Mori Shunsuke, Arima Nobuyuki, Ito Masahiro, Ueki Yukitaka, Abe Yasuyo, Aoyagi Kiyoshi, Fujiyama Shigetoshi
Department of Rheumatology, Clinical Research Center for Rheumatic Diseases, National Hospital Organization Kumamoto Saishun Medical Center, Kohshi, Kumamoto.
Department of Pathology, Kumamoto Shinto General Hospital, Kumamoto.
Rheumatol Adv Pract. 2020 Jun 5;4(2):rkaa020. doi: 10.1093/rap/rkaa020. eCollection 2020.
The aims were to determine the incidence rate, predictive factors and severity of liver injury that develops during MTX treatment for RA and to evaluate the role of pretreatment hepatic fat deposition.
We used an ongoing real-life registry containing RA patients who had started MTX between August 2007 and April 2018 at participating institutions. The liver-to-spleen attenuation ratio on CT scans at enrolment was used to evaluate pretreatment fat deposition quantitatively. Patients were followed until persistent transaminitis developed or until the end of the study. Liver biopsy was performed for patients who presented with persistent transaminitis.
We followed 289 new MTX users without pretreatment elevations of transaminases (mean follow-up time, 58.3 months). Hepatic fat deposition was detected in half of the patients at enrolment. During follow-up, persistent transaminitis occurred at a crude incidence rate of 3.13 per 100 person-years, and the cumulative incidence at 5 years was estimated to be 13%. A multivariate Fine-Gray regression analysis showed that the most important predictive factors were pre-existing moderate to severe fat deposition (adjusted hazard ratio, 7.69; 95% CI: 3.10, 19.10) and obesity (adjusted hazard ratio, 2.68; 95% CI: 1.37, 5.25). Non-alcoholic steatohepatitis (NASH) was the most predominant pattern in liver biopsy samples. Hepatic fibrosis was found in 90% of samples, but most cases were not advanced.
Aggravation of underlying fatty liver to NASH with fibrosis seems to be an important mechanism of liver injury that occurs in MTX-treated RA patients.
旨在确定类风湿关节炎（RA）患者接受甲氨蝶呤（MTX）治疗期间肝损伤的发生率、预测因素及严重程度，并评估治疗前肝脏脂肪沉积的作用。
我们使用了一个正在进行的真实世界注册研究，纳入了2007年8月至2018年4月在参与机构开始使用MTX的RA患者。入组时CT扫描的肝脾衰减比用于定量评估治疗前的脂肪沉积。对患者进行随访，直至出现持续性转氨酶升高或研究结束。对出现持续性转氨酶升高的患者进行肝活检。
我们随访了289名治疗前转氨酶未升高的新MTX使用者（平均随访时间58.3个月）。入组时半数患者检测到肝脏脂肪沉积。随访期间，持续性转氨酶升高的粗发病率为每100人年3.13例，5年累计发病率估计为13%。多因素Fine-Gray回归分析显示，最重要的预测因素是既往存在中度至重度脂肪沉积（调整后风险比，7.69；95%CI：3.10,19.10）和肥胖（调整后风险比，2.68；95%CI：1.37,5.25）。非酒精性脂肪性肝炎（NASH）是肝活检样本中最主要的类型。90%的样本中发现肝纤维化，但大多数病例未进展。
潜在脂肪肝加重为伴有纤维化的NASH似乎是MTX治疗的RA患者发生肝损伤的重要机制。
