title: Methotrexate for primary biliary cirrhosis.
abstract: BACKGROUND
  Methotrexate has been used to treat patients with primary biliary cirrhosis as it possesses immunosuppressive properties. The previously prepared version of this review from 2005 showed that methotrexate seemed to significantly increase mortality in patients with primary biliary cirrhosis. Since that last review version, follow-up data of the included trials have been published.
  
  
  OBJECTIVE
  To assess the beneficial and harmful effects of methotrexate for patients with primary biliary cirrhosis.
  
  
  METHODS
  Randomised clinical trials were identified by searching The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE (from their inception until September 2009). Reference lists were also read through. Authors of trials were contacted.
  
  
  METHODS
  We searched to include randomised clinical trials comparing methotrexate with placebo, no intervention, or another drug irrespective of blinding, language, year of publication, or publication status.
  
  
  METHODS
  Our primary outcomes were mortality, and mortality or liver transplantation combined. Dichotomous outcomes were reported as relative risks (RR) and hazard ratios (HR) if applicable. Continuous outcomes were reported as mean differences (MD).
  
  
  RESULTS
  Five trials were included. Four trials with 370 patients compared methotrexate with placebo or no intervention (three trials added an equal dose of ursodeoxycholic acid to the intervention groups). The bias risk of these trials was high. We did not find statistically significant effects of methotrexate on mortality (RR 1.32, 95% CI 0.66 to 2.64), mortality or liver transplantation combined, pruritus, fatigue, liver complications, liver biochemistry, liver histology, or adverse events. The pruritus score (MD - 0.17, 95% CI - 0.25 to - 0.09) was significantly lower in patients receiving methotrexate. The prothrombin time was significantly worsened in patients receiving methotrexate (MD 1.60 s, 95% CI 1.18 to 2.02). One trial with 85 patients compared methotrexate with colchicine. The trial had low risk of bias. Methotrexate, when compared to colchicine, did not significantly effect mortality, fatigue, liver biopsy, or adverse events. Methotrexate significantly benefited pruritus score (MD - 0.68, 95% CI - 1.11 to - 0.25), serum alkaline phosphatases (MD - 0.41 U/l, 95% CI - 0.70 to - 0.12), and plasma immunoglobulin M (MD - 0.47 mg/dl, 95% CI - 0.74 to - 0.20) compared with colchicine. Other outcomes showed no statistical difference.
  
  
  CONCLUSIONS
  Methotrexate had no statistically significant effect on mortality in patients with primary biliary cirrhosis nor the need for liver transplantation. Although methotrexate may benefit other outcomes (pruritus score, serum alkaline phosphatase, immunoglobulin M levels), there is no sufficient evidence to support methotrexate for patients with primary biliary cirrhosis.
authors.affiliation: Department of Gastroenterology, Clinical Hospital Centre Rijeka, Kresimirova 42, Rijeka, Croatia, 51000.
authors.forename: Vanja
authors.initials: V
authors.lastname: Giljaca
authors.forename: Goran
authors.initials: G
authors.lastname: Poropat
authors.forename: Davor
authors.initials: D
authors.lastname: Stimac
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: D003078:Colchicine / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000401:mortality; D016031:Liver Transplantation; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D011537:Pruritus / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic
chemical_list: D005493:Folic Acid Antagonists; D007166:Immunosuppressive Agents; D003078:Colchicine; D008727:Methotrexate