N-乙酰半胱氨酸治疗重症酒精性肝炎的有效性及安全性  

Efficacy and safety of N-acetylcysteine in treatment of severe alcoholic hepatitis

作　　者：宋芳娇 徐天娇 尹艺睿 田华 吕飒 游绍莉 辛绍杰 朱冰 SONG Fangjiao;XU Tianjiao;YIN Yirui;TIAN Hua;LYU Sa;YOU Shaoli;XIN Shaojie;ZHU Bing(Senior Department of Hepatology,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Second Department of Hepatology,Qingdao Sixth People’s Hospital,Qingdao,Shandong 266033,China)

机构地区：[1]中国人民解放军总医院第五医学中心肝病医学部肝病内科,北京100039 [2]青岛市第六人民医院肝病二科,山东青岛266033

出　　处：《临床肝胆病杂志》2024年第12期2484-2491,共8页Journal of Clinical Hepatology

基　　金：国家科技重大专项(2017ZX10203201004);北京市科技计划项目(Z151100003915156)。

摘　　要：目的通过分析N-乙酰半胱氨酸(NAC)治疗重症酒精性肝炎(SAH)的有效性及安全性,为SAH的临床用药提供相关依据。方法对2015年6月—2018年6月中国人民解放军总医院第五医学中心招募的172例马德里判别函数>32分的SAH患者进行前瞻性随机对照研究,分为NAC组(n=84)和对照组(n=86),评价NAC(8 g/d,28 d)治疗对SAH患者的安全性、28 d生化指标的影响,以及28 d、180 d生存率的改善作用。进一步评价NAC对SAH中慢加急性肝衰竭(ACLF-SAH)患者及非ACLF患者(non-ACLF-SAH)28 d及180 d生存率的影响。符合正态分布的计量资料两组间比较采用成组t检验,不满足正态分布的计量资料两组间比较采用Mann-Whitney U检验。Kaplan-Meier法绘制生存曲线,采用Log-rank检验对生存曲线进行比较。单因素和多因素Cox比例风险回归分析独立影响因素。结果NAC治疗期间未发生相关严重不良事件,安全性良好。与对照组相比,NAC对SAH患者28 d生化指标(P值均>0.05)及生存率(P=0.081)无明显改善作用,但可提高SAH患者180 d的生存率(67.4%vs 81.0%,χ^(2)=4.280,P=0.039)。NAC对ACLF-SAH患者28 d及180 d的生存率均无改善作用(P值均>0.05);NAC对non-ACLF-SAH患者28 d生存率无改善作用(P>0.05),但可提高其180 d的生存率(68.4%vs88.9%,χ^(2)=4.883,P=0.027)。多因素Cox回归分析结果显示,是否采用NAC治疗(HR=2.530,95%CI:1.334~4.796,P=0.004)、马德里判别函数(HR=3.852,95%CI:2.032~7.304,P<0.001)、血钠水平(HR=1.948,95%CI:1.079~3.517,P=0.027)是SAH患者180 d生存率的独立影响因素。结论NAC治疗SAH具有较好的安全性,可提高SAH患者180 d的中长期生存率,且中长期生存率受益患者群体主要是non-ACLF-SAH患者。Objective To investigate the efficacy and safety of N-acetylcysteine(NAC)in the treatment of severe alcoholic hepatitis(SAH),and to provide a basis for clinical medication for SAH.Methods A prospective randomized controlled trial was conducted among 172 SAH patients with a Maddrey discriminant function score of>32 points who were recruited by The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to June 2018,and these patients were divided into NAC group with 84 patients and control group with 86 patients.NAC(8 g/day,28 days)was assessed in terms of its safety in SAH patients,its impact on 28-day biochemical parameters,and its role in improving 28-and 180-day survival rates.A further analysis was performed to investigate the effect of NAC on the 28-and 180-day survival rates of SAH patients with acute-on-chronic liver failure(ACLF-SAH patients)and those without acute-on-chronic liver failure(non-ACLF-SAH patients).The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate independent influencing factors.Results No serious adverse events were observed during NAC treatment,suggesting that NAC had a good safety profile.Compared with the control group,NAC did not significantly improve the 28-day biochemical parameters(all P>0.05)and survival rate of SAH patients(P=0.081),but it could improve the 180-day survival rate of SAH patients(67.4%vs 81.0%,χ^(2)=4.280,P=0.039).NAC did not improve the 28-and 180-day survival rates of ACLF-SAH patients(both P>0.05);NAC did not improve the 28-day survival rate of non-ACLF-SAH patients(P>0.05),but it could improve the 180-day survival rate of these patients(68.4%vs 88.9%,χ

关 键 词：肝炎 酒精性 乙酰半胱氨酸 治疗学 

分 类 号：R575.1[医药卫生—消化系统]