药物性肝损害40例临床分析

目的提高对药物性肝损害的认识。方法对2003年4月～2007年7月住我院的40例药物性肝损害患者进行回顾性分析,对患者的一般资料、临床表现、实验室检查结果及涉及的药物进行总结。结果女性22例,男性18例。潜伏期多为1～8w。临床分型:肝细胞型24例(60.0%),胆汁淤积型5例(12.5%),混合型11例(27.5%),肝细胞型是最常见的临床类型。由西药引发肝损害27例(67.5%),中药9例(22.5%),多种药物(如中药 西药,成分不详的减肥药)4例(10.0%)。临床治愈34例(85.0%),好转4例(10.0%),死亡2例(5.0%)。结论多种药物均可引起药物性肝损害,应予以重视,临床上以肝细胞型为主,经积极治疗多数预后良好。     

药物性肝损害38例临床分析

<正>随着临床药物种类的增加,引起药物性肝炎的药物种类也越来越多,药物性肝损害的发生在逐年增加,本文对我科2005年1月至2008年8月收治的38例药物性肝炎进行综合分析,现报告如下。     

696例药物性肝损害药物的临床分析

近年来随着临床药物种类的迅速增多和药物治疗的增加,非处方药物范围的不断扩大及患者自行服药的机率增加,药物性肝损害的发生率正在逐年增多[1]。我们研究了我院1994年至2006年住院的696例药物性肝损害患者的损肝药物、药物变迁及年发病率,并总结分析其临床特点。     

药物性肝损害162例临床分析

目的探讨药物性肝损害发生机制及防治措施。方法回顾性分析162例药物性肝损害患者的年龄、损肝药物、临床表现、治疗及转归。结果导致肝损害的药物常见的有利福平（17．3％,28／162）、消渴丸（16．7％,27／162）、非诺贝特（9．9％,16／162）、白癣皮（8．6％,14／162）及环磷酰胺（7．4％,12／162）等;药物性肝病临床表现为纳差、乏力、恶心、呕吐、皮肤黄疸等;治疗后158例治愈,1例好转,3例死亡。结论使用可能损肝的药物时应加强监测,定期复查肝功能。     

浅述药物性肝损害

随着新药的不断开发应用及联合用药的增多,药物性肝损害的发生率不断增加,引起人们对药物性肝损害重视及研究。目前研究人员在药物性肝损害遗传学、蛋白质组学等方面的研究取得了较大进展。现就引起肝损害的药物、发病机制、预防及治疗等加以综述。     

药物性肝损害36例临床分析

目的提高对药物性肝损害诊断的准确性。方法对36例药物性肝损害（DILI）患者的临床资料进行回顾性分析。结果在药物性肝损害患者中，中药9例（25％），居首位，其次为抗生素7例（19.4％）和抗结核药物6例（16．7％）。临床主要表现为皮肤巩膜黄染（55．6％）、乏力（47.2％）、纳差（44．4％）；其中肝细胞损伤型22．2％，胆汁淤积型66．7％，混合型11．1％．结论药物性肝损害是临床常见病，应重视中药的肝毒性，提高对药物性肝损害的识别，尤其应重视胆汁淤积型肝病的鉴别诊断。     

药物性肝损害病例分析

近年来药物性肝损害（DILI）的发生率不断上升,为探讨其病因、类型及临床特征,回顾性总结了4例药物性肝损害患者的临床资料,对损肝药物、临床特点及并发症等方面进行分析,为临床药物性肝损害的防治提供参考。     

抗结核药物性肝损害研究进展

含有异烟肼、利福平、毗嗪酰胺的6个月短程化疗是结核病控制的主要策略.但异烟肼、利福平、毗嗪酰胺均有潜在的肝毒性,均可导致药物性肝损害的发生,常常导致患者依从性下降,导致结核病治疗失败.本文就抗结核药物肝损害的发生率、病理学特征、临床表现、发病机制、危险因素和防治等方面进行综述.     

抗结核药致药物性肝损害的临床分析

抗结核药所致的药物性肝损害是结核病治疗过程中常遇到的问题,不但会影响结核病的治疗,而且严重时会直接危及患者生命。现将我院2005—2006年住院的结核病患者,在抗结核治疗过程中发生的药物性肝损害进行分析。     

药物性肝损害48例临床分析

本文对2004年1月至2008年12月收治的48例药物性肝损害进行综合分析,现报告如下。1资料和方法1．1一般资料：48例患者中．男性17例,女性31例,年龄18-73岁,平均（41&#177;13）岁。根据服药史、临床表现、血常规、肝功能、各种肝炎病毒血清标志物及停药后治疗效果做出综合判断。     

药物性肝炎临床研究

目的:分析56例药物性肝炎患者的病因及临床特点,以提高对该病的认识.方法:采用回顾性分析,对56例药物性肝炎住院患者的用药史、临床表现、肝功能检查、病原学标志物以及治疗转归等进行综合分析.结果:引起肝损害的药物中抗结核类药占26.79%,抗生素类药占21.43%,抗肿瘤类药占14.29%,中草药占12.50%,抗甲状腺类药占8.93%,降血脂类药占7.14%,糖尿病类药占5.36%,其他占3.57%.结论:(1)引起药物性肝炎的药物种类繁多,以抗结核药、抗肿瘤药、抗生素类药及中草药多见.(2)药物性肝炎临床表现与普通病毒性肝炎无明显特异性.(3)药物性肝炎肝功能检查显示GGT及ALP明显升高,可作为鉴别诊断的参考依据之一.     

药物性肝损害103例临床分析

目的：探讨药物性肝损害的临床特点及其发病规律。方法：对103例药物性肝损害的临床资料进行回顾性分析。结果：药物性肝损害占同期“急性肝炎”住院患者的9.6%;引起肝损害的药物种类繁多,以抗结核药为最多（45％）,其次为中药（20％）;用药2－4wk出现肝损害者最常见（66％）,2wk内者次之（26.2%);临床以急性肝炎肝细胞型最常见（62.1%),其中5例出现暴发性肝功能衰竭（4.9%);主要临床表现为疲乏、纳差、恶心、呕吐、腹胀（71.8%),其次为黄疸（59.2%),肝功能受损以ALT、GGT、BIL增高为主;临床治愈65例（63.1%),好转34例（33％）,死亡3例（2.9%)。结论：药物性肝损害的临床特点并无特异性,与病毒性肝炎相似;可引起肝损害的药物包括临床各科应用的药物,以往认为比较安全的中药,肝损害发生率逐渐增多,达20％,值得重视。     

儿童急性白血病化疗药物性肝损害的临床分析

目的探讨儿童急性白血病化疗药物性肝损害的临床特点。方法回顾性分析2007年1月至2008年12月间在本院儿科血液区住院的50例儿童急性白血病药物性肝损害患者的相关特点。结果全部病例均为急性肝损害,发生在用药后2～21d。临床分型：肝细胞型29例;混合型12例;胆汁淤积型9例。引起肝损害的药物：MTX相关23例（46%）,MTX与6MP合用所致15例（30%）,L-ASP引起者5例（10%）,Ara-c引起1例（2%）,多药物综合作用6例（12%）。治疗及转归：停药或减量用药;并给予保肝、降酶、退黄治疗,本组患者均治愈。结论儿童急性白血病化疗药物性肝损害以急性肝损害常见,肝损害临床表现各异,与药物有关。早期发现及停药是治疗药物性肝损害的关键。     

Mechanisms of immune checkpoint inhibitor-mediated liver injury

The immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1/ligand-1 (PD-1/PD-L1) are vital contributors to immune regulation and tolerance. Recently immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, they come with the cost of immune related adverse events involving multiple organs such as the liver. Due to its constant exposure to foreign antigens, the liver has evolved a high capacity for immune tolerance, therefore, blockade of the immune checkpoints can result in aberrant immune activation affecting the liver in up to 20% of patients depending on the agent(s) used and underlying factors. This type of hepatotoxicity is termed immune mediated liver injury from checkpoint inhibitors (ILICI) and is more common when CTLA4 and PD-1/PD-L1 are used in combination. The underlying mechanisms of this unique type of hepatotoxicity are not fully understood; however, the contribution of CD8⁺ cytotoxic T lymphocytes, various CD4⁺ T cells populations, cytokines, and the secondary activation of the innate immune system leading to liver injury have all been suggested. This review summarizes our current understanding of the underlying mechanisms of liver injury in immunotherapy using animal models of ILICI and available patient data from clinical studies.     

