摘要:
甲氨蝶呤(MTX)是治療類風濕性關節炎的一線藥物。在甲氨蝶呤的療效和安全性存在很大的個體差異，而最常見的不良反應是肝毒性，但肝損傷的主要原因仍然不明。我們以醫院為基礎的隊列研究，分析甲氨蝶呤導致肝酶升高的影響因素。
方法：研究對象為服用甲氨蝶呤的114名日本成人RA門診患者。采用實時熒光定量PCR法檢測了15種單核苷酸多態性。從電子病曆中收集患者信息。在使用MTX治療過程中肝酶偏離正常參考值定義為MTX誘導的肝酶升高。觀察期為MTX開始後1年。用多變量logistic回歸模型評估MTX誘導肝酶升高與患者各個臨床因素之間的聯係。
結果：32例患者出現MTX引起的肝酶異常升高。在多變量分析中，MTX的劑量、估算的腎小球濾過率、ABCB1 3435C>T和 ATIC 347C>G基因多態性與MTX誘導的肝酶異常升高有關。
結論：在這個以醫院為基礎的隊列研究中提示，日本RA患者MTX誘導的肝酶升高不但與MTX劑量和EGFR等非遺傳因素有關，而且與ABCB1 3435C>T和 ATIC 347C>G遺傳因素也相關。
附原文：
OBJECTIVES: Methotrexate (MTX) is used as first-linetreatment of rheumatoid arthritis (RA) worldwide. Large inter individualdifferences in MTX effectiveness and safety occur, and the most frequentadverse reaction is hepatotoxicity, although the main cause remains unknown. Weinvestigated factors associated with MTX-induced hepatic enzyme elevation in ahospital-based cohort study. METHODS:Study participants were 114 Japanese adult RA outpatients prescribed MTX.Fifteen types of single-nucleotide polymorphisms were investigated usingreal-time PCR. Patient characteristics were collected from the electronicmedical records. The onset of MTX-induced abnormal hepatic enzyme elevation wasdefined according to deviation from normal liver enzyme reference values duringtreatment. The observation period was 1 year after beginning MTX. Associationsbetween MTX-induced hepatic enzyme elevation and patient characteristics wereevaluated using the multivariate logistic regression model. RESULTS: Thirty-twopatients experienced MTX-induced abnormal hepatic enzyme elevation. Inmultivariate analysis, MTX dosage, estimated glomerular filtration rate (eGFR),and genetic polymorphisms of ABCB1 3435C>T and ATIC 347C>G were associated with abnormal hepatic enzymeelevation. CONCLUSIONS:MTX-induced abnormal hepatic enzyme elevation inJapanese RA patients was associated with dosage and eGFR as non-geneticfactors, and with ABCB1 3435C>T and ATIC 347C>G as genetic factors in this hospital-based cohortstudy.
引自：Hakamata J,Hashiguchi M, Kaneko Y, et al. Risk factors for abnormal hepatic enzymeelevation by methotrexate treatment in patients with rheumatoid arthritis: ahospital based-cohort study[J]. Modern Rheumatology, 2017:1-27.
