急性重症药物性肝损伤43例临床分析

由于药物或其代谢产物引起的肝细胞毒性损害或肝脏对药物及代谢产物的过敏反应所致的疾病称为药物性肝损害(药物性肝损伤)或药物性肝病(drug induced liver injury,DILI)。近年来,药物性肝病的发生率呈不断上升趋势,据世界卫生组织(WHO)统计,药物性肝损伤已经上升为全球死亡原因的第五位。目前,国内外研究一致认为几乎各个种类的药物都可以引起药物性肝病的发生。随着人口老龄化社会的到来,多种基础疾病并发,加之一些新药不断问世,使发生DILI的危险日益增加。医疗水平发展不平衡,过度医疗用药、滥用药物及保健品等导致的药物性肝损伤越来越受到医疗工作者的重视。大部分药物性肝损伤预后较好,也有部分会发展成为重症病例,给患者带来较大的危害和经济负担。现就我科近10年来收治的43例急性重症药物性肝损伤患者的病因和临床特点做一分析。     

药物性肝损伤的流行病学

<正>一、药物性肝损伤概念和分类药物性肝损伤(DILI)是指人体暴露于常规剂量或高剂量药物后,因药物本身或其代谢产物对肝脏的直接毒性,或人体对药物或其代谢产物产生过敏或代谢特异质反应而导致的肝脏损伤[1]。DILI通常分为两类,特异质型肝损伤和固有型肝损伤[1]。前者主要为人体对药物或其代谢产物产生过敏或代谢特异质反应,具有不可预测性,潜伏期较长或不确定,剂量依赖性较     

药物性肝病的诊断与治疗进展

药物性肝病(DILD)是指在使用某种或几种药物后,由药物或其代谢产物引起的肝脏损害。随着新药不断研发和应用于临床,药物性肝病的发病率也在逐年增高,引起人们对药物性肝损伤的重视及研究。此文主要就药物性肝病的诊断与治疗进展作一综述。     

特殊人群的药物性肝损伤

<正>由于药物的不规范使用和人体对药物的特异性反应,目前药物性肝损伤(DILI)的发生率呈上升趋势,已经上升为全球肝病死亡原因的第5位~[1],不仅影响原发疾病的治疗,而且造成肝脏不同程度的损伤,应引起药物研究者、生产者、使用者、受用者、国家相关部门的高度重视。药物性肝损伤(DILI)是指人体暴露于常规剂量或高剂量药物后,因药物本身或其代谢产物对肝脏的直接毒性,或人体对药物或其代谢产物产生过敏或代谢     

自身免疫样药物性肝损伤研究进展

正药物性肝损伤(DILI)是指由各类处方或非处方化学药物、生物制剂、传统中药、天然药品、保健品、膳食补充剂及其代谢产物乃至辅料所诱发的肝损伤。大量的研究发现有超过1 000种的药物(包括中草药及膳食补充剂)可引起药物性肝损伤~([1])。DILI可表现为急性或慢性肝脏病变,大多数患者在停药后可     

不同类型急性药物性肝炎的诊疗分析

药物性肝损伤是指由母体药物或其代谢产物引起的肝脏损害.2006年1月起,我们对接受抗肿瘤和抗结核药物治疗的患者肝功能和肝外临床表现进行了动态监测.现报告如下.     

药物性肝病的治疗

药物性肝损伤是临床药物运用和安全性中的重要问题 ,也是新药上市后撤药的最常见原因。临床常见的有抗痨药物 (异烟肼 )、抗菌素和化疗药物使用引起的肝损伤、扑热息痛肝毒性、儿童中使用水杨酸盐引起的小囊泡性脂肪肝和Reye’s综合征等。药物性肝损伤只有少部分是由已知有肝损伤的药物引起 ,这类药物具有可预见的剂量依赖的毒性 ,如扑热息痛 ,而绝大多数药物引起的肝损伤是特应性反应 (idiosyncraticreactions) ,机制不明确 ,难以预测 ,有特异的个体易感性因素参与 ,诊断和治疗难度较高。药物性肝损伤的机制包括药物本身及其代谢产物的毒…     

