3种用药方案治疗HIV/TB患者抗结核药物性肝损伤成本-效果分析

目的探讨3种不同治疗方案用于治疗HIV/TB患者抗结核药物性肝损的经济效果。方法将168例患者随机分成3组,A组还原型谷胱甘肽序贯、B组复方甘草酸苷序贯,C组还原型谷胱甘肽静滴序贯复方甘草酸苷口服,观察疗效和不良反应。结果 3种药物治疗方案成本分别为1221元、1076.5元、960.7元;发生不良反应率分别为50%、41.1%、44.6%(P>0.05);成本-效果比分别为12.91、12.83、10.55;有效率分别为94.6%、83.8%、91.1%(P<0.05);三种方案治疗HIV/TB患者抗结核药物性肝损在有效率上无显著差异,在A、B两组肝功能上(总胆红素)有显著差异。结论还原型谷胱甘肽静滴序贯复方甘草酸苷口服方案为较佳方案。     

复方甘草酸苷治疗抗结核药物性肝炎的临床疗效分析

目的观察复方甘草酸苷治疗抗结核药物性肝炎的临床疗效。方法将65例由应用抗结核药物所引起的药物性肝损伤患者随机分为治疗组和对照组,治疗组给予复方甘草酸苷(复方甘草酸苷注射液60 ml加5%葡萄糖注射液250 ml,静脉滴注,每日1次)治疗4周,对照组给予还原型谷胱甘肽(还原型谷胱甘肽1.2 g加入5%葡萄糖注射液250 ml中静脉滴注,每日1次)治疗4周,对两组进行疗效比较。结果治疗组在肝功能恢复,症状、体征的改善方面差异均有显著性(P0.05)。结论复方甘草酸苷治疗药物性肝炎疗效可靠,值得临床推广。     

复方甘草酸苷联合还原型谷胱甘肽治疗抗结核药物性肝损害57例疗效观察

目的观察复方甘草酸苷联合还原型谷胱甘肽治疗抗结核药物引起药物性肝损伤中的护肝作用。方法抗结核药物引起药物性肝损伤57例,随机分成治疗组32例与观察组25例,治疗组采用复方甘草酸苷联合还原型谷胱甘肽治疗。观察组采用肝太乐,门冬氨酸钾镁治疗。疗程3周,治疗后监测肝功能情况。结果疗程结束后治疗组在肝功能指标ALT、AST、TBIL方面明显优于观察组（P〈0．001）。结论复方甘草酸苷联合还原型谷胱甘肽在治疗抗结核药物引起药物性肝损伤中有显著护肝作用。     

保肝药对AIDS合并TB病人抗结核治疗中药物性肝损伤的预防效果分析

目的了解艾滋病(AIDS)病人使用保肝药物,对标化四联抗结核(TB)治疗中药物性肝损伤的预防效果。方法回顾性分析采用标化四联抗结核治疗的AIDS合并TB的住院病人(简称AIDS/TB病人),对强化期内使用保肝药物预防(治疗组)与未使用保肝药物预防(对照组)的病人,比较两者药物性肝损伤的发生率。预防使用的保肝药为还原型谷胱甘肽或复方甘草酸苷。有3种以上肝损伤危险因素同时存在的病人,称为肝损伤高危病人。结果符合条件的211例病例中,治疗组122例,肝损伤发生率为13.1%(16例);对照组89例,肝损伤发生率为19.1%(17例);两组比较肝损伤发生率差异无统计学意义(χ2=1.398、P0.05)。肝损伤高危病人134例,使用保肝药物的86例,肝损伤发生率15.1%(13例),未使用保肝药物的48例,肝损伤发生率为25.0%(12例),两组比较无统计学意义(χ2=1.983、P0.05)。使用复方甘草酸苷65例,肝损伤发生率为13.8%(9例),使用还原型谷胱甘肽57例,肝损伤发生率为12.3%(7例),两组比较差异无统计学意义(χ2=0.001、P0.05)。结论 AIDS/TB病人使用保肝药物预防抗结核药肝损伤效果不显著,需灵活掌握治疗方案。     

复方甘草酸苷治疗抗结核药物性肝损害的疗效分析

目的分析复方甘草酸苷治疗抗结核药物性肝损害的临床疗效。方法 115例抗结核药物性肝损害患者随机分为两组,对照组(n=55)在常规抗结核药物治疗基础上加用还原型谷胱甘肽治疗,观察组(n=60)在常规抗结核药物治疗基础上加用复方甘草酸苷治疗。两组疗程均为2周,观察治疗前后两组患者治疗总有效率及肝功能指标(ALT、AST和TBIL)改善情况。结果观察组治疗总有效率(83.3%)明显高于对照组(69.1%)(P0.05);治疗后观察组患者肝功能指标(ALT、AST和TBIL)改善情况明显优于对照组(P0.05)。结论复方甘草酸苷治疗抗结核药物性肝损害安全有效。     

复方甘草酸苷治疗抗结核药引起的药物性肝炎临床观察

目的观察复方甘草酸苷治疗抗结核药药物性肝炎的临床疗效。方法将48例抗结核药引起的药物性肝炎患者随机分成治疗组27例和对照组21例。治疗组给予复方甘草酸苷治疗4周,对照组给予还原型谷胱甘肽治疗4周,观察治疗前后血生化指标的变化。结果治疗组患者的肝功能改善情况优于对照组(P<0.05)。结论复方甘草酸苷有较好的保肝、降酶作用,未见不良反应。     

复方甘草酸苷联合还原型谷胱甘肽治疗酒精性肝硬化的疗效观察

目的 评价复方甘草酸苷联合还原型谷胱甘肽在治疗酒精性肝硬化中的临床疗效.方法 选取咸宁市中心医院收治的酒精性肝硬化患者120例作为研究对象,随机分为复方甘草酸苷组、还原型谷胱甘肽组及联合用药组.复方甘草酸苷组患者每天给予120 mg复方甘草酸苷进行治疗;还原型谷胱甘肽组患者每天给予1.8g还原型谷胱甘肽进行治疗;联合用药组患者每天给予120 mg复方甘草酸苷＋1.8 g还原型谷胱甘肽进行治疗;治疗周期均为20 d.结果 与单独用药组相比,联合用药组能显著改善患者各临床症状（P＜0.05）,患者经联合用药治疗后,GGT、AST、ALT、TBIL水平降低幅度显著高于单独用药组（P＜0.05）;复方甘草酸苷组总有效率为62.5％,还原型谷胱甘肽组总有效率为65.0％,联合用药组总有效率为92.5％,联合用药组治疗效果显著优于单独用药组（P＜0.05）.结论 复方甘草酸苷联合还原型谷胱甘肽对酒精性肝硬化的治疗效果显著优于单独用药,值得临床推广应用.     

还原型谷胱甘肽、甘草酸二铵和复方甘草酸苷治疗抗结核药物所致药物性肝损伤患者成本-效益分析

目的 探讨应用还原型谷胱甘肽、甘草酸二铵氯化钠和复方甘草酸苷注射液治疗抗结核药物所致的药物性肝损伤(DILI)患者的成本-效益。方法 2018年2月～2021年6月我院收治的93例抗结核药物所致的DILI患者被随机分为A组、B组和C组,每组31例,分别给予还原型谷胱甘肽注射液、甘草酸二铵氯化钠注射液或复方甘草酸苷注射液治疗4周。分别采用黄嘌呤氧化法、硫代巴比妥酸法和二硫基双硝基苯甲酸法检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)水平,采用ELISA法检测血清白细胞介素-6(IL-6)、IL-1β和肿瘤坏死因子-α(TNF-α)水平。结果 在治疗4周结束时,三组血生化指标无显著性差异(P>0.05);A组血清SOD、MDA和GSH-Px水平分别为(79.1±10.2)U/L、(5.4±0.9)μmol/L和(112.3±14.6)U/L,与B组【分别为(78.3±7.9)U/L、(6.2±1.5)μmol/L和(106.8±17.1)U/L】或C组【分别为(77.7±11.4)U/L、(5.9±1.1)μmol/L和(109.6±12.9)...     

3种常用改善肝功能药物治疗药物性肝损伤的效果比较

目的对比3种常用改善肝功能药物治疗药物性肝损伤的效果。方法回顾性分析2012年11月~(-2)015年4月于应城市人民医院治疗的90例药物性肝损伤患者的临床资料,根据治疗用药的不同,分为A、B、C 3组,每组30例。其中A组采用还原型谷胱甘肽治疗,B组采用多烯磷脂酰胆碱注射液治疗,C组患者采用硫普罗宁注射液治疗。对比3组患者治疗效果、药物成本以及不良反应发生率。计量资料多组间比采用方差分析,进一步两两比较采用LSD-t检验;计数资料多组间比较采用χ~2检验。结果A组总有效率为90.0%,明显高于B组(73.3%)和C组(76.7%),差异均有统计学意义(χ~2值分别为2.78、3.75,P值均0.05)。B组药物成本为(316.12±4.05)元,明显高于A组(235.13±2.90)元和C组(135.21±7.62)元,差异均有统计学意义(P值均0.01)。3组不良反应发生率比较差异无统计学意义(P0.05)。结论在药物性肝损伤的临床治疗中,还原型谷胱甘肽较多烯磷脂酰胆碱、硫普罗宁所获效果更为显著,同时成本费用也比较合理,可优先选用该药治疗。     

