水飞蓟制剂预防性治疗抗结核药物性肝损伤效果的Meta分析

目的 评估水飞蓟制剂在预防抗结核药物性肝损伤(ATB-DILI)中的作用。方法 检索MEDLINE、PubMed、Embase和Cochrane对照试验中心注册库(CENTRAL)截至2018年11月30日,水飞蓟制剂与安慰剂相比预防ATB-DILI的随机对照试验研究。所有统计分析均使用STATA12.0软件进行。使用具有95%可信区间(95%CI)的标准化均值差(SMD)和相对危险度(RR)来评估水飞蓟制剂的作用。纳入研究的质量根据Cochrane手册进行评估。使用漏斗图和Egger’s测试评估发生偏倚。采用敏感性分析以评估每项研究对整体效应大小的影响。结果 共纳入5项随机对照试验的1198例患者(585例使用水飞蓟制剂,613例使用安慰剂)。水飞蓟制剂在第4周显著降低了ATB-DILI的发生风险(RR=0.33,95%CI:0.15~0.75, P =0.008)。此外,水飞蓟制剂对接受抗结核药物治疗的患者肝功能有保护作用(ALT: SMD=-0.15,95%CI:-0.24^-0.07, P <0.001;AST:SMD=-0.14,95%CI:-0.23^-0.06, P = 0.001;ALP:SMD=-0.12,95%CI:-0.20^-0.03, P =0.008)。水飞蓟制剂和安慰剂不良反应发生风险相当(RR=1.09,95%CI:0.86~1.39, P =0.47)。结论 水飞蓟制剂的预防性治疗有助于结核病患者开始治疗后4周显著降低ATB-DILI的发生风险。此外,水飞蓟制剂还能显著改善抗结核药物治疗患者的肝功能。

Clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury: A Meta-analysis of randomized controlled trials

Objective To evaluate the clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury (ATB-DILI), since there have always been controversies over the development of Silybum marianum preparation for the prophylactic treatment of ATB-DILI. Methods MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) on Silybum marianum preparation versus placebo in preventing ATB-DILI published up to November 30, 2018. STATA 12.0 software was used for statistical analyses. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI) were used to evaluate the effect of Silybum marianum preparation. The Cochrane handbook was used to assess the quality of RCTs, and funnel plots and Egger’s tests were used to evaluate publication bias. A sensitivity analysis was conducted to assess the influence of each RCT on overall effect. Results A total of five RCTs with 1198 patients were included, and among these patients, 585 received Silybum marianum preparation and 613 received placebo. Silybum marianum preparation significantly reduced the risk of the onset of ATB-DILI at week 4 (RR=0.33, 95%CI: 0.15-0.75, P =0.008). In addition, Silybum marianum preparation had a protective effect on liver function in patients receiving antitubercular agents (alanine aminotransferase: SMD=-0.15, 95% CI:-0.24 to -0.07, P <0.001;aspartate aminotransferase: SMD=-0.14, 95%CI:-0.23 to -0.06, P =0.001;alkaline phosphatase: SMD=-0.12, 95%CI:-0.20 to-0.03, P =0.008). Silybum marianum preparation had a similar risk of adverse events as placebo (RR=1.09, 95%CI: 0.86-1.39, P =0.47). Conclusion In patients with tuberculosis, prophylactic treatment with Silybum marianum preparation can significantly reduce the risk of the onset of ATB-DILI after 4 weeks of treatment. In addition, Silybum marianum preparation can also improve the liver function of patients treated with antitubercular agents.