药物性肝病诊治的困惑和建议

药物性肝病（drug—induced liver diseases）是指在使用某种或几种药物后，由药物本身或其代谢产物引起的肝脏损害。在已上市应用的化学性或生物性药物中，有1100种以上具有潜在的肝毒性，很多药物的赋形剂、中草药以及保健药亦有导致肝损伤的可能。欲更有效地监测和预防日益增多的药物性肝损伤，需要在认识药物性肝病现行诊治原则的基础上。分析其中存在的主要问题。探讨有效可行的诊治策略。     

老年人药物性肝损伤的特点与防治

药物性肝损伤（drug-induced liver injury,DILI）,是指由于药物本身或其代谢产物毒性作用以及特殊体质对药物的超敏感性或耐受性降低引起的肝脏损伤.老年人由于器官功能衰退、肝脏对药物毒性的耐受性降低,同时常常因其合并多种疾病、服用的药物种类和数量多等原因,发生药物性肝损害的风险显著增高.     

药物性肝损伤的发病机理

根据发病机理 ,药物性肝损伤分为中毒性和宿主药物特异体质性两类。中毒性肝损伤缘于药物本身或其代谢产物的肝毒性所致 ;药物特异体质性肝损伤进一步分为过敏反应与遗传性药物代谢异常两种 ,前者为一种针对肝脏的免疫反应 ,由代谢产物和肝细胞蛋白结合后引发 ;后者则仍是一种中毒性肝损伤 ,乃由于药物代谢异常使得肝毒性代谢产物生成增多所致。一、中毒性肝损伤的机理大部分药物在肝脏经细胞色素Ｐ45 0 (ＣＹＰ)氧化或还原代谢后 ,与葡萄糖醛酸、硫酸等结合或经乙酰化而变为水溶性 ,尔后由尿液或胆汁排泄。药物经ＣＹＰ代谢产生的亲电子基…     

化疗药物所致肝损伤128例临床分析

目的分析化疗药物所致药物性肝损伤(drug induced liver injury,DILI)的临床特点,为有效降低DILI发病率,减少病死率提供临床依据。方法根据2015年版《药物性肝损伤诊治指南》,收集我院2012年1月—2016年12月128例化疗药物所致DILI住院患者临床资料,分析化疗药物种类,出现DILI的时间、严重程度、治疗方式及临床效果。结果本组患者共128例,男性46例(30.51%),女性82例(69.49%),其中最小年龄24.0岁,最大82.0岁,平均(53.2±5.4)岁。使用化疗药物到发生肝损伤时间从2.0~30.0 d,平均(16.3±2.4)d。引起DILI的化疗药物主要有紫杉醇、铂类、环磷酰胺、阿霉素等,联合使用化疗药物可增加肝损伤的发生率及程度。本组患者中DILI的程度:1级(轻度肝损伤)74例(57.81%),2级(中度肝损伤)44例(34.38%),3级(重度肝损伤)8例(6.25%),4级(肝衰竭)1例(0.78%),5级(死亡)1例(0.78%)。治疗方式根据2007年版《急性药物肝损伤诊治建议》(草案):1级肝损伤患者继续使用化疗药物,同时应用口服多烯磷脂酰胆碱胶囊及甘草酸二铵肠溶胶囊;2级肝损伤给予多烯磷脂酰胆碱注射液、异甘草酸镁注射液静脉滴注;3级肝损伤给予多烯磷脂酰胆碱注射液、异甘草酸镁注射液、丁二磺腺苷蛋酸注射液静脉滴注,必要时使用激素及血浆置换。4级、5级除患者给予上述常规治疗外,适时给予激素及血浆置换。多数患者预后良好,治愈117例(91.40%),死亡1例(0.78%),慢性化发展为肝硬化2例(1.50%),放弃治疗8例(6.25%)。结论化疗药物所致DILI并不少见,接受化疗的患者常规监测肝功能,及时发现DILI并积极有效处理,绝大多数化疗所致DILI可治愈且预后良好。     

