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Drug-induced liver injury: Do we know everything? 被引量:14
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作者 Tamara Alempijevic Simon Zec Tomica Milosavljevic 《World Journal of Hepatology》 CAS 2017年第10期491-502,共12页
Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating th... Interest in drug-induced liver injury(DILI) has dramatically increased over the past decade, and it has become a hot topic for clinicians, academics, pharmaceutical companies and regulatory bodies. By investigating the current state of the art, the latest scientific findings, controversies, and guidelines, this review will attempt to answer the question: Do we know everything? Since the first descriptions of hepatotoxicity over 70 years ago, more than 1000 drugs have been identified to date, however, much of our knowledge of diagnostic and pathophysiologic principles remains unchanged. Clinically ranging from asymptomatic transaminitis and acute or chronic hepatitis, to acute liver failure, DILI remains a leading causes of emergent liver transplant. The consumption of unregulated herbal and dietary supplements has introduced new challenges in epidemiological assessment and clinician management. As such, numerous registries have been created, including the United States Drug-Induced Liver Injury Network, to further our understanding of all aspects of DILI. The launch of Liver Tox and other online hepatotoxicity resources has increased our awareness of DILI. In 2013, the first guidelines for the diagnosis and management of DILI, were offered by the Practice Parameters Committee of the American College of Gastroenterology, and along with the identification of risk factors and predictors of injury, novel mechanisms of injury, refined causality assessment tools, and targeted treatment options have come to define the current state of the art, however, gaps in our knowledge still undoubtedly remain. 展开更多
关键词 Acute liver failure Drug-induced liver injury Hepatoxicity Acetaminophen toxicity Cholestatic injury Liver biopsy PHARMACOEPIDEMIOLOGY herbal-induced liver injury Hy’s law
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Herbal and dietary supplement induced liver injury:Highlights from the recent literature 被引量:2
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作者 Stephanie M Woo William D Davis +3 位作者 Soorya Aggarwal Joseph W Clinton Sara Kiparizoska James H Lewis 《World Journal of Hepatology》 2021年第9期1019-1041,共23页
Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing S... Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows. 展开更多
关键词 herbal-induced liver injury Dietary supplement-induced liver injury Druginduced liver injury Roussel Uclaf Causality Assessment Method HEPATOTOXICITY Liver toxicity
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中药肝毒性评价的现状与挑战 被引量:10
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作者 李芝奇 赵霞 +5 位作者 徐玥 魏紫樱 马志强 吴怡青 赵崇军 林瑞超 《中华中医药杂志》 CAS CSCD 北大核心 2020年第10期4827-4835,共9页
