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在肝损伤和非酒精性脂肪性肝病的背景下,使用传统、靶向和生物性疾病修饰抗风湿药物治疗类风湿关节炎。

Treatment of rheumatoid arthritis with conventional, targeted and biological disease-modifying antirheumatic drugs in the setting of liver injury and non-alcoholic fatty liver disease.

机构信息

Department of Rheumatology and Clinical Immunology, Clinical Hospital Center Rijeka, Faculty of Medicine Rijeka, University of Rijeka, Rijeka, Croatia.

Department of Pharmacology, Clinical Hospital Center Rijeka, Rijeka, Croatia.

出版信息

Rheumatol Int. 2022 Oct;42(10):1665-1679. doi: 10.1007/s00296-022-05143-y. Epub 2022 May 23.

Abstract

Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug-induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs.

摘要

肝脏疾病发病率的增加强调了在开具抗风湿药物时要更加小心,因为这些药物具有肝毒性。已经描述了转氨酶一过性升高至自身免疫性肝炎和急性肝衰竭。在临床试验中,每有 10 例丙氨酸氨基转移酶(ALT)升高,一旦研究药物广泛应用,预计将发生 1 例更严重的肝损伤。生物改善病情抗风湿药物(bDMARDs)和靶向合成(tsDMARDs)不太可能引起肝损伤。然而,已经描述了从转氨酶一过性升高到自身免疫性肝炎和急性肝衰竭等各种表现。非酒精性脂肪性肝病(NAFLD)的研究提供了对预先存在的肝脏疾病的深入了解,这些疾病可能因药物而恶化。糖尿病和肥胖可能是药物性肝损伤(DILI)的额外负担。在炎症和代谢途径的交织中,最重要的细胞因子是 IL-6 和 TNF alpha,它们也是类风湿关节炎生物治疗的基石。本叙述性综述评估了 RA 中 DILI 的复杂性和预防以及涉及生物治疗和 tsDMARDs 的治疗选择。

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