Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy.
BACKGROUND
Ursodeoxycholic acid is widely used as the standard therapy for the treatment of primary biliary cirrhosis and other cholestatic liver diseases. Although it has been shown to improve biochemical markers and delay disease progression, its effect upon fatigue and pruritus, is at best uncertain.


OBJECTIVE
To assess the safety and efficacy of methotrexate for treating symptomatic primary biliary cirrhosis patients who were biochemical partial responders or non-responders to ursodeoxycholic acid therapy.


METHODS
We treated eight consecutive primary biliary cirrhosis patients with methotrexate who were followed in a single hepatology clinical practice, who were symptomatic, and who had had an incomplete biochemical response to ursodeoxycholic acid therapy. Pruritus and fatigue were assessed at each clinic visit and graded from 0 (asymptomatic) to 4 (incapacitating).


RESULTS
The median dose of methotrexate was 13.75 mg/week (range 7.5-15) and the mean duration of methotrexate therapy was 49 months (range 11-126). At the end of follow-up pruritus in six of seven patients had improved, and fatigue in all patients had improved with the addition of methotrexate therapy (pruritus: baseline 2.9 +/- 1.1 vs. end of treatment 0.6 +/- 1.5, P < or = 0.0175, and fatigue: baseline 3.0 +/- 0.8, vs. end of treatment 1.0 +/- 0.8, P < or = 0.0023). Improvement in symptoms was associated with a significant improvement in biochemical markers of cholestasis. No significant adverse effects of methotrexate were documented.


CONCLUSIONS
Methotrexate should be considered as a potential additive treatment for symptomatic primary biliary cirrhosis patients who are incomplete biochemical responders to ursodeoxycholic acid therapy.
Babatin
M A
MA
Liver Unit, University of Calgary, AB, Canada.
Sanai
F M
FM
Swain
M G
MG
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005221:Fatigue / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011537:Pruritus / Q000188:drug therapy / Q000209:etiology; D012293:Rifampin / Q000627:therapeutic use; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000097:blood
D002756:Cholagogues and Choleretics; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D012293:Rifampin; D008727:Methotrexate