186例药物性肝损伤患者的临床特征及鉴别

Clinical characteristics and differential diagnosis of 186 patients with drug-induced liver injure

目的探究药物性肝损伤(DILI)的临床特点,轻中度与重度DILI生化特征比较,以及DILI与自身免疫性肝炎(AIH)的鉴别要点。方法将四川大学华西医院2015年1月至2018年3月住院期间诊断的186例DILI患者分为重度DILI组(TBil>5ULN,110例)和轻中度DILI组(76例),鉴别DILI轻中度与重度间特征差异,绘制ROC曲线;对其中行肝穿刺活检术的31例DILI及14例AIH患者进行1年随访,比较DILI和AIH患者首次住院和末次随访的生化指标。结果186例DILI患者以41~60岁为主(93例),女性居多(104例),临床症状不典型;致病药物主要为中草药(97例),及时停用可疑药物并予保肝治疗后,大多预后良好(172例患者好转,14例患者自动出院)。TBil、直接胆红素(DBil)、总胆汁酸(TBA)和甘油三酯(TG)升高,高密度脂蛋白(HDL-C)显著降低及中草药和抗肿瘤药物使用史是鉴别重度与轻中度DILI的主要特征(Z=11.581、11.452、5.629、6.324、-9.926,χ^2=54.107、20.265,P<0.05)。ROC曲线提示TBil 81.80μmol/L,DBil 69.55μmol/L,TBA 70.10μmol/L,TG 1.61mmol/L和HDL-C 0.50mmol/L是区分重度与轻中度DILI的临界值(AUC>0.5)。DILI和AIH患者在入院时除球蛋白(GLB)外(Z=-2.477,P<0.05),生化指标无显著差异(P>0.05),1年随访后,DILI患者肝酶学指标及胆红素指标均显著改善,而AIH患者会出现肝酶学指标的反复异常。结论TBil、DBil、TBA、TG升高和HDL-C降低是区分重度和轻中度DILI的重要参考指标。DILI治疗过程中应动态监测肝功能指标的变化趋势,如指标反复异常,需警惕AIH可能。

Objective To explore the clinical characteristics of drug-induced liver injure(DILI),the biochemical characteristics between mild-moderate DILI and severe DILI,and its differential points from autoimmune hepatitis(AIH).Methods A retrospective analysis was performed on 186 patients with DILI in West China Hospital of Sichuan University from January 2015 to March 2018.It was divided into severe DILI group(TBil>5ULN,110 cases)and mild-moderate DILI group(76 cases),and the characteristic differences between them were identified and analyzed by ROC curve.Thirty-one patients with DILI and 14 patients with AIH who underwent liver biopsy were followed up for 1 year.The biochemical indexes of the first hospitalization and the last follow-up in those patients were compared.Results The majority of DILI patients were aged from 41 to 60 years old(93 cases)and were females(104 cases),with atypical clinical symptoms.The major pathogenic drugs were Chinese herbal medicines(97 cases),and most patients had good prognosis after timely discontinuing suspicious drugs and starting hepatoprotective treatments(172 patients improved,while 14 patients discharged automatically).Increased TBil,DBil,TBA,TG as well as decreased HDL-C and the treatment of Chinese herbal medicines and anti-tumor drugs were the major characteristics to distinguish severe and mild-moderate DILI(Z=11.581,11.452,5.629,6.324,-9.926,χ^2=54.107,20.265,P<0.05).ROC curve indicated that TBil 81.8μmol/L,DBil 69.55μmol/L,TBA 70.1μmol/L,TG 1.61 mmol/L and HDL-C 0.50mmol/L were the cut-off values to distinguish severe and mild-moderate DILI(AUC>0.5).With the exception of GLB(Z=-2.477,P<0.05),there was no significant difference in biochemical indexes in DILI and AIH patients at the first admission(P>0.05).After 1-year follow-up,levels of liver function and bilirubin in DILI patients were significantly improved,while repeated abnormalities of liver enzyme indexes were observed in AIH patients.Conclusions Increased TBil,DBil,TBA,TG as well as decreased HDL-C are important reference indexes to distinguish severe DILI from mild-moderate DILI.In the course of DILI treatment,we should monitor the change trend of liver function index dynamically.It should be alert to the possibility of AIH if the index is abnormal repeatedly.