艾滋病合并结核病患者抗结核治疗中肝损伤情况调查

目的 了解艾滋病合并结核病(HIV/TB)患者在标准化抗结核治疗中肝损伤的发生情况及对预后的影响.方法 对361例HIV/TB患者在抗结核治疗最初2月内(强化期)肝损伤发生率、程度、预后情况进行总结,并随机抽取382例抗HIV阴性结核病患者做对照.结果 HIV/TB组肝损伤总发生率为40.2％,严重肝损伤发生率为10.8％,因肝损伤更改抗结核方案为14.4％,治疗失败率为7.8％;HIV阴性组肝损伤总发生率为21.7％、严重肝损伤率为4.5％、更改抗结核方案者为5.2％、治疗失败率为0.8％,两组比较有统计学意义.结论 AIDS/TB患者抗结核治疗中易发生肝损伤,严重肝损伤患者增多,需更改治疗方案.     

HIV／TB患者治疗过程中抗结核药物性肝损伤的临床分析

目的 判断和比较HIV阳性和阴性的结核患者抗结核药物诱导肝毒性（antituberculosis drug—induced hepatotonicity，ATDH）的临床特征。方法收集资料完整的临床病例75例HIV阳性、63例阴性的结核患者，监测ATDH的发生率和临床特征。结果 亚临床ATDH发生率为12．3％（17／138）．临床ATDH发生率为6．5％（9／138），与HIV阳性、CD4细胞计数降低、联合用药有关。结论 HIV患者免疫状态低下时，ATDH是HIV相关TB患者的一个重要问题，应常规监测肝功能和早期发现临床症状。     

3种用药方案治疗下呼吸道感染的成本-效果分析

目的探讨3种不同治疗方案用于下呼吸道感染的经济效果。方法运用药物经济学成本-效果分析法对A组(左氧氟沙星口服)、B组(阿奇霉素口服)、C组(左氧氟沙星 阿奇霉素口服)进行回顾性分析评价。结果3种药物治疗方案成本分别为34.8元、56元、59.3元;细菌清除率分别为85.19%、80.77%、92.8%(P>0.05);痊愈率分别为65.6%、59.4%、75%(P>0.05);成本-效果比分别为(细菌清除率)0.41、0.69、0.64;(痊愈率)0.40、0.72、0.63;有效率分别为87.5%、78.125%、93.75%(P<0.05);3种方案治疗下呼吸道感染在痊愈率、细菌清除率上无显著差异,在有效率上有显著差异。结论综合考虑,C方案为较佳方案。     

HIV／TB病人抗结核治疗强化期发生药物性肝炎的研究

目的了解广西地区人类免疫缺陷病毒（HIV）及结核（TB）双重感染病人（HIV／TB病人）,在标化抗结核治疗强化期药物性肝炎的发生情况,分析发生药物性肝炎的影响因素。方法以同期HIV阴性的TB病人作对照,选择16个可能对发生药物性肝炎产生影响的因素进行Spearman相关性分析,对单因素分析有统计学意义的影响因素进行Logistic回归模型多因素分析。结果符合观察条件的HIV／TB病人共369例,药物性肝炎发生率为22．8％（84例）;HIV阴性的TB共350例,药物性肝炎发生率为13．1％（46例）,两组比较差异有统计学意义（Pd0．001）。HIV／TB组治疗失败47例,其中与药物性肝炎相关占63．8％。单因素分析HIV／TB病人药物性肝炎的危险因素为女性、体质量减少、合并乙型肝炎病毒（HBV）或／和丙型肝炎病毒（HCV）感染、既往有肝损伤病史、血清蛋白降低、低CD4^＋T淋巴细胞计数、静脉途径用药、用药后嗜酸性粒细胞计数升高;多因素分析显示：体质量减少、既往有肝损伤病史、低CD4^＋T淋巴细胞计数、静脉用药、用药后嗜酸性粒细胞计数升高,是导致药物性肝炎的危险因素。结论HIV／TB病人抗结核治疗易出现药物性肝炎,对预后影响大;HIV感染后体质下降和免疫异常是导致药物性肝炎发生率高的主要原因。     

