title: A randomized trial in primary biliary cirrhosis comparing ursodeoxycholic acid in daily doses of either 10 mg/kg or 20 mg/kg. Dutch Multicentre PBC Study Group.
abstract: BACKGROUND
  Ursodeoxycholic acid (UDCA) prolongs transplantation-free survival in primary biliary cirrhosis (PBC). However, the optimal therapeutic dose has not been established.
  
  
  OBJECTIVE
  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), gamma-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.
authors.affiliation: Department of Hepatogastroenterology, University Hospital Rotterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Van Hoogstraten
authors.forename: M B
authors.initials: MB
authors.lastname: De Smet
authors.forename: W
authors.initials: W
authors.lastname: Renooij
authors.forename: J G
authors.initials: JG
authors.lastname: Breed
authors.forename: L G
authors.initials: LG
authors.lastname: Engels
authors.forename: J W
authors.initials: JW
authors.lastname: Den Ouden-Muller
authors.forename: M C
authors.initials: MC
authors.lastname: Rijk
authors.forename: A M
authors.initials: AM
authors.lastname: Smit
authors.forename: R
authors.initials: R
authors.lastname: Zwertbroek
authors.forename: W C
authors.initials: WC
authors.lastname: Hop
authors.forename: G P
authors.initials: GP
authors.lastname: van Berge Henegouwen
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
authors.forename: H R
authors.initials: HR
authors.lastname: van Buuren
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000032:analysis; D002756:Cholagogues and Choleretics / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid