四川省医院药物性肝损害病例分析

目的 探讨药物性肝损害的病因、临床特点、过敏原检测、分型、治疗效果及预后分析.方法 选择四川省人民医院370例临床诊断为药物性肝损害的门诊及住院患者,对其用药史、临床表现、肝功能、过敏原检测及预后等进行回顾性分析.结果 引起药物性肝病的前3位药物分别为中草药(27.30％)、抗肿瘤药物(18.92％)、抗结核药物(13.78％);临床表现非特异.肝损害以肝细胞损害型最为常见(56.76％).过敏原IgE检测阳性率高达68.11％,高IgE提示过敏的可能性大.药物性肝损害患者的预后较好,其中治愈和好转率达85.95％.结论 引起药物性肝病的药物种类繁多,由于药物性肝病临床表现无特异性,易误诊及漏诊,因此在临床工作中应重视药物性肝损害,过敏原检测有一定临床意义.     

418例药物性肝损害临床特征及预后分析

目的分析引起药物性肝损害的药物种类,探讨其临床特征及预后。方法回顾性总结我院近3年收治的418例药物性肝损害患者临床资料,分析其药物种类、临床表现、肝脏生化学检测、肝穿刺病理及治疗转归等相关指标。结果引起药物性肝损害前5类药物分别是中药、抗生素、解热镇痛药、抗结核药、心血管药。418例患者中急性药物性肝损害218例(占52.2%);慢性药物性肝损害112例(占26.8%);药物性肝功能衰竭81例(占19.4%);药物性肝硬化7例(占1.7%)。418例药物性肝损害患者中治愈152例(36.4%),好转206例(49.3%),无效47例(11.2%),死亡13例(3.1%)。影响预后的肝功能指标为AST、TBil、Alb、CHE、PTA。结论药物性肝损害的的致病药物种类较多,临床表现缺乏特异性,AST、TBil、Alb、CHE、PTA与预后具有明显的相关性。     

药物性肝损害213例临床特点及诊治体会

目的分析药物性肝损害的病因、临床特点及预后,并评价治疗效果,以提高对药物性肝损害的认识,促进临床合理用药。方法回顾性分析2003年1月至2013年12月我院消化内科收治的213例急性药物性肝损害患者的基本情况、用药史及临床特点。结果引起药物性肝损害前4位的药物分别是非甾体类抗炎药(55例,占25.8%)、中草药(46例,占21.6%)、抗结核药(39例,占18.3%)和免疫抑制剂(29例,占13.6%)。发生药物性肝损害的最常见给药途径是口服(106例,51.2%)。主要临床表现为乏力、纳差、发热、恶心、黄疸、呕吐及腹部不适。肝损害以胆汁瘀积型最为常见。预后良好,显效率72.3%(154例),有效率21.6%(46例),总有效率为93.9%(200例)。结论引起药物性肝损害的药物种类繁多,临床表现无特异性,因此临床用药要严格把握用药指征,进而做到预防药物性肝损害的发生。     

药物性肝损害105例临床分析

药物性肝损害是常见的肝病之一 ,随着药物种类的不断增多及广泛应用于临床 ,药物性肝损害的发病率也相应增加。药物性肝损害的临床和病理变化多端 ,且临床表现和实验室检查无特异性 ,易被误诊。本文对 10 5例药物性肝损害进行了临床分析 ,以增强临床医师对药物性肝损害的认识。1　资料和方法1.1　一般资料　 1998- 0 1至 2 0 0 2 - 0 5收入我院共确诊为药物性肝病的患者共 10 5例 ,其中男性 4 7例 ,女性 5 8例 ,年龄为 15～ 80岁 ,平均年龄 (4 2 5 6± 13 75 )岁。1.2　诊断标准　 (1)有明确的服药史。 (2 )用药后数周至数月内出现肝损害的…     

药物性肝损害41例临床分析

目的分析药物性肝损害(DILI)的病因及临床特点,提高对药物性肝损害的认识。方法对本院41例药物性肝损害患者的临床资料进行回顾性分析,根据服药时间及服用药物种类、临床表现、肝损害的分型进行综合评价,总结药物性肝损害的临床特点。结果引起肝损害的药物前3名依次为:中草药及中成药14例(32.6%),抗生素10例(23.3%),降压药5例(11.6%)。临床分型:肝细胞损伤型13例,占31.7%;胆汁淤积型15例,占36.6%;混合型12例,占39.3%。结论临床上多种药物可导致肝损害,因此在使用有肝损害副作用药物时,应及时检测肝功能,以求早发现、早治疗。     

