title: Ursodeoxycholic acid improves bilirubin but not albumin in primary biliary cirrhosis: further evidence for nonefficacy.
abstract: OBJECTIVE
  In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its effect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs.
  
  
  METHODS
  Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between final mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration.
  
  
  RESULTS
  Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not significantly differ between UDCA- and placebo-treated patients, despite the UDCA effect on serum bilirubin. Therefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients.
  
  
  CONCLUSIONS
  Our findings suggest that UDCA does not alter serum albumin in a way that is consistent with its effect on serum bilirubin. Therefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London NW3 2QG, UK.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Tsochatzis
authors.forename: Maurille
authors.initials: M
authors.lastname: Feudjo
authors.forename: Cristina
authors.initials: C
authors.lastname: Rigamonti
authors.forename: Jiannis
authors.initials: J
authors.lastname: Vlachogiannakos
authors.forename: James R
authors.initials: JR
authors.lastname: Carpenter
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D001663:Bilirubin / Q000097:blood*; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000188:drug therapy*; D008954:Models, Biological; D012709:Serum Albumin / Q000378:metabolism*; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D012709:Serum Albumin; D014580:Ursodeoxycholic Acid; D001663:Bilirubin