Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes.
BACKGROUND
The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.


METHODS
A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.


RESULTS
Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.


CONCLUSIONS
MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.
Quintin
Emilie
E
Departments of Immunology and Rheumatology, Edouard Herriot hospital, Place d'Arsonval, 69437 Lyon, France. emilie.quintin@yahoo.fr
Scoazec
Jean-Yves
JY
Marotte
Hubert
H
Miossec
Pierre
P
D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D012307:Risk Factors; D000637:Transaminases / Q000097:blood
D018501:Antirheumatic Agents; D015415:Biomarkers; D000637:Transaminases; D008727:Methotrexate