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析

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

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UDCA15 mg/(kg·d)口服及SAMe(1.0g/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。

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 gammaglutamyl transpeptidase,were all significantly improved in treatment group compared with those in control group（all P0.05）.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-associatedautoimmune 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.