Risk factors for abnormal hepatic enzyme elevation by methotrexate treatment in patients with rheumatoid arthritis: A hospital based-cohort study

Jun Hakamata, Masayuki Hashiguchi, Yuko Kaneko, Kunihiro Yamaoka, Mikiko Shimizu, Junya Maruyama, Tsutomu Takeuchi, Mayumi Mochizuki

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives: Methotrexate (MTX) is used as first-line treatment of rheumatoid arthritis (RA) worldwide. Large interindividual differences in MTX effectiveness and safety occur, and the most frequent adverse reaction is hepatotoxicity, although the main cause remains unknown. We investigated factors associated with MTX-induced hepatic enzyme elevation in a hospital-based cohort study. Methods: Study participants were 114 Japanese adult RA outpatients prescribed MTX. Sixteen types of single-nucleotide polymorphisms were investigated using real-time PCR. Patient characteristics were collected from the electronic medical records. The onset of MTX-induced abnormal hepatic enzyme elevation was defined according to deviation from normal liver enzyme reference values during treatment. The observation period was 1 year after beginning MTX. Associations between MTX-induced hepatic enzyme elevation and patient characteristics were evaluated using the multivariate logistic regression model. Results: Thirty-two patients experienced MTX-induced abnormal hepatic enzyme elevation. In multivariate analysis, MTX dosage, estimated glomerular filtration rate (eGFR), and genetic polymorphisms of ABCB1 3435C>T and ATIC 347C>G were associated with abnormal hepatic enzyme elevation. Conclusions: MTX-induced abnormal hepatic enzyme elevation in Japanese RA patients was associated with dosage and eGFR as nongenetic factors, and with ABCB1 3435C>T and ATIC 347C>G as genetic factors in this hospital-based cohort study.

Original languageEnglish
Pages (from-to)611-620
Number of pages10
JournalModern rheumatology
Volume28
Issue number4
DOIs
Publication statusPublished - 2018 Jul 4

Keywords

  • Abnormal hepatic enzyme elevation
  • allele frequency
  • cohort study
  • methotrexate
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

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