Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis.
OBJECTIVE
To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX).


METHODS
We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case-control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease.


RESULTS
Twenty-four cases of cirrhosis and liver failure were identified, giving a 5-year cumulative incidence of approximately 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease.


CONCLUSIONS
Serious liver disease is an uncommon, age- and dose-related complication of low-dose MTX therapy for RA.
Walker
A M
AM
Epidemiology Resources Inc., Newton Lower Falls, MA 02162-1450.
Funch
D
D
Dreyer
N A
NA
Tolman
K G
KG
Kremer
J M
JM
Alarcón
G S
GS
Lee
R G
RG
Weinblatt
M E
ME
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000139:chemically induced*; D017093:Liver Failure / Q000139:chemically induced*; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
D008727:Methotrexate