Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis

Background Ursodeoxycholic acid (UDCA) improves liver function tests and pr olongs survival in primary biliary cirrhosis (PBC), The dose of 10-15 mg/kg /day used in the large trials has largely been based on that used for galls tone dissolution. The only dose-response study of UDCA in PBC suggested tha t a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2 ), Methods Twenty-four biopsy-proven early-stage PBC patients (one male, 23 fe male) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fati gue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe), Liver function tests (LFTs) were performed using conventional meth ods, and serum bile acids were measured using gas liquid chromatography, Results The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDC A between the different doses. There was a trend towards normalization of t he abnormal LFTs in a dose-dependent manner (for gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM ), Multi-factorial analysis showed that UDCA treatment, irrespective of dos e, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using gamma GT and tota l bilirubin as variables, better than 300 mg using ALP and IgM as variables , and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg, Conclusion The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg /day), Eur J Gastroenterol Hepatol 11:1069-1076 (C) 1999 Lippincott William s & Wilkins.