The long‐term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis

Abstract

Objective. To determine if the long‐term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA. Methods. Needle biopsies of the liver were performed on a cross‐section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either >3,000 mg or >4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed. Results. Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was >3 times the upper limit of normal. Conclusion. Long‐term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX‐related liver fibrosis and appropriate monitoring guidelines in JRA.

Current Treatment of Juvenile Rheumatoid Arthritis

“…In a study of 14 JRA patients who were treated with methotrexate for a mean of 6.3 years, needle biopsies failed to detect signs of significant liver fibrosis in any of the patients, although some histologic abnormalities were noted. 36 Despite the widespread use of methotrexate, data on immunosuppressive, teratogenic, or oncogenic risks associated with long-term methotrexate therapy in JRA patients are lacking. 29 Current recommendations are not to administer live virus vaccines to patients who are taking methotrexate.…”

Therapeutic advancements in juvenile idiopathic arthritis

“…Preventing these GI side effects may be the most effective way to prevent MTX "intolerance," and hence utilizing daily folic acid and even antinausea medications such as ondansetron may prevent symptoms that can later become conditioned. Mild acute hepatotoxicity can occur and may require dose reduction, but hepatic fibrosis and cirrhosis have not been described in children [31]. Hematologic toxicity manifested as macrocytic anemia, leucopenia, and thrombocytopenia are rare, and reported infections are usually mild common bacterial infections.…”

Juvenile Rheumatoid Arthritis

“…One study in particular investigated the possibility of liver fibrosis. 49 The evidence was . conclusive that although histological changes did occur over time, no significant hepatic damage occurred.…”