Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy

Scand J Rheumatol. 2002;31(6):330-6. doi: 10.1080/030097402320817040.


Objective: We study liver damage in forty-two patients with rheumatoid arthritis (RA) using light (LM) and electron microscopy (EM) and assess histological changes after four years of treatment with methotrexate (MTX).

Patients and methods: liver biopsies (LB) were taken before and after four years of treatment. Patients received weekly doses of between 7.5-15 mg of MTX.

Results: Fourteen per cent of the baseline LB presented mild perisinusoidal fibrosis (Roenigk IIIA) and the rest a lower Roenigk grade; EM identified an increase in collagen fibers in the Disse spaces in 50% of baseline LB. Neither microscopy technique revealed histological progression in any of the sequential LB. Variables that correlated with histological abnormalities were patient's age, length of evolution of the disease, alcohol consumption and biochemical data (gammaglutamate transferase and albumin); the cumulative dose of MTX was not correlated with worse histological findings. Correlation between the two microscopy techniques was good, though EM was more sensitive than LM for the detection of fibrosis.

Conclusions: RA patients present with liver damage before treatment with MTX. The alterations are mild. At low doses MTX treatment is safe. In addition to the recommendations of the American College of Rheumatology, other factors associated with liver impairment are patient's age and length of evolution of the RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / drug therapy*
  • Biopsy
  • Female
  • Humans
  • Liver / pathology*
  • Liver Diseases / etiology*
  • Liver Diseases / pathology
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Microscopy, Electron
  • Middle Aged
  • Reference Values


  • Antirheumatic Agents
  • Methotrexate