抗结核治疗过程中出现药物性肝损伤对结核病疗效的影响

Effects of drug-induced liver injury on the efficacy of antitubeiculosis therapy

目的探讨药物性肝损伤对初治涂阳肺结核患者抗结核治疗疗效的影响。方法采用病例对照回顾性分析,选取2017年1月-2017年12月于广州市胸科医院住院确诊为初治涂阳肺结核并于抗结核过程中出现药物性肝损伤的患者207例作为肝损组,采用随机数字表法随机选取同期没出现药物性肝损伤患者207例作为对照组。两组患者初始治疗方案均为2HRZE/4HR,根据体质量调整用药,并确保肝损组后期未对治疗方案进行过大的调整。比较两组患者治疗2月末、6月末痰菌阴转率、影像学病灶吸收情况、空洞闭合情况及治疗转归等方面的差异。结果肝损组和对照组2月末痰菌阴转率为37.68%(78/207)和76.81%(159/207),差异有统计学意义(χ^2值64.75,P<0.01);3月末痰菌阴转率为70.01%(147/207);和91.30%(189/207),差异有统计学意义(χ^2值27.87,P<0.01)。肝损组2月末病灶恶化占比20.29%(42/207),吸收占比52.17%(108/207);对照组2月末病灶恶化占比4.35%(9/207),吸收占比83.61%(171/207),差异有统计学意义(χ^2=47.12,P<0.01)。肝损组与对照组治疗2月末时空洞缩小、不变、恶化的比率分别为46.67%(63/135)、31.11%(42/135)、22.22%(30/135)与84.09%(111/132)、13.64%(18/132)、2.27%(3/132),差异有统计学意义(U=6.66,P<0.01)。肝损组与对照组治疗成功率分别为92.75%(192/207)、97.10%(201/207),差异有统计学意义(χ^2=4.06,P=0.04)。结论抗结核治疗过程中出现肝损可能会使痰菌阴转延迟,肺部病灶及空洞吸收延迟、恶化增多,影响治疗成功率、耐药率提升、最终导致治疗失败,临床应对此有足够的重视。

Objective To investigate the effect of drug-induced liver injury on anti-tuberculosis treatment in patients with initial smear positive pulmonary tuberculosis. Methods Case-control was retrospectively analyzed. The selection between January 2017 and December 2017 in Guangzhou chest hospital diagnosed with initial smear-positive pulmonary tuberculosis and tuberculosis,were drug-induced liver injury as liver damage group, 207 cases who were randomly selected by random number table method didn t appear in drug-induced liver injury as control group in the same period. The initial treatment regimens of patients in both groups were 2HRZE/4HR. The medication was adjusted according to the body mass, and the treatment regimens were not adjusted too much in the later stage of liver damage group. The sputum negative conversion rate, imaging lesion absorption, cavity closure and treatment outcome were compared between the two groups at the end of 2 months and 6 months of treatment cycle. Results At the end of 2 months, the sputum negative conversion rate of the liver damage group and the control group was 37.68%(78/207) and 76.81%(159/207), the difference was statistically significant (χ^2=64.75, P <0.01). At the end of 3 months the sputum negative conversion rate was 70.01%(147/207) and 91.30%(189/207), the difference was statistically significant (χ^2= 27.87, P <0.01). In the liver damage group, the lesion deterioration rate was 20.29%(42/207) at the end of 2 months, and the absorption rate was 52.17%(108/207). In the control group, the rate of lesion deterioration at the end of 2 months was 4.35%(9/207), and the rate of absorption was 83.61%(171/207), the difference was statistically significant (χ^2= 47.12, P <0.01). At the end of 2 months, the rates of shrinkage, invariability and deterioration in the liver lesion group and the control group were 46.67%(63/135), 31.11%(42/135), 22.22%(30/135), 84.09%(111/132), 13.64%(18/132) and 2.27%(3/132), respectively, with statistically significant difference (U value=6.66, P <0.01). The treatment success rate of the liver damage group and the control group was 92.75%(192/207) and 97.10%(201/207), respectively, with statistically significant difference (χ^2=4.06, P =0.04). Conclusion Liver damage during anti-tuberculosis treatment may delay the negative transformation of sputum bacteria, delay and aggravate the absorption of lung lesions and cavities, affect the success rate of treatment, increase the rate of drug resistance, and ultimately lead to treatment failure.