抗氧化剂预防抗结核药物致肝损伤的随机开放研究
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摘要
目的探讨N-乙酰半胱氨酸(NAC)预防抗结核药物肝损伤作用。方法肺结核患者196例,2HRZE/4HR+NAC(A组)及2HRZE/4HR+双环醇(B组)为观察组,2HRZE/4HR为对照组(C组),观察8周内肝损伤情况。结果 (1)A组肝损伤率17.19%,停药率45.5%,低于C组22.73%,53.3%(P=0.691,P=0.430)。B组肝损伤率19.7%,低于C组22.73%(P=0.670),B组停药率76.9%,高于C组53.3%(P=0.778)。A组患者肝损伤率及停药率低于B组(P=0.712,P=0.245)。(2)发生肝损伤时间,A组多见于4~8周,B组多见2周内,C组3个时间段内相同。(3)各组转氨酶高值时间,A组(27.67±23.047)d较B组(19.75±16.080)d及C组(19.93±14.969)d迟。肝功能恢复时间,A组(16.83±9.998)d及C组(16.14±6.982)d较B组(22.10±19.319)d短,(P=0.469,P=0.478)。结论 NAC预防性护肝作用与双环醇相似,但减少治疗中断率及延迟肝损伤发生时间,肝功能恢复时间短。
Objective To explore the role of anti-oxidant acetylcysteine(NAC)in prevention of liver injury induced by anti-tuberculosis drugs. Methods 196 patients were divided into three groups(2 HRZE/4 HR combined with NAC(A),2 HRZE/4 HR combined with bicyclol(B),and 2 HRZE/4 HR(C)and observed for 8 weeks.Results(1)In Group A,rate of incidences of liver injury was 17.19%,medication withdrawal 45.5%,lower than that in group C(22.73% and 53.3%,P = 0.430,P = 0.691). Rate of incidences of liver injury in Group B was 19.7%,lower than group C(22.73%,P = 0.670). Rate of incidences of medication withdrawal in Group B was 76.9%,higher than Group C(53.3%,P = 0.778). Rates of incidence of liver injury and medication withdrawal in group A were lower than Group B,(P = 0.712,P = 0.245).(2)Liver injury occurred in patients mostly in 4 ~8 weeks in Group A,mostly in 2 weeks in Group B,and equally in three time periods in Group C.(3)Transaminase of patients reached high level later in Group A(27.67 ± 23.047)day than Group B(19.75 ± 16.080)day and Group C(19.93 ± 14.969)day. It took shorter time for patients′ liver function to recover in group A(16.83 ±9.998)day and Group C(16.14 ± 6.982)day than that in Group B(22.10 ± 19.319)day. Conclusion Using antituberculosis while giving NAC can decrease the incidence of liver damage,delay the occurrence time of liver injury and reduce the interruption rate of treatment.
Objective To explore the role of anti-oxidant acetylcysteine(NAC)in prevention of liver injury induced by anti-tuberculosis drugs. Methods 196 patients were divided into three groups(2 HRZE/4 HR combined with NAC(A),2 HRZE/4 HR combined with bicyclol(B),and 2 HRZE/4 HR(C)and observed for 8 weeks.Results(1)In Group A,rate of incidences of liver injury was 17.19%,medication withdrawal 45.5%,lower than that in group C(22.73% and 53.3%,P = 0.430,P = 0.691). Rate of incidences of liver injury in Group B was 19.7%,lower than group C(22.73%,P = 0.670). Rate of incidences of medication withdrawal in Group B was 76.9%,higher than Group C(53.3%,P = 0.778). Rates of incidence of liver injury and medication withdrawal in group A were lower than Group B,(P = 0.712,P = 0.245).(2)Liver injury occurred in patients mostly in 4 ~8 weeks in Group A,mostly in 2 weeks in Group B,and equally in three time periods in Group C.(3)Transaminase of patients reached high level later in Group A(27.67 ± 23.047)day than Group B(19.75 ± 16.080)day and Group C(19.93 ± 14.969)day. It took shorter time for patients′ liver function to recover in group A(16.83 ±9.998)day and Group C(16.14 ± 6.982)day than that in Group B(22.10 ± 19.319)day. Conclusion Using antituberculosis while giving NAC can decrease the incidence of liver damage,delay the occurrence time of liver injury and reduce the interruption rate of treatment.
引文
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[14] BANIASADI S,et al. Protective effect of N-acetylcysteine on antituberculosis drug induced hepatotoxicity[J]. Eur J Gastroenterol,2010,22(10):1235-1238.
[15] CHEN Y,YE P,REN C. et al. Pharmacoeconomics of three therapeutic schemes for anti-tuberculosis therapy induced liver injury in China[J]. Open Med(Wars),2018,13:53-63.
[16] EDWIN J W,BRETT A H,YANG Y C,et al.An analysis of Nacetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury[J]. Pharmacol Exp Ther,2012,342(2):529-549.
[17]黄德珍,曾玉兰. N-乙酰半胱氨酸对老年慢性阻塞性肺疾病患者免疫功能及细胞因子的影响[J].实用医学杂志,2015,32(7):1186-1188.
[18] LI S,YANG X,LI W,et al. NAC downregulation of lysyl oxidase activity alleviating bleomycin-induced pulmonary fibrosis inrats[J]. Respiration,2012,84(6):509-517.
[19] VENKETARAMAN V,MILLMAN A,SALMAN M,et al.Glutathione levels and immune responses in tuberculosis patients[J]. Microb Pathog,2008,44(3):255-261.
[2]马玙,卜建玲,陈效友.重视抗结核药物性肝损伤[J].中华结核和呼吸杂,2013,36(10):723-725.
[3]肖和平.抗结核治疗时预防性保肝用药的是与非[J].中华结核和呼吸杂志,2013,36(10):722-723.
[4]王寿明,耿家宝,王敏,等.乙酰半胱氨酸治疗药物性肝损伤疗效观察[J].肝脏,2017,22(1):32-34.
[5]中华人民共和国卫生部.肺结核诊断标准(WS 288-2008)[M].北京:人民卫生出版社,2008.
[6]中华医学会结核病学分会《中华结核和呼吸杂志》编辑委员会.抗结核药所致药物性肝损伤诊断与处理专家建议[J].中华结核和呼吸杂,2013,36(10):732-736.
[7]卜建玲,高微微,谢莉,等.药物性肝损害高危人群抗结核治疗方案的探讨[J].中国防痨杂志,2009,31(2):91-93.
[8]冯婉玉.解读美国胸腔协会对抗结核病治疗产生肝毒性的最新指南[J].国外医药抗生素分册,2007,28(3):135-148.
[9] TOSTMANN A,BOEREE M J,AARNOUTSE R E,et al. Antituberculosis drug-induced hepatotoxicity:Concise up-to-date review[J]. Gastroenterol Hepatol,2008,23(2):192-202.
[10] SODHI C P,RANA S V,MEHTA S K,et al. Study of oxide-tive-stress in isoniazid-rifampicin induced hepatic injury in young rats[J]. Drug Chem Toxicol,1997,20(3):255-269.
[11] CERAMI A. Tumor necrosis factor as a mediator of shock,cachexia and inflammation[J]. Blood Purif,1993,11(2),108-117.
[12] CHALASANI N P,HAYSHI P H,BONKOVSKY H I,et al.ACG Clinical Guideline:The diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol,2014,109(7):950-966.
[13] SAHIN S,ALATAS O. The protective effects of n-acetylcysteine against acute hepatotoxicityTumor necrosis factor as a mediator of shock,cachexia and inflammation[J]. Indina J Gastroenterol,2013,32(5):311-315.
[14] BANIASADI S,et al. Protective effect of N-acetylcysteine on antituberculosis drug induced hepatotoxicity[J]. Eur J Gastroenterol,2010,22(10):1235-1238.
[15] CHEN Y,YE P,REN C. et al. Pharmacoeconomics of three therapeutic schemes for anti-tuberculosis therapy induced liver injury in China[J]. Open Med(Wars),2018,13:53-63.
[16] EDWIN J W,BRETT A H,YANG Y C,et al.An analysis of Nacetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury[J]. Pharmacol Exp Ther,2012,342(2):529-549.
[17]黄德珍,曾玉兰. N-乙酰半胱氨酸对老年慢性阻塞性肺疾病患者免疫功能及细胞因子的影响[J].实用医学杂志,2015,32(7):1186-1188.
[18] LI S,YANG X,LI W,et al. NAC downregulation of lysyl oxidase activity alleviating bleomycin-induced pulmonary fibrosis inrats[J]. Respiration,2012,84(6):509-517.
[19] VENKETARAMAN V,MILLMAN A,SALMAN M,et al.Glutathione levels and immune responses in tuberculosis patients[J]. Microb Pathog,2008,44(3):255-261.