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中国循证儿科杂志

中国循证儿科杂志 ›› 2016, Vol. 11 ›› Issue (4): 309-316.

• 综述 • 上一篇    

抗结核药物致肝毒性易感性研究进展

李颖佳,綦辉,申晨,申阿东   

  1. 首都医科大学附属北京儿童医院、北京市儿科研究所，儿科学国家重点学科，教育部儿科重大疾病研究重点实验室，国家呼吸系统疾病临床医学研究中心，儿童呼吸道感染性疾病研究北京市重点实验室 北京,100045
  • 收稿日期:2016-03-21 修回日期:2016-08-29 出版日期:2016-08-25 发布日期:2016-08-25
  • 通讯作者: 申阿东

Recent progress in susceptibility to antituberculosis drug-induced hepatotoxicity

LI Yin-jia, QI Hui, SHEN Chen, SHEN A-dong   

  1. Children's Hospital, Capital Medical University, Beijing 100045, China
  • Received:2016-03-21 Revised:2016-08-29 Online:2016-08-25 Published:2016-08-25
  • Contact: SHEN A-dong

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摘要：

摘要 抗结核药物常见的药物不良反应（adverse drug reactions，ADR）中，以抗结核药物致肝毒性（antituberculosis drug-induced hepatotoxicity，ATDH）对人体危害最大。常用的一线抗结核药物中，异烟肼（isoniazid，INH）、利福平（rifampicin，RMP）及吡嗪酰胺（pyrazinamide，PZA）均有可能发生ATDH。目前，药物代谢酶（drug metabolism enzyme，DME）和药物转运体的基因多态性与ATDH患病风险的相关性受到较多关注，如I相代谢酶（主要是细胞色素450酶）、II相代谢酶（主要是N-乙酰化转移酶与谷胱甘肽S转移酶）、药物转运体（主要是溶质载体与三磷酸腺苷结合盒）。近年来，抗氧化反应（主要是锰超氧化物歧化酶）和免疫反应（主要是人类白细胞抗原）在ATDH进展中的作用也受到越来越多的关注。此外，如年龄、性别、营养状态、酒精摄入、肝脏基础疾病等非遗传因素，也有可能对ATDH患病风险产生影响。本文就DME、药物转运体、抗氧化反应及免疫反应相关基因的多态性与ATDH患病风险，以及影响ATDH发生的非遗传因素进行综述，旨在提高对ATDH的认识，思考并探讨其未来研究方向。

Abstract:

Abstract Among the common adverse drug reactions (ADR) induced by antituberculosis drugs, antituberculosis drug-induced hepatotoxicity (ATDH) is the most serious ADR. Three common first-line antituberculosis drugs, isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA), may induce ATDH. Investigations on susceptibility to ATDH have so far focused on gene polymorphisms of drug metabolism enzymes (DMEs) and drug transporters, such as phase I metabolizing enzymes (such as the Cytochrome P450 superfamily), phase II metabolizing enzymes (such as N-acetyl transferase 2 and Glutathione S-transferase), and drug transporters (such as Solute carrier and Adenosine triphosphate binding cassette). Recently the role of antioxidant response (such as Manganese superoxide dismutase) and immune response (such as human leukocyte antigen) in the progression of ATDH has also attracted more and more attention. In addition, non-genetic factors, such as age, gender, nutritional status, alcoholism, pre-existing liver disease and other factors, may have an impact on the risk of ATDH. To improve the understanding of ATDH and explore the direction of future research, this review focuses on the relevance between the related gene polymorphisms of DME, drug transporters, antioxidant response, immune response and the risk of ATDH, as well as non-genetic factors influencing the occurrence of ATDH.