药物性肝损害的临床分析

目的：指导临床医生合理用药和及时、正确诊治药物性肝损害。方法：对2002年我院住院病人住院期间肝功能指标发生异常的205例病例进行回顾性调查分析。结果：205例中药物性肝损害48例，涉及药物10类、28种，依次为抗肿瘤药、抗生素、降血脂药、降糖药及激素类药，肝损害类型呈多样性。结论：药物性肝损害是临床上较常见和易被忽视的疾病，应引起临床医务工作者的重视。     

The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice

Antitubercular drugs have been known to be potentially hepatotoxic and may lead to drug-induced liver injury. In this study, we aimed to investigate the protective effects of ursodeoxycholic acid (UDCA) on liver injury caused by co-administration with isoniazid and rifampicin, two famous antitubercular drugs. Liver injury was induced by co-treatment with isoniazid (75 mg/kg) and rifampicin (150 mg/kg) for one week. Mice were orally administered with UDCA (15, 50 and 150 mg/kg) 30 min before isoniazid and rifampicin. We show that serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were significantly increased in mice treated with isoniazid plus rifampicin. An obvious fatty accumulation, accompanied by mild necrosis and inflammation, was observed in liver of mice treated with rifampicin plus isoniazid. In addition, isoniazid plus rifampicin resulted in hepatic apoptosis, as determined by terminal dUTP nick-end labeling (TUNEL) staining and caspase-3 activation. Additional experiment showed that isoniazid plus rifampicin significantly increased the level of hepatic malondialdehyde (MDA) and caused glutathione (GSH) depletion and 3-nitrotyrosine (3-NT) residues in liver. UDCA pretreatment significantly attenuated isoniazid plus rifampicin induced oxidative stress in liver. Importantly, UDCA pretreatment significantly alleviated isoniazid plus rifampicin induced hepatic apoptosis. Moreover, UDCA-mediated anti-apoptotic effect seemed to be associated with its regulation of Bcl-2 and Bax gene expression in liver. These findings suggest that UDCA might protect against isoniazid and rifampicin induced liver injury through its anti-oxidative and anti-apoptotic effects.     

Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity

The nonsteroidal antiinflammatory drug diclofenac causes rare but significant cases of serious hepatotoxicity, typically with a delayed onset (>1-3 months). Because there is no simple dose relationship and because liver injury cannot be reproduced in current animal models, individual patient-specific susceptibility factors have been evoked to account for the increased risk. While these patient factors have remained undefined, a number of molecular hazards have been characterized. Among these are metabolic factors (bioactivation by hCYP2C9 or hCYP3A4 to thiol-reactive quinone imines, activation by hUGT2B7 to protein-reactive acyl glucuronides and iso-glucuronides, and 4'-hydroxylation secondary to diclofenac glucuronidation), as well as kinetic factors (Mrp2-mediated concentrative transport of diclofenac metabolites into bile). From the toxicodynamic view, both oxidative stress (caused by putative diclofenac cation radicals or nitroxide and quinone imine-related redox cycling) and mitochondrial injury (protonophoretic activity and opening of the permeability transition pore) alone or in combination have been implicated in diclofenac toxicity. In some cases, immune-mediated liver injury is involved, inferred from inadvertent rechallenge data and from a number of experiments demonstrating T cell sensitization. Why certain underlying diseases (e.g., osteoarthritis) also increase the susceptibility to diclofenac hepatotoxicity is not clear. To date, cumulative damage to mitochondrial targets seems a plausible putative mechanism to explain the delayed onset of liver failure, perhaps even superimposed on an underlying silent mitochondrial abnormality. Increased efforts to identify both patient-specific risk factors and disease-related factors will help to define patient subsets at risk as well as increase the predictability of unexpected hepatotoxicity in drug development.     

Lipopolysaccharide exposure augments isoniazide‐induced liver injury

Isoniazide (INH) is a classic antituberculosis drug associated with clinical idiosyncratic drug‐induced liver injury. It has been hypothesized that the interaction between a drug and modest inflammation results in a decreased threshold for drug toxicity. In this study, we tested the hypothesis that INH causes liver injury in rats when coadministered with lipopolysaccharide (LPS). Neither INH nor LPS alone caused liver injury. The coadministration of INH and LPS was associated with increases in serum and histopathological markers of liver injury. Tumour necrosis factor‐α expression was significantly increased in the coadministered group. The downregulation of the bile acid transporter, bile salt export pump, and multidrug resistance protein 2 at both mRNA and protein levels was observed. Furthermore, the level of Farnesoid X receptor, which regulates the bile salt export pump and multidrug resistance protein 2, were clearly decreased. These results indicate that the coadministration of nontoxic doses of LPS and INH causes liver injury; the disruption of biliary excretion is considered the primary inflammation‐related characteristic of INH‐induced hepatotoxicity. Copyright © 2014 John Wiley & Sons, Ltd.