Gu Jin, Tang Shen-Jie, Tan Shou-Yong, Wu Qi, Zhang Xia, Liu Cun-Xu, Gao Xu-Sheng, Yuan Bao-Dong, Han Li-Jun, Gao Ai-Ping, Wu Mei-Ying, Huang Li-Hua, Ma Jun, Xiao He-Ping
Clinic and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine China.
Beijing Chest Hospital, Capital Medical University China.
Int J Clin Exp Med. 2015 Mar 15;8(3):4320-7. eCollection 2015.
To assess the clinical efficacy and safety of Silibinin in preventing drug-induced liver injury (DILI) in the general population (high-risk patients with non-drug induced liver injury).
A prospective, multi-center, randomized, open-label and controlled trial was conducted with 568 patients undergoing primary treatment of pulmonary tuberculosis. The study included 277 patients in experimental group and 291 patients in control group. The patients in the two group were treated with conventional 2HREZ (S)/4HR for tuberculosis (TB), and additional Silibinin capsules (oral administration of 70 mg/time, 3 times/day for 8 weeks in experimental group. Outcomes of liver function, interruption of anti-TB treatment and therapeutic results, as well as adverse reactions were observed and analyzed.
At 2, 4 and 8 weeks of treatment, the incidences of liver injury in experimental group were 3.97%, 1.44% and 2.17%, respectively; the incidences in control group were 4.12%, 4.12% and 2.41%, respectively. Statistical analysis showed that there was no difference in the incidence between the two groups at each treatment period (P>0.05). At 8 weeks, the numbers of patients diagnosed of DILI were 18 (7.22%) and 27 (9.28%) in experimental and control groups, respectively (P>0.05). 34.30% and 27.49% of the patients in experimental and control groups had transient abnormal liver function or symptoms, respectively; similar percentages (3.25% and 6.19%) of the patients in two groups have liver function injury and symptoms, and were suspended for anti-TB treatment (P>0.05). The incidence of anorexia and nausea symptoms was lower in experimental group than in control group, and the differences were significant at 4 and 8 weeks (P<0.05). 8 weeks after the treatment, 98.30% of the sputum smear culture were negative in experimental group, which was significantly higher (P<0.01) than that in control group (92.98%).
Preventive hepatoprotective therapy in the general population may reduce drug discontinuation rate, improve patient's compliance and outcomes of anti-TB treatment.
评估水飞蓟宾在普通人群（非药物性肝损伤的高危患者）中预防药物性肝损伤（DILI）的临床疗效和安全性。
对568例接受肺结核初始治疗的患者进行了一项前瞻性、多中心、随机、开放标签和对照试验。研究包括277例试验组患者和291例对照组患者。两组患者均采用常规的2HREZ（S）/4HR方案治疗肺结核，试验组额外给予水飞蓟宾胶囊（口服，每次70mg，每日3次，共8周）。观察并分析肝功能结果、抗结核治疗中断情况和治疗效果以及不良反应。
治疗2、4和8周时，试验组肝损伤发生率分别为3.97%、1.44%和2.17%；对照组分别为4.12%、4.12%和2.41%。统计分析表明，各治疗阶段两组发生率无差异（P>0.05）。8周时，试验组和对照组诊断为DILI的患者数分别为18例（7.22%）和27例（9.28%）（P>0.05）。试验组和对照组分别有34.30%和27.49%的患者出现短暂肝功能异常或症状；两组肝功能损伤并出现症状且中断抗结核治疗的患者比例相似（3.25%和6.19%）（P>0.05）。试验组厌食和恶心症状的发生率低于对照组，在4周和8周时差异有统计学意义（P<0.05）。治疗8周后，试验组痰涂片培养阴性率为98.30%，显著高于对照组（92.98%）（P<0.01）。
普通人群中的预防性保肝治疗可能降低停药率，提高患者对抗结核治疗的依从性和治疗效果。