药物性肝损害的危险因素、诊断规范及停药标准

药物性肝损害是指药物本身或其代谢产物引起的肝损害,是引起肝衰竭的重要原因之一。目前还缺乏有效的预测指标及诊疗手段。从易感因素、诊断和评价标准等方面对药物性肝损害进行介绍。了解药物性肝损害的最新进展,有利于及时发现药物性肝损害的易感患者;合理运用各种评价标准,有助于药物性肝损害的规范化诊疗。     

药物性肝损伤合并肝外药物不良反应的发生机制及诊疗现状

药物性肝损伤(DILI)合并肝外药物不良反应(EHADR)是指由导致肝损伤的同一药物所致的、与DILI同时或先后发生的肝外组织器官的损伤,例如皮肤、胃肠道、血液系统、心血管系统、骨关节系统等的损伤,是在关注DILI的同时也应加以重视的重要临床问题。DILI合并EHADR并不少见,其发病机制可能与药物的理化性质、分布、代谢、排泄、生物学活性、免疫学特性,以及宿主遗传背景及基础疾病等多方面的因素相关,其诊疗较单纯DILI更具有挑战性。     

Serum biomarkers of drug‐induced liver injury: Current status and future directions

Drug‐induced liver injury (DILI), which is caused by drugs and herbal or dietary supplements, remains a serious concern for drug developers, regulators, and clinicians; however, serum biomarkers utilized to detect and monitor DILI have not changed in decades and have limitations. Data‐driven mathematical modeling that incorporates the release and clearance kinetics of traditional biomarkers has improved their use in the prediction of liver safety liabilities for new drug candidates. Several newer biomarkers have shown promise in terms of liver specificity, predicting the outcome of DILI events, and providing insight into its underlying mechanisms. For these new biomarkers to be qualified for regulatory acceptance, it will require their assessment in large numbers of patients who are receiving a wide range of compounds and who develop a broad spectrum of liver injuries. The ongoing and evolving international biomarker consortia should play a major role in this effort, which is likely to transform the assessment of liver safety in clinical trials and in the clinic.     

Predicting idiosyncratic drug-induced liver injury – some recent advances

Drug-induced liver injury (DILI) is a major challenge for the pharmaceutical industry, regulatory authorities, and clinicians. It is usually categorized into ‘intrinsic’ and ‘idiosyncratic’, but DILI caused by most drugs is of an idiosyncratic nature and usually cannot be predicted from the regulatory required animal toxicity studies. Unfortunately, some individuals exposed to therapeutic dose will develop idiosyncratic DILI that might involve severe clinical outcome, and no biomarker is available to identify the susceptible patients prior to drug treatment. In this editorial, we summarized the recent advances in predicting idiosyncratic DILI and provided the perspectives to improve the prediction.     

The diagnosis and management of idiosyncratic drug‐induced liver injury

Drug‐induced liver injury (DILI) is an uncommon but important cause of liver disease that can arise after exposure to a multitude of drugs and herbal and dietary supplements. The severity of idiosyncratic DILI varies from mild serum aminotransferase elevations to the development of severe liver injury that can progress to acute liver failure resulting in death or liver transplantation within days of DILI onset. Chronic liver injury that persists for more than 6 months after DILI onset is also becoming increasingly recognized in up to 20% of DILI patients. Host demographic (age, gender, race), clinical and laboratory features at DILI onset have been associated with the severity and outcome of liver injury in DILI patients. In addition to cessation of the suspect drug, other medical interventions including the use of N‐acetylcysteine and corticosteroids in selected patients have shown some clinical benefit, but additional prospective studies are needed. A number of promising diagnostic, prognostic and mechanistic serum and genetic biomarkers may help improve our understanding of the pathogenesis and treatment of idiosyncratic DILI.     

