N-乙酰半胱氨酸联合双环醇治疗抗结核药物所致的药物性肝损伤患者疗效研究*

目的 观察应用N-乙酰半胱氨酸(NAC)联合双环醇治疗抗结核药物所致的药物性肝损伤(DILI)患者的疗效。方法 2018年1月～2020年1月我院诊治的因肺结核接受抗结核药物治疗导致的DILI患者76例,随机分为A组38例和B组38例,分别给予双环醇或双环醇联合NAC治疗,两组均连续治疗1个月或至肝功能正常。因本组患者被发现得早,肝功能损害较轻,未停止抗结核治疗。采用黄嘌呤氧化法和硫代巴比妥酸法检测血清超氧化物歧化酶(SOD)和丙二醛(MDA)水平,采用双抗体夹心ELISA法检测血清白细胞介素-6(IL-6)水平,采用免疫散射速率比浊法检测血清C-反应蛋白(CRP)水平。结果 在治疗结束时,B组血清AST、ALT和GGT水平分别为(39.3±10.5)U/L、(35.9±32.5)U/L和(58.4±10.5)U/L,显著低于A组【分别为(75.4±14.6)U/L、(86.9±44.8)U/L和(95.8±14.5)U/L,P<0.05】;B组血清SOD水平为(83.5±8.0)U/L,显著高于A组【(74.5±7.3)U/L,P<0.05】,而血清MDA、IL-6和CRP水平分别为(5.0±0.8)μmol/L、(4.1±1.2)ng/L和(9.1±2.2)mg/L,显著低于A组【分别为(6.9±1.2)μmol/L、(6.8±2.4)ng/L和(14.5±3.7)mg/L,P<0.05】;在治疗过程中,B组与A组出现头晕、腹泻、皮疹、发热和恶性呕吐发生率无显著性差异(18.4%对15.8%,P>0.05)。结论 应用NAC联合双环醇治疗抗结核药物所致的DILI患者可获得较好的治疗效果,能促进血清肝功能指标的恢复,可能与抑制了机体氧化应激和炎症反应有关,同时患者加用药物后也未明显增加用不良反应发生率,但其长期治疗效果还需要进一步观察。

Efficacy of N-acetylcysteine and dicyclol combination in the treatment of patients with antituberculous drugs-induced liver injury

Objective This study aimed to investigate the efficacy of N-acetylcysteine (NAC) and dicyclol combination in the treatment of patients with antituberculous drugs-induced liver injury (DILI). Methods Seventy-six patients with DILI caused by anti-tuberculocidal agents for pulmonary tuberculosis were enrolled in our hospital between January 2018 and January 2020, and were randomly divided into group A and group B, with 38 cases in each group. All patients received symptomatic supporting treatment and nutritional supplement without discontinuing antituberculosis medication. The patients in group A were treated with bicyclol, and those in group B received bicyclol and NAC combination therapy for one month or didn't stop until serum liver function tests recovered. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), gamma glutamine transferase (GGT), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and C-reactive protein (CRP) levels were detected. Results At the end of treatment, serum AST, ALT and GGT levels in group B were (39.3±10.5)U/L, (35.9±32.5)U/L and (58.4±10.5)U/L, significantly lower than (75.4±14.6)U/L, (86.9±44.8)U/L and (95.8±14.5)U/L, respectively, P<0.05] in group A; serum SOD level was (83.5±8.0)U/L, significantly higher than (74.5±7.3)U/L, P<0.05], while serum MDA, IL-6 and CRP levels were (5.0±0.8)μmol/L, (4.1±1.2)ng/L and (9.1±2.2)mg/L, all significantly lower than (6.9±1.2)μmol/L, (6.8±2.4)ng/L and (14.5±3.7)mg/L, respectively, P<0.05] in group A; the complications such as dizziness, diarrhea, rash, fever, and nausea and vomiting in the two groups were not significantly different (18.4% vs. 15.8%, P>0.05). Conclusion The administration of bicyclol and NAC combination in treatment of patients with DILI caused by anti-tuberculosis agents could achieve a good curing efficacy with improved recovery of liver function index, which might be related to the inhibition of oxidative stress and inflammatory reactions. The long-term efficacy still needs further observation.