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肝活检确诊药物性肝损害的病因及临床特征分析
作者:徐礼通 陈松海 李忠斌 李智 樊和斌 陶颖 陈国凤 纪冬 
单位:430000  武汉  解放军161医院感染科(徐礼通、李智、樊和斌、陶颖) 100039  北京  解放军302医院肝硬化诊疗第二中心(陈松海、李忠斌、陈国凤、纪冬) 
关键词:药物性肝损害 肝活检 病理学 
分类号:R445.1
出版年,卷(期):页码:2018,43(2):130-134
摘要:

[摘要]  目的  探讨药物性肝损害(DILI)的病因及临床特征。方法 回顾性分析2015112月在解放军302医院行肝组织病理学检查确诊的194DILI住院患者的资料,分析其血生化指标、病因及肝组织病理学检查结果,对患者进行随访,分析其复发的预测因素。结果  194例确诊的DILI中,造成肝损害的药物包括中药91(46.9%),解热镇痛药28(14.4%),抗菌素18(9.3%),环境毒物及抗抑郁药均为9(4.6%),保健药及降脂药均为6(3.1%),化疗药5(2.6%),其他原因不详者22(11.3%)。临床分型可见肝细胞损伤型78(40.2%),胆汁淤积型63(32.5%),混合型53(27.3%)。病理结果提示急性损害70(36.1%),慢性损害124(63.9%);慢性损害中炎症程度占比分别为:G019(9.8%)G137(19.1%)G242(21.6%)G319(9.8%)G47(3.6%)。在124例慢性DILI患者中,有27例复发(21.8%),多因素分析显示胆碱酯酶是复发的独立风险预测因素。结论  药物性肝损害发生率逐年升高,中药所致的肝损害所占比例明显上升,胆碱酯酶低是复发的风险因素,临床医生需要掌握其临床特征以做到准确诊断,合理治疗。

[Abstract] Objective To investigate the etiology and clinical features of drug-induced liver injury (DILI). Methods A total of 194 DILI in patients, who underwent liver biopsy in our hospital from January 2015 to December 2015, were enrolled in the study. The etiology, laboratory markers (such as alanine transaminase, aspartate aminotransferase, total bilirubin, gamma- glutamyl transferase and alkaline phosphatase), and the pathological features were analyzed retrospectively. Then, all of the patients were followed up every 3 or 6 months, with a mean of 34.5 months. The risk factors associated with relapse, which was defined as liver enzymes ( such as ALT or TBIL) rising at least 2 times of its upper limit of normal value (ULN), were analyzed with a logistic regression model. Results  In terms of etiology, Traditional Chinese medicine (TCM) was the most common cause of DILI, which accounted for 46.9% of patients, in return followed by acetaminophen-containing drugs (14.4%), antibiotics (9.3%), environmental toxins (4.6%), antidepressant (4.6%), dietary supplement (3.1%), lipid-lowering drugs (3.1%), chemotherapeutic agents (2.6%, and others unknown (11.3%). Of 194 DILI patients, hepatocellular type was observed in 78(40.2%) patients, cholestatic type in 63(32.5%), and mixed type in 53(27.3%). Histological findings showed that 70(36.1%) patients had an acute injury, 124(63.9%) chronic damages, which composed by G0(9.8%), G1(19.1%), G2(21.6%), G3(9.8%), and G4(3.6%) in terms of inflammation level. Twenty-seven cases (21.8%) relapsed after discharge from hospital, multivariate analysis showed that cholinesterase is an independent risk factor which might predict the relapse of DILI patients. Conclusions  The incidence of DILI is increasing, especially induced by TCM, therefore clinicians should master the clinical features of the disease in order to achieve correct diagnosis and establish the optimal treatment strategy.

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