33例药物性肝病的临床分析

目的分析药物性肝病患者的病因及临床特点分析,以提高临床医生对该病的认识。方法采用回顾性分析对33例药物性肝病患者的用药史、临床表现、肝功能检查、病原学标志物以及治疗转归作综合判断。结果引起药物性肝病的相关药物有:抗菌素类药占36.3%(12/33),中药占15.2%(5/33),抗结核药占12.1%(4/33),抗肿瘤药占9.1%(3/33),解热镇痛药占12.1%(4/33),抗甲状腺药占6.1%(2/33),抗精神病药占3.0%(1/33),其它药物占6.1%(2/33)。临床表现为急性药物性肝病21例,慢性药物性肝病12例。临床表现依药物的作用机制而不同,患者主要表现为黄疸和转氨酶升高。经停药及护肝治疗预后良好。结论不同种类的药物均可能引起药物性肝病,应引起重视。     

药物性肝病122例临床分析

目的探讨引起药物性肝病的常见药物及临床特点。方法对本院近3年来收治的122例药物性肝病患者进行回顾性分析。结果①共12类药物与药物性肝病有关，前5位依次是抗结核药、中药、抗微生物药、抗肿瘤药及抗痛风药。②临床表现不同。③临床分型以急性多见，其中肝细胞损害型为49．6％。④停药后保肝治疗预后较好。结论药物性肝病是临床上较常见和易被忽视的疾病，应引起临床医生的重视。     

76例药物性肝病的临床特点分析

目的通过对药物性肝病的病因、临床特点及预后等分析,加深对药物性肝病的认识,为预防和早期治疗该病提供参考。方法采用回顾分析的方法对我院76例药物性肝病的住院患者进行研究。结果引起药物性肝病最主要的药物为中药制剂、抗结核药、抗生素、化疗药物、解热镇痛药及抗甲状腺功能亢进药物;一般在用药后1~4周内起病;临床主要表现以肝细胞型最为常见;早期发现后积极治疗多数预后良好;疗程3周至数月不等。结论药物性肝病尤其要注意中药制剂导致的肝病,主要以肝细胞型最为常见;早期发现、及时停用肝损害药物是治疗的前提;绝大部分药物性肝病预后良好,少数病例可发展为重症肝炎或肝硬化。     

58例药物性肝损害临床分析

目的对58例药物性肝损害进行临床分析,以指导今后药物性肝损害的诊断。方法采用Maria等提出的药物性肝损害诊断(评分)标准,回顾性分析我院1996年~2005年收治的符合标准的58例患者的用药史、症状、体征、实验室检查相关指标及出现异常时间和恢复时间。结果引起药物性肝损害的药物有9类,以抗生素类(27.6%)、皮肤科用药(20.7%)、中草药(12.1%)、抗结核药(8.6%)为主;临床上以肝细胞坏死型为主,表现以纳差、恶心、乏力多见,实验室检查以ALT、GGT升高多见,均在3个月内恢复。结论药物性肝损害临床表现和实验室检查无特异性,应提高对本病的认识,应用评分表法作出早期诊断。     

药物性肝病248例临床分析

目的分析药物性肝病(DILD)的病因、临床特点及预后,提高临床医生对DILD的诊疗水平。方法采用回顾性分析的方法对248例DILD住院患者的用药史、临床表现以及预后等进行研究。结果引起DILD的药物以抗生素类药物(12.1%)、中药(23.0%)、抗结核药物(8.0%)、抗肿瘤药物(7.2%)、免疫抑制剂(14.5%)为常见。临床表现以纳差(62.5%)、乏力(55.1%)、恶心(51.3%)、黄疸(37.2%)、腹痛(18.3%)、瘙痒(12.9%)、皮疹(4.6%)等多见;肝性脑病、腹水、凝血酶原时间、黄疸等因素与患者死亡相关。结论临床医生应重视和加强DILD的预防、诊断和治疗。     

101例药物性肝损伤患者的临床特征分析

目的:探讨药物性肝损伤(DILI)的临床特点及其规律,总结分析常见的致肝损伤药物。方法:回顾性分析101例DILI住院患者的临床资料。结果:101例DILI患者以肝细胞损伤型为主,占81.20%;胆汁淤积型肝损伤占3.00%,混合型肝损伤占15.84%。致肝损伤可疑药物前五位依次为中药(29.70%)、抗感染药(20.79%)、中成药(19.80%)、解热镇痛消炎药(8.91%)、泌尿系统药物(7.92%)。结论:DILI的临床特点与其他原因导致的肝损伤相似,可引起肝损伤的药物涉及临床各科,应予以重视。     

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。     

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.     