医药结合,助力药物性肝损伤精准防控

当今药物性肝损伤(DILI)不仅是国际肝病领域关注的热点,也是全球安全用药关注的热点问题。由于缺少特异性检测指标,DILI误诊率高,也容易造成用药安全的误导,中草药所致DILI成因更复杂,临床诊断更棘手,防控难度更大。为此,呼吁临床专家与药学专家携手合作,医药结合,临床科研结合,构建DILI客观辨识策略和方法,科学厘清DILI与药物之间的因果关系,实现DILI精准诊断;科学阐明DILI成因和机制,从易感人群、易感物质和合理使用等方面实现DILI精准防控。同时建议,要进一步重视和加强中草药肝损伤研究,保证中药临床用药安全,促进中医药事业健康发展。     

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM:To identify the proportion,causes and the nature of drug-induced liver injury(DILI) in patients with notably elevated alanine aminotransferase(ALT).METHODS:All the inpatients with ALT levels above 10 times upper limit of normal range(ULN) were retrospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period.Relevant clinical information was obtained from medical records.Alternative causes of ALT elevations were examined for each patient,including biliary abnormality,viral hepatitis,hemodynamic injury,malignancy,DILI or undetermined and other causes.All suspected DILI cases were causality assessed using the Council for International Organizations of Medical Sciences scale,and only the cases classified as highly probable,probable,or possible were diagnosed as DILI.Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors.RESULTS:A total of 129 cases with ALT 10 ULN were identified.Hemodynamic injury(n = 46,35.7%),DILI(n = 25,19.4%) and malignancy(n = 21,16.3%) were the top three causes of liver injury.Peak ALT values were lower in DILI patients than in patients with hemodynamic injury(14.5 ± 5.6 ULN vs 32.5 ± 30.7 ULN,P = 0.001).Among DILI patients,one(4%) case was classified as definite,19(76%) cases were classified as probable and 5(20%) as possible according to the CIOMS scale.A hepatocellular pattern was observed in 23(92%) cases and mixed in 2(8%).The extent of severity of liver injury was mild in 21(84%) patients and moderate in 4(16%).Before discharge,10(40%) patients were recovered and the other 15(60%) were improved.The improved patients tended to have a higher peak ALT(808 ± 348 U/L vs 623 ± 118 U/L,P = 0.016) and shorter treatment duration before discharge(8 ± 6 d vs 28 ± 12 d,P = 0.008) compared with the recovered patients.Twenty-two drugs and 6 herbs were found associated with DILI.Antibacterials were the most common agents causing DILI in 8(32%) cases,followed by glucocorticoids in 6(24%) cases.Twenty-four(96%) cases received treatment of DILI with at least one adjunctive drug.Agents for treatment of DILI included anti-inflammatory drugs(e.g.,glycyrrhizinate),antioxidants(e.g.,glutathione,ademetionine 1,4-butanedisulfonate and tiopronin),polyene phosphatidyl choline and herbal extracts(e.g.,protoporphyrin disodium and silymarin).Diagnosis of DILI was not mentioned in the discharge letter in 60% of the cases.Relative to prevalent cases and cases from wards of internal medicine,incident cases and cases from surgical wards had a higher risk of missed diagnosis in discharge letter [odds ratio(OR) 32.7,95%CI(2.8-374.1),CONCLUSION:DILI is mostly caused by use of antibacterials and glucocorticoids,and constitutes about one fifth of hospitalized patients with ALT 10 ULN.DILI is underdiagnosed frequently.     

药物性肝损伤诊断进展

药物性肝损伤（DILI）是指在使用某一种或者几种药物后,由于药物本身或其代谢产物而引起的不同程度的肝损害。近年来,DILI的报道越来越多,但DILI症状发生率低,且缺乏特异性,易误诊。国内外DILI的诊断标准多样,对比各种诊断标准的优缺点,寻找最佳的诊断策略,对DILI的早期治疗和预后意义重大。     

Strategy for the control of drug-induced liver injury due to investigational treatments/drugs for COVID-19

Investigational treatments/drugs for coronavirus disease 2019 (COVID-19) have been applied, with repurposed or newly developed drugs, and their effectiveness has been evaluated. Some of these drugs may be hepatotoxic, and each monotherapy or combination therapy may increase the risk of drug-induced liver injury (DILI). We should aim to control dysregulation of liver function, as well as the progression of COVID-19, as much as possible. We discussed the potential risks of investigational treatments/drugs and promising drugs for both COVID-19 and DILI due to investigational treatments/drugs.