抗结核药物性肝损害研究进展
Progress in Research on Hepatic Injury Caused by Anti-Tuberculosis Drugs
DOI: 10.12677/acm.2024.1451466, PDF,   
作者: 马勇滔, 张祯祯:重庆医科大学附属儿童医院感染科,重庆
关键词: 抗结核药物药物性肝损害Anti-Tuberculosis Drugs Drug-Induced Liver Injury
摘要: 结核病是⼀种由结核分枝杆菌引起的慢性传染病,目前的结核病治疗主要是采用以一线抗结核治疗药物即异烟肼(Isoniazid, INH [H])、利福平(Rifampin, RIF [R])、吡嗪酰胺(Pyrazinamide, PZA [Z])、乙胺丁醇(Ethambutol, EMB [E])等联合应用为主的方案。异烟肼、利福平、吡嗪酰胺均具有肝脏毒性,联合长时间应用更加大了肝毒性。抗结核药物诱导的肝损伤(drug induced liver injury, DILI)是最重要的不良反应之一,不仅会影响抗结核治疗的方案和进程,还会因为计划外的更改药物或停药,因此导致治疗效果降低和不依从性。本文综述了一线抗结核药物的发生机制、治疗措施等,以加深对抗结核药物性肝损害的认识。
Abstract: Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. Currently, the main treatment for tuberculosis is the combination of first-line anti-tuberculosis drugs, namely isoniazid, rifampin, pyrazinamideand ethambutol. Isoniazid, rifampin, and pyrazinamide all have hepatotoxicity, and their combined long-term use exacerbates liver toxicity. Drug-induced liver injury (DILI) induced by anti-tuberculosis drugs is one of the most important adverse reactions, which not only affects the treatment regimen and progress of tuberculosis but also leads to decreased treatment effectiveness and non-compliance due to unplanned changes in medication or discontinuation. This article reviews the mechanism of action and treatment measures of first-line anti-tuberculosis drugs to deepen understanding of hepatic injury caused by anti-tuberculosis drugs.
文章引用:马勇滔, 张祯祯. 抗结核药物性肝损害研究进展[J]. 临床医学进展, 2024, 14(5): 581-588. https://doi.org/10.12677/acm.2024.1451466

参考文献

[1] World Health Organization (2012) WHO Report 2011 Global Tuberbulosis Report. Global Tuberculosis Report.
[2] Shenje, J., Ifeoma Adimora-Nweke, F., Ross, I.L., et al. (2015) Poor Penetration of Antibiotics into Pericardium in Pericardial Tuberculosis. eBioMedicine, 2, 1640-1649. [Google Scholar] [CrossRef] [PubMed]
[3] Jian, L.I. (2008) Antituberculosis Drug-Induced Hepatotoxicity. Chinese Journal of Gastroenterology and Hepatology, 9, 227-230.
[4] Ostapowicz, G. (2002) Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States. Annals of Internal Medicine, 137, 947-954. [Google Scholar] [CrossRef] [PubMed]
[5] Kumar, R., Shalimar Bhatia, V., et al. (2010) Antituberculosis Therapy-Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome. Hepatology, 51, 1665-1674. [Google Scholar] [CrossRef] [PubMed]
[6] Devarbhavi, H., Dierkhising, R. and Kremers, W.K. (2010) Antituberculosis Therapy Drug-Induced Liver Injury and Acute Liver Failure. Hepatology, 52, 798-799. [Google Scholar] [CrossRef] [PubMed]
[7] Chalasani, N.P., Hayashi, P.H., Bonkovsky, H.L., et al. (2014) ACG Clinical Guideline: The Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. American Journal of Gastroenterology, 109, 950-966. [Google Scholar] [CrossRef] [PubMed]
[8] Fontana, R.J. (2009) Drug-Induced Liver Injury Network (DILIN) Prospective Study. Drug Safety, 32, 55-68. [Google Scholar] [CrossRef] [PubMed]
[9] Jiang, F.R., Yan, H.D., Liang, L.L., et al. (2021) Incidence and Risk Factors of Anti-Tuberculosis Drug Induced Liver Injury (DILI): Large Cohort Study Involving 4652 Chinese Adult Tuberculosis Patients. Liver International, 41, 1565-1575. [Google Scholar] [CrossRef] [PubMed]
[10] Hayashi, P. and Fontana, R. (2014) Clinical Features, Diagnosis, and Natural History of Drug-Induced Liver Injury. Seminars in Liver Disease, 34, 134-144. [Google Scholar] [CrossRef] [PubMed]
[11] Shin, H.K., Kang, M.G., Park, D., et al. (2020) Development of Prediction Models for Drug-Induced Cholestasis, Cirrhosis, Hepatitis, and Steatosis Based on Drug and Drug Metabolite Structures. Frontiers in Pharmacology, 11, Article 67. [Google Scholar] [CrossRef] [PubMed]
[12] 朱蕾, 张建勇. 抗结核药物性肝损害研究进展[J]. 江西医药, 2019, 54(9): 1139-1141.