186例药物性肝损伤组织病理学及临床特征分析

目的探讨药物性肝损伤的组织病理学特点及临床特征,为早期诊治提供帮助。方法回顾性分析186例经肝活组织穿刺病理学诊断的药物性肝损伤患者的用药史、病理特点、临床表现、生化、血清学标志以及治疗转归等。结果引起药物性肝损伤前3位的药物是中药91例（49％）、抗生素41例（22％）、解热镇痛药23例（12．4％）;临床分类：药物性肝功能衰竭8例（4．4％）、急性药物性肝损伤93例（50％）、慢性药物性肝损伤83例（44．6％）、药物性肝硬化2例（1．1％）;临床分型：肝细胞损伤型98例（52．7％）、胆汁淤积型35例（18．8％）、混合型55例（29．6％）。病理学特征主要表现为：肝细胞坏死、汇管区扩大、肝细胞脂肪变性、汇管区或窦周混合炎细胞浸润、嗜酸性粒细胞浸润、肝细胞胆汁淤积、肝细胞凋亡、可见吞噬色素的Kuffer细胞。治愈79例（42．5％）,好转102例（54．8％）,无效5例（2．7％）。无一例患者死亡或病情恶化。结论引起药物性肝损伤的首位药物为中药,临床表现无特异性,但组织病理学改变有一定特征。     

Anticancer drugs are the first cause of drug-induced liver injury in a reference hospital

Drug-induced liver injury (DILI) is a challenging liver disorder for hepatologists. We aimed to assess the pattern and causes of DILI in a tertiary hospital. We registered prospectively all patients referred with suspicion of DILI from 2018 to 2023. A total of 106 patients fulfilled the diagnostic criteria (30 caused by paracetamol were excluded; total number 76). The pattern of liver injury was hepatocellular in 55 (72%). Drugs causing DILI were antineoplastic (26%), antibiotics (24%), analgesics (12%), and recreational drugs (9%). Regarding clinical outcomes, 39 (51%) required hospitalization and 7 (9%) underwent a liver transplantation or died from acute liver injury. We identified 126 additional patients with DILI due to immune check-point inhibitors who were not referred to a liver disease specialist. Antineoplastic drugs have become the first cause of DILI in hospitals. A multidisciplinary approach and specific educational tools to increase DILI awareness are needed among different specialists.     

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.     

老年药物性肝损伤的临床特点

目的探讨引起老年药物性肝损伤的药物种类、临床特点及防治原则。方法对2005年1月～2009年6月复旦大学附属华东医院160例发生药物性肝损害的老年住院病例临床资料进行回顾性分析。结果药物性肝损害患病率为3．17％（160／5047）;老年患者联合用药多,易出现肝损害,以心血管药物最多,构成比为25．6％（41／160）,其次是抗肿瘤药,构成比为21．9％（35／160）,再次是抗生素,构成比为18．1％（29／160）。主要临床症状为疲乏纳差、恶心呕吐,构成比为39．4％（63／160）,黄疸构成比为8．1％（13／160）,低热构成比为5．6％（9／160）,皮肤搔痒构成比为4．4％（7／160）,无症状者构成比为59．4％（95／160）。临床治愈率为71．3％。结论心血管药、抗肿瘤药和抗生素是引起老年药物性肝损害的常见药物。老年患者肝功能受损后大多无明显症状。老年人肝损伤与其肝药物代谢酶活性降低及长期联合用药有关。     

Drug-induced liver injury due to antibiotics

Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin–clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1–3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.     

中国老年人急性药物性肝损伤879例临床荟萃分析

目的 探讨分析我国老年人急性药物性肝损伤的发病特点及诊治策略.方法 以"药物性肝损"或"药物性肝病"和"老年"为检索词,检索中文数据库,提取符合标准的临床资料进行总结和分析.结果 符合纳入标准的文献14篇,共879例老年急性药物性肝损伤患者,男583例,女296例.主要临床表现依次为消化道症状(45.41%)、黄疸(34.58%)、乏力(25.48%)、纳差(21.84%)等,无症状者占35.04%.临床分型以肝细胞型最为多见(57.40%).有827例患者提供了用药信息,其中以抗生素(18.98%)、中草药(18.26%)、心血管类药物(17.90%)和抗肿瘤药物(11.61%)多见.774例患者提供了预后信息,临床治愈和好转率为89.41%.结论 正确认识和处理老年人急性药物性肝损伤,对改善患者预后,降低病死率具有重要而深远的意义.