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Open Access Open Badges Research article

Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes

Emilie Quintin1, Jean-Yves Scoazec2, Hubert Marotte1 and Pierre Miossec1*

Author Affiliations

1 Clinical Immunology Unit, Departments of Immunology and Rheumatology, Edouard Herriot hospital, Place d'Arsonval, 69437 Lyon, France

2 Department of Pathology, Edouard Herriot hospital, Place d'Arsonval, 69437, Lyon, France

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Arthritis Research & Therapy 2010, 12:R143  doi:10.1186/ar3085

Published: 16 July 2010



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.


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.


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.


MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.