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抗肿瘤坏死因子-α 制剂与新发肝硬化或非酒精性脂肪性肝病的相关性:一项回顾性队列研究。

Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcoholic fatty liver disease: a retrospective cohort.

机构信息

Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.

出版信息

BMJ Open Gastroenterol. 2020 Apr 15;7(1):e000349. doi: 10.1136/bmjgast-2019-000349. eCollection 2020.

Abstract

OBJECTIVE

Elevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD.

DESIGN

This retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure.

RESULTS

This study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25-1.90).

CONCLUSION

In the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.

摘要

目的

肿瘤坏死因子(TNF)-α 水平升高与肝纤维化进展和非酒精性脂肪性肝病(NAFLD)发病机制有关。本研究旨在探讨抗 TNF-α 药物对肝硬化和 NAFLD 发展的影响。

设计

本回顾性队列研究使用了美国 2010 年 1 月 1 日至 2016 年 12 月 31 日期间的索赔数据库。我们确定了患有强直性脊柱炎、炎症性肠病、银屑病关节炎或类风湿关节炎的成年患者。研究中感兴趣的抗 TNF-α 药物包括阿达木单抗、依那西普、戈利木单抗、英夫利昔单抗和赛妥珠单抗。主要复合结局为新发肝硬化、NAFLD 或非酒精性脂肪性肝炎(NASH)。次要结局为(1)肝硬化和(2)NAFLD 或 NASH 的发生。采用逻辑回归生成抗 TNF-α 药物使用的倾向评分。采用时间依赖性抗 TNF-α 药物暴露的 Cox 比例风险模型调整倾向评分。

结果

本研究共纳入 226555 例免疫相关疾病的新发病例患者。在中位 1.5 年的随访期间,抗 TNF-α 药物治疗与肝脏结局(复合结局 HR:1.47,95%CI 1.27 至 1.70;肝硬化 HR:1.47,95%CI 0.96 至 2.23;NAFLD 或 NASH HR:1.53,95%CI 1.32 至 1.77)风险增加相关。每种免疫相关疾病的复合结局风险均增加(HR 1.25-1.90)。

结论

短期内,我们未观察到抗 TNF-α 药物治疗对免疫相关疾病患者肝硬化、NAFLD 或 NASH 发展有益。

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