%; P < 0.001), immunoglobulin M (− 11%; P = 0.002) and cholesterol (− 8.1%; P < 0.001). In the 10 mg/kg group none of these parameters differed significantly from baseline. No significant differences between dose groups for symptom scores or serum bilirubin were found. Biliary enrichment with UDCA increased from 37% to 46% in the 20 mg/kg group (P = 0.02) while remaining stable in the 10 mg/kg group.Conclusions: Liver biochemistry improved in PBC patients receiving UDCA 20 mg/kg/day compared to a dose of 10 mg/kg/day. Both doses were equally well tolerated. These results indicate that UDCA 10 mg/kg/day is a suboptimal dose for treating PBC.