肝脏 ›› 2017, Vol. 22 ›› Issue (12): 1090-1093.

• 论 著 • 上一篇    下一篇

熊去氧胆酸联合S-腺苷蛋氨酸治疗胆汁淤积型药物性肝损伤的疗效分

叶艳菊,俞建平,徐玉敏,王晖,谢青   

  1. 311300 浙江省杭州市临安区人民医院感染科(叶艳菊,俞建平);上海交通大学医学院附属瑞金医院感染科(徐玉敏,王晖,谢青)
  • 收稿日期:2017-08-03 出版日期:2020-06-15 发布日期:2020-06-15
  • 通讯作者: 徐玉敏,Email:xym121@163.com
  • 基金资助:
    国家十三五科技重大专项(2017ZX10202202-005-004,2017ZX10203201-008);上海市公共卫生三年行动计划重点学科建设项目传染病与卫生微生物学(15GWZK0102);上海市卫生局面上项目(201540038)

The treatment effect of ursodeoxycholic acid combined with S-adenosyl-L-methionine on drug-induced cholestatic liver injury

YE Yan-ju, YU Jian-ping, XU Yu-min, WANG Hui, XIE Qing.   

  • Received:2017-08-03 Online:2020-06-15 Published:2020-06-15
  • Contact: XU Yu-min, Email:xym121@163.com

摘要: 目的 观察熊去氧胆酸(UDCA)联合S-腺苷蛋氨酸(SAMe)在治疗胆汁淤积型药物性肝损伤中的疗效。方法 回顾性分析瑞金医院感染科2013年1月至2017年5月胆汁淤积型药物性肝损伤84例住院患者,在接受甘草酸制剂等的护肝治疗基础上46例患者采用UDCA 15 mg/(kg·d)口服及SAMe (1.0 g/d)静滴治疗4周,38例患者单用SAMe治疗,进行疗效对比,并随访24周。结果 4周后UDCA+SAMe组有效率97.83%,单用SAMe组84.21%,差异有统计学意义(P<0.05)。UDCA+SAMe组TBil(54.0±13.8) μmol/L、DBil(25.4±10.2) μmol/L、ALP(78.7±29.3) μmol/L、GGT(81.8±28.5) μmol/L,明显优于单用SAMe组TBil(P=0.00)、DBil(P=0.00)、ALP(P=0.00)、GGT(P=0.00),差异有统计学意义(P<0.05)。治疗结束后24周内随访,单用SAMe组有2例因肝功能再次异常入院,其中1例抗核抗体、抗双链DNA抗体、抗平滑肌抗体出现阳性,肝活检提示药物相关性自身免疫性肝炎,UDCA+SAMe组无一例出现此情况,两组差异无统计学意义。治疗中和治疗结束后均未见药物相关不良反应。结论 UDCA联合SAMe治疗胆汁淤积型药物性肝损伤的疗效优于单用SAMe,且安全性好,值得临床推广,UDCA可能对药物相关性自身免疫性肝炎具有一定预防作用,有待进一步研究证实。

关键词: 熊去氧胆酸, S-腺苷蛋氨酸, 药物性肝损伤, 胆汁淤积, 药物相关性自身免疫性肝炎

Abstract: Objective To investigate the efficacy of ursodeoxycholic acid combined with S-adenosyl-L-methionine therapy in drug-induced cholestatic liver injury.Methods A retrospective analysis of 84 patients with drug-induced cholestatic liver injury from January 2013 to May 2015 in our hospital was conducted. Patients were divided into two groups depending on therapeutic regimen, including 46 patients receiving ursodesoxycholic acid and S-adenosyl-L-methionine combination therapy for 4 weeks in treatment group, and 38 patients receiving S-adenosyl-L-methionine in control group. All patients were followed up for 24 weeks, and the clinical outcomes were accessed.Results After 4-week treatment, patients in treatment group had higher response rate than those in control group (97.83% vs 84.21%, P=0.02). Furthermore, the liver function indexes, including total bilirubin, direct bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase, were all significantly improved in treatment group compared with those in control group (all P<0.05). During 24-week follow-up, two patients in control group were re-hospitalized due to abnormal liver function, including one patient with positive autoantibody and histopathologically diagnosed of drug induced liver injury-associated-autoimmune hepatitis. However, no similar case was observed in treatment group. No adverse effect was observed in both groups during and after treatment.Conclusion Ursodeoxycholic acid and S-adenosyl-L-methionine combination therapy might be more effective than S-adenosyl-L-methionine monotherapy for drug-induced cholestatic liver injury. Ursodeoxycholic acid might putatively contribute to prevention of autoimmune hepatitis, which needs to be further investigated.

Key words: Ursodeoxycholic acid, S-adenosyl-L-methionine, Drug-induced liver injury, Cholestasis, Drug- induced liver injury-associated-autoimmune hepatitis