138例药物性肝损伤患者的临床特征及肝脏组织学改变  

Clinical and pathological features in 138 cases of drug-induced liver injury

作　　者：赖荣陶[1] 王晖[1] 桂红莲[1] 叶敏贞[1] 戴维佳[1] 项晓刚[1] 赵钢德[1] 王伟静[1] 谢青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《中华肝脏病杂志》2012年第3期185-189,共5页Chinese Journal of Hepatology

摘　　要：目的探讨当前引起药物性肝损伤的主要药物种类，了解患者的临床特征及肝脏组织学改变情况，以期为临床诊断提供思路。方法收集2008年4月至2010年4月连续收治临床诊断为药物性肝损伤（DILI）的138例患者资料，入选标准为依据Roussel Uclaf因果关系评估法评分值≥6分。依I临床分型分为3组：肝细胞损伤型组、胆汁淤积型组和混合型组。3型诊断标准为：（1）肝细胞损伤型：[ALT／正常值上限（ULN）]／（碱性磷酸酶／ULN）≥5；（2）胆汁淤积型：（ALT／ULN）／（碱性磷酸酶／uLN）≤2；（3）混合型：2〈（ALT／ULN）／（碱性磷酸酶／ULN）〈5。分别统计其一般资料、临床表现、生物化学及免疫学指标，并对其中66例行肝活组织检查患者的肝脏组织学改变进行分析。多组均数比较采用单因素方差分析，多组非参数统计采用Kruskal-Wallis检验，两组比较的非参数统计采用Wilcoxon秩和检验，临床与病理学分型的一致性比较采用kappa检验，两样本率的比较采用，检验和Fisher’s精确概率法。结果本研究中致肝损伤药物主要有中草药（包括中成药，占53．8％）、抗微生物药（8．0％）以及保健品（6．蛳）。依据血清生物化学指标进行临床分型，其与病理损伤分型的一致性（kappa=0．63，P〈0．05）优于发病时临床分型与病理损伤分型的一致陛（kappa=0．25，P〈0．05）。DILI患者的病理学特征主要有大泡陛脂肪变性、小泡性脂肪变性、胆汁淤积、肝细胞凋亡、上皮样肉芽肿、嗜酸性粒细胞及嗜中性粒细胞浸润，淋巴细胞、浆细胞浸润及铁沉着。胆汁淤积型及混合型患者肝组织学改良HA]炎症坏死评分和Ishak纤维化评分均高于肝细胞损伤组护值均〈0．05）。结论中草药（包括中成药）是导致肝损伤的重要原因；同一时相临床分型与病理损伤分型有较好的一致性；胆�Objective To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury （DILI）, in order to gain insights into potential diagnostic factors for DILI. Methods A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method （RUCAM） had been used to diagnose DILL Only cases that had scored as highly probable or probable （≥ 6 points by RUCAM） were included in this study. The patients＇ general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to clasify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types. Results Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy （≥3 days after laboratory results） （kappa = 0.63, P 〈 0.05） than at the onset of DILI （kappa = 0.25, P 〈 0.05）. All modified hepatic activity index （HAI） necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type （P 〈 0.01 and P 〈 0.05, respectively）. Conclusion Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILL The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic

关 键 词：药物性肝损伤 病理学 组织学 

分 类 号：R595.3[医药卫生—内科学] R575[医药卫生—临床医学]