Antituberculosis drugs and hepatotoxicity

Isoniazid, pyrazinamide and rifampicin have hepatotoxic potential, and can lead to such reactions during antituberculosis chemotherapy. Most of the hepatotoxic reactions are dose-related; some are, however, caused by drug hypersensitivity. The immunogenetics of antituberculosis drug-induced hepatotoxicity, especially inclusive of acetylaor phenotype polymorphism, have been increasingly unravelled. Other principal clinical risk factors for hepatotoxicity are old age, malnutrition, alcoholism, HIV infection, as well as chronic hepatitis B and C infections. Drug-induced hepatic dysfunction usually occurs within the initial few weeks of the intensive phase of antituberculosis chemotherapy. Vigilant clinical (including patient education on symptoms of hepatitis) and biochemical monitoring are mandatory to improve the outcomes of patients with drug-induced hepatotoxicity during antituberculosis chemotherapy. Some fluoroquinolones like ofloxacin/levofloxacin may have a role in constituting non-hepatotoxic drug regimens for management of tuberculosis (TB) in the presence of hepatic dysfunction. Isoniazid administration is currently the standard therapy for latent TB infection. Rifamycins like rifampicin or rifapentine, alone or in combination with isoniazid, may also be considered as alternatives, pending accumulation of further clinical data. During treatment of latent TB infection, regular follow up is essential to ensure adherence to therapy and facilitate clinical monitoring for hepatic dysfunction. Monitoring of liver chemistry is also required for those patients at risk of drug-induced hepatotoxicity.     

Short communication: antituberculosis drug-induced hepatotoxicity is unexpectedly low in HIV-infected pulmonary tuberculosis patients in Malawi

The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.     

Genetic polymorphisms of NAT2 and CYP2E1 associated with antituberculosis drug-induced hepatotoxicity in Korean patients with pulmonary tuberculosis

Antituberculosis drug-induced hepatitis attributed to isoniazid (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. The aim of this study was to evaluate whether polymorphisms of the NAT2 and/or CYP2E1 genes were associated with antituberculosis drug-induced hepatotoxicity in Korean patients. A total of 132 patients with tuberculosis who received antituberculosis treatment were followed prospectively. Their NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction (PCR) with or without sequencing. Eighteen (13.6%) patients developed antituberculosis drug-induced hepatotoxicity. Regarding NAT2, slow acetylators had a higher incidence of hepatotoxicity than rapid acetylators (36.8% vs. 9.7%, P=0.005) and there was a 3.8-fold risk of hepatotoxicity for the slow acetylators compared to the rapid acetylators. For the CYP2E1 gene, the RsaI polymorphism in the 5' untranslated region, and a polymorphic repetitive sequence at the CYP2E1 5'-flaking region were analyzed; there was no significant association between any CYP2E1 genotype and antituberculosis drug-induced hepatotoxicity. In conclusion, slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatotoxicity; NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity.     

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis

Antituberculosis drug-induced hepatitis is one of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators had significantly higher serum aminotransferase levels than rapid acetylators. Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% CI, 1.58-8.49; P =.003) and age (OR, 1.09; 95% CI, 1.04-1.14; P <.001) were the only 2 independent risk factors for antituberculosis drug-induced hepatitis. In conclusion, slow-acetylator status of NAT2 is a significant susceptibility risk factor for antituberculosis drug-induced hepatitis. Additionally, slow acetylators are prone to develop more severe hepatotoxicity than rapid acetylators. Regular monitoring of serum aminotransferase levels is mandatory in patients receiving antituberculosis treatment, especially in slow acetylators.     

Antituberculosis drug-induced hepatotoxicity: concise up-to-date review

The cornerstone of tuberculosis management is a 6-month course of isoniazid, rifampicin, pyrazinamide and ethambutol. Compliance is crucial for curing tuberculosis. Adverse effects often negatively affect the compliance, because they frequently require a change of treatment, which may have negative consequences for treatment outcome. In this paper we review the incidence, pathology and clinical features of antituberculosis drug-induced hepatotoxicity, discuss the metabolism and mechanisms of toxicity of isoniazid, rifampicin and pyrazinamide, and describe risk factors and management of antituberculosis drug-induced hepatotoxicity. The reported incidence of antituberculosis drug-induced hepatotoxicity, the most serious and potentially fatal adverse reaction, varies between 2% and 28%. Risk factors are advanced age, female sex, slow acetylator status, malnutrition, HIV and pre-existent liver disease. Still, it is difficult to predict what patient will develop hepatotoxicity during tuberculosis treatment. The exact mechanism of antituberculosis drug-induced hepatotoxicity is unknown, but toxic metabolites are suggested to play a crucial role in the development, at least in the case of isoniazid. Priorities for future studies include basic studies to elucidate the mechanism of antituberculosis drug-induced hepatotoxicity, genetic risk factor studies and the development of shorter and safer tuberculosis drug regimens.