[13] Verma, A.K., et al. (2015) Isoniazid Prevents Nrf2 Translocation by Inhibiting ERK1 Phosphorylation and Induces Oxidative Stress and Apoptosis. Redox Biology, 6, 80-92. [Google Scholar] [CrossRef] [PubMed]
[14] Ng, C.S., Hasnat, A., Al Maruf, A., et al. (2014) N-acetyltransferase 2 (NAT2) Genotype as a Risk Factor for Development of Drug-Induced Liver Injury Relating to Antituberculosis Drug Treatment in a Mixed-Ethnicity Patient Group. European Journal of Clinical Pharmacology, 70, 1079-1086. [Google Scholar] [CrossRef] [PubMed]
[15] Huang, Y.S., Chern, H.D., Su, W.J., et al. (2003) Cytochrome P450 2E1 Genotype and the Susceptibility to Antituberculosis Drug-Induced Hepatitis. Hepatology, 37, 924-930. [Google Scholar] [CrossRef] [PubMed]
[16] 王骁. 儿童抗结核药物性肝损害回顾性分析[D]: [硕士学位论文]. 重庆: 重庆医科大学, 2019.
[17] Rawat, A., Chaturvedi, S., Singh, A., et al. (2018) Metabolomics Approach Discriminates Toxicity Index of Pyrazinamide and Its Metabolic Products, Pyrazinoic Acid and 5-Hydroxy Pyrazinoic Acid. Human & Experimental Toxicology, 37, 373-389. [Google Scholar] [CrossRef] [PubMed]
[18] Menale, C., Robinson, L.J., Palagano, E., et al. (2019) Absence of Dipeptidyl Peptidase 3 Increases Oxidative Stress and Causes Bone Loss. Journal of Bone and Mineral Research, 34, 2133-2148. [Google Scholar] [CrossRef] [PubMed]
[19] Ahadpour, M., et al. (2015) Mitochondrial Oxidative Stress and Dysfunction Induced by Isoniazid: Study on Isolated Rat Liverand Brain Mitochondria. Drug & Chemical Toxicology, 39, 224-232. [Google Scholar] [CrossRef] [PubMed]
[20] Roy, B., Chowdhury, A., Kundu, S., et al. (2001) Increased Risk of Antituberculosis Drug-Induced Hepatotoxicity in Individuals with Glutathione S-Transferase M1 “Null” Mutation. Journal of Gastroenterology and Hepatology, 16, 1033-1037. [Google Scholar] [CrossRef] [PubMed]
[21] Leiro, V., Fernández-Villar, A., Valverde, D., et al. (2010) Influence of Glutathione S-Transferase M1 and T1 Homozygous Null Mutations on the Risk of Antituberculosis Drug-Induced Hepatotoxicity in a Caucasian Population. Liver International, 28, 835-839. [Google Scholar] [CrossRef] [PubMed]
[22] Yew, W.W., Chang, K.C. and Chan, D.P. (2018). Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity. Antimicrobial Agents and Chemotherapy, 62, e02637-17.[CrossRef
[23] Suvichapanich, S., et al. (2019) Genomewide Association Study Confirming the Association of NAT2 with Susceptibility to Antituberculosis Drug-Induced Liver Injury in Thai Patients. Antimicrobial Agents and Chemotherapy, 63, e02692-18. [Google Scholar] [CrossRef
[24] Askgaard, D.S., Wilcke, T. and Dossing, M. (1995) Hepatotoxicity Caused by the Combined Action of Isoniazid and Rifampicin. Thorax, 50, 213-214. [Google Scholar] [CrossRef] [PubMed]
[25] 张卫平. 内质网应激在利福平诱导的药物性肝损伤中的作用和机制研究[D]: [博士学位论文]. 合肥: 安徽医科大学, 2016.[CrossRef
[26] 吴雪琼, 朱冬林, 张俊仙, 等. 羧酸酯酶基因1多态性鉴定及其与抗结核药物肝毒性相关性研究[J]. 中华内科杂志, 2012, 51(7): 524-530. [Google Scholar] [CrossRef
[27] Zhang, Y., Jiang, Z., Su, Y., et al. (2013) Gene Expression Profiling Reveals Potential Key Pathways Involved in Pyrazinamide-Mediated Hepatotoxicity in Wistar Rats. Journal of Applied Toxicology, 33, 807-819. [Google Scholar] [CrossRef] [PubMed]
[28] Zhang, Y., Guo, H., Hassan, H. M., Su, Y., Song, Y., Wang, T., Sun, L., Zhang, L. and Jiang, Z. (2016). Pyrazinamide Induced Hepatic Injury in Rats through Inhibiting the PPARα Pathway. Journal of Applied Toxicology, 36, 1579-1590.[CrossRef] [PubMed]
[29] Zhang, M., Wang, S., Wilffert, B., et al. (2018) The Association between the NAT2 Genetic Polymorphisms and Risk of DILI during Anti-TB Treatment: A Systematic Review and Meta-Analysis. British Journal of Clinical Pharmacology, 84, 2747-2760. [Google Scholar] [CrossRef] [PubMed]
[30] Chen, R., Wang, J., Tang, S., et al. (2016) Role of Polymorphic Bile Salt Export Pump (BSEP, ABCB11) Transporters in Anti-Tuberculosis Drug-Induced Liver Injury in a Chinese Cohort. Scientific Reports, 6, Article No. 27750. [Google Scholar] [CrossRef] [PubMed]
[31] 郭春平, 何平, 刘小斌. 异甘草酸镁对抗结核药物性肝损害的疗效[J]. 深圳中西医结合杂志, 2020, 30(24): 191-192. [Google Scholar] [CrossRef
[32] 陈向东. 水飞蓟宾胶囊对肺结核患者抗结核药物肝损害的预防作用[J]. 实用中西医结合临床, 2020, 20(10): 59-61.