白鲜皮制剂相关肝损伤的药物流行病学特征分析

Analysis of epidemiological characteristics of drug induced liver injury associated with Baixianpi Preparations

该文通过对中草药肝损伤研究云平台数据库(hilicloud.net)中三级甲等肝病专科医院2008—2016年白鲜皮制剂相关药物性肝损伤(drug-induced liver injury,DILI)的住院病例及2012—2016年不良反应自发上报的白鲜皮制剂相关DILI病例(ADR病例)进行回顾性分析。三级甲等肝病专科医院白鲜皮制剂相关DILI住院病例25例,其中达到《中草药相关肝损伤临床诊疗指南》临床诊断标准的有14例。不良反应自发上报白鲜皮制剂相关DILI报告74例,合理用药分析发现其中18. 92%病例存在不合理用药情况,包括多药联用(21. 43%)、超剂量使用(28. 57%)、重复用药(50%); 47例ADR病例中单用白鲜皮制剂的DILI用药原因主要为银屑病、白癜风(合计占59. 57%);所涉及白鲜皮制剂服药到发生肝损伤的时间跨度为1～366 d,中位数18 d,折算后白鲜皮剂量范围为0. 09～12 g·d-1,服药到发生肝损伤的白鲜皮累积剂量范围为1. 1～336 g,用药时间和剂量分布跨度大,未发现明显用药时间、用药剂量与发生肝损伤的相关性。研究提示白鲜皮制剂相关DILI多发生在银屑病、白癜风等免疫性相关疾病患者,存在显著个体差异,且用药时间、用药剂量与发生肝损伤无明显相关性,具有免疫特异质肝损伤的属性。临床用药应高度重视白鲜皮制剂引起肝损伤的风险,加强对其特异质肝损伤机制以及不合理用药等风险因素的研究,开展风险获益比评估,提高白鲜皮制剂安全用药风险防控水平。

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d^-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.