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Hepatotoxicity in patients with juvenile idiopathic arthritis receiving longterm methotrexate therapy
Pekka Lahdenne1, Juhani Rapola, Heikki Ylijoki
1Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. pekka.lahdenne@hus.fi
Objective:
To evaluate hepatotoxicity in patients with juvenile idiopathic arthritis (JIA) receiving methotrexate (MTX) therapy with doses of 20-30 mg/m2 of body surface area.
Methods:
We graded the histology of percutaneous liver biopsies from 34 patients with JIA receiving longterm (> 2.4 years) MTX therapy at the Rheumatism Foundation Hospital, Heinola, Finland, using the Roenigk classification scale. Medical records of the patients with JIA were retrospectively analyzed.
Results:
Of 10 patients with MTX doses >/= 20 mg/m2, 4 had grade II, 5 had grade I histology, and one specimen with extensive steatosis as the only pathologic finding could not be classified. All 24 patients treated with low dose MTX had grade I histology. No specimen showed fibrosis or cirrhosis. In 2 patients with grade II histology, extensive portal tract inflammation resolved when MTX was discontinued for 6 months.
Conclusion:
Aggressive medical treatment of JIA with MTX at 20-30 mg/m2 with concomitant disease modifying antirheumatic drugs and corticosteroids may contribute to minor liver abnormalities that seem to be reversible.
Insights
Methotrexate (MTX) therapy for juvenile idiopathic arthritis (JIA) at high doses may cause reversible liver changes. Liver histology showed minor abnormalities, with no fibrosis or cirrhosis observed in patients.
Area of Science:
- Rheumatology
- Hepatology
- Pediatric Rheumatology
Background:
- Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease.
- Methotrexate (MTX) is a common disease-modifying antirheumatic drug (DMARD) used in JIA treatment.
- Potential hepatotoxicity of MTX necessitates careful monitoring.
Purpose of the Study:
- To evaluate liver histology in JIA patients treated with MTX at doses of 20-30 mg/m2.
- To assess the severity and reversibility of MTX-induced liver abnormalities.
Main Methods:
- Retrospective analysis of liver biopsy histology in 34 JIA patients.
- Grading of liver histology using the Roenigk classification scale.
- Correlation of histology with MTX dosage and treatment duration (> 2.4 years).
Main Results:
- Higher MTX doses (>/= 20 mg/m2) were associated with grade I or II histology in 9 out of 10 patients.
- One patient with high-dose MTX showed steatosis as the sole abnormality.
- All patients on lower MTX doses had grade I histology; no fibrosis or cirrhosis was observed.
- Grade II histology resolved after MTX discontinuation in two patients.
Conclusions:
- Aggressive MTX therapy (20-30 mg/m2) for JIA may lead to minor, reversible liver abnormalities.
- Concomitant use of DMARDs and corticosteroids might influence liver findings.
- Liver histology in JIA patients on MTX generally shows mild changes without progression to fibrosis or cirrhosis.