目前中药由于其低毒有效的特征而逐步被世界所认可,但是中药不良反应事件,尤其是肝毒性事件的报道,严重影响了中药的现代化应用的进程。文章总结了中药在临床应用和临床前研究中所面临的主要问题,阐述了中药肝毒性机制以及中药肝毒性生... 目前中药由于其低毒有效的特征而逐步被世界所认可,但是中药不良反应事件,尤其是肝毒性事件的报道,严重影响了中药的现代化应用的进程。文章总结了中药在临床应用和临床前研究中所面临的主要问题,阐述了中药肝毒性机制以及中药肝毒性生物标志物筛选等方面的研究进展,讨论了中药肝损伤在临床上的关键特征和临床诊断中所面临的主要挑战,以期为未来中药肝毒性的研究提供参考。 展开更多
关键词 肝毒性 中药 中药不良反应与安全警戒 生物标志物 中草药致肝损伤
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五味子醇甲对千里光碱致小鼠肝损伤的改善作用 被引量:4
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作者 陈岩 贾夏丽 +3 位作者 熊爱珍 王长虹 杨莉 王峥涛 《药学学报》 CAS CSCD 北大核心 2022年第12期3626-3633,共8页
菊三七含千里光碱(senecionine, SEN)等大量吡咯里西啶生物碱(pyrrolizidine alkaloids, PAs),其所导致的肝毒性问题成为最受关注的中药药源性肝损伤之一,但尚无有效的临床治疗药物。本课题组前期研究表明CYP3A4抑制剂利托那韦可有效抑... 菊三七含千里光碱(senecionine, SEN)等大量吡咯里西啶生物碱(pyrrolizidine alkaloids, PAs),其所导致的肝毒性问题成为最受关注的中药药源性肝损伤之一,但尚无有效的临床治疗药物。本课题组前期研究表明CYP3A4抑制剂利托那韦可有效抑制SEN代谢活化并降低其肝毒性。保肝中药五味子含大量木脂素类活性成分,可通过影响药物代谢酶改善药源性肝损伤。因此,本研究探讨了五味子主要木脂素类化合物五味子醇甲(schisandrol A,SoA)对SEN致小鼠肝损伤的改善作用,并初步探讨其对千里光碱代谢的影响。所有动物实验经上海中医药大学实验动物伦理委员会审查(PZSHUTCM210604002),符合实验动物伦理相关规范。小鼠单次灌胃SEN (150μmol·kg^(-1))造成肝损伤模型,并设SoA (116μmol·kg^(-1))干预组、溶剂对照组和SoA对照组。结果表明, SoA可明显降低SEN致肝损伤小鼠血清转氨酶活性,缓解肝细胞坏死、肝窦淤血等病理状态。进一步测定小鼠血清中SEN代谢产物的含量,结合体外肝微粒体代谢研究,发现SoA可抑制SEN代谢活化关键酶CYP3A4酶活性,降低千里光碱代谢产物的含量。本研究表明, SoA可明显改善SEN致小鼠肝损伤,与抑制SEN代谢活化密切相关。研究结果为基于药物代谢探讨SEN的减毒策略,以及菊三七等含PAs中草药的临床合理应用提供理论依据。 展开更多
关键词 吡咯里西啶生物碱 千里光碱 木脂素 五味子醇甲 中药药源性肝损伤 CYP3A4
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药物性肝损伤诊治现状和进展 被引量:4
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作者 方志雄 张海明 陈军 《现代医药卫生》 2018年第13期1944-1948,共5页
药物性肝损伤(DILI)是临床上比较常见的不良反应,随着新药的不断研发与应用、大量保健品的滥用,DILI发病率呈逐年增加趋势。该文通过检索国内外最新发表文献,对DILI发生背景、临床表现与分型、诊断、预后的预测及治疗等方面进行了综述... 药物性肝损伤(DILI)是临床上比较常见的不良反应,随着新药的不断研发与应用、大量保健品的滥用,DILI发病率呈逐年增加趋势。该文通过检索国内外最新发表文献,对DILI发生背景、临床表现与分型、诊断、预后的预测及治疗等方面进行了综述,为临床医生诊断和治疗DILI提供参考。 展开更多
关键词 肝疾病 药用制剂 肝炎 中毒性 药物性肝损伤 中草药肝毒性
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泽泻水醇提取物改善千里光碱致小鼠急性肝损伤的作用与机制研究 被引量:9
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作者 姜凯元 叶铉玲 +4 位作者 熊芬 张祎 杨莉 熊爱珍 王峥涛 《药学学报》 CAS CSCD 北大核心 2021年第3期823-830,共8页
近年来,含吡咯里西啶生物碱(pyrrolizidine alkaloid,PA)的中草药所致药源性肝损伤引起了国内外的广泛关注,但缺乏有效的临床治疗药物。因此,本文研究中药泽泻对代表性PA千里光碱(senecionine,SEN)所致急性肝损伤的改善作用,并初步探讨... 近年来,含吡咯里西啶生物碱(pyrrolizidine alkaloid,PA)的中草药所致药源性肝损伤引起了国内外的广泛关注,但缺乏有效的临床治疗药物。因此,本文研究中药泽泻对代表性PA千里光碱(senecionine,SEN)所致急性肝损伤的改善作用,并初步探讨其潜在的药理作用机制。实验方案经上海中医药大学实验动物福利与伦理委员会审查,符合实验动物福利与伦理相关规范。小鼠单次灌胃SEN(50 mg·kg^(-1))造成急性肝损伤模型,并设泽泻水提物(18 g·kg^(-1))保护组、泽泻醇提物(18 g·kg^(-1))保护组和空白对照组。结果表明,泽泻对SEN致小鼠急性肝损伤有明显的保护作用:泽泻提取物可显著降低急性肝损伤小鼠血清谷丙转氨酶、谷草转氨酶活性及总胆汁酸水平,炎性细胞浸润、肝窦淤血、肝组织坏死等病理变化均有所缓解,且醇提物药效优于水提物。进一步测定血清中主要胆汁酸的含量和肝脏胆汁酸代谢相关因子的mRNA和蛋白表达,发现泽泻可调控胆汁外排转运体和肝脏代谢酶的表达,维护胆汁酸代谢平衡,修复受损的肝细胞。本研究为临床上应用泽泻防治PA致肝损伤提供了理论依据。 展开更多
关键词 泽泻 胆汁酸 吡咯里西啶生物碱 千里光碱 药源性肝损伤
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木瓜丸与追风透骨丸联用致肝损伤 被引量:1
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作者 徐智宇 张爱武 《药物不良反应杂志》 CSCD 2022年第4期223-224,共2页
1例63岁女性患者因腱鞘炎口服木瓜丸30丸、2次/d,追风透骨丸6 g、2次/d。服药10 d后,患者出现恶心、呕吐,并进行性加重;服药22 d后,患者发热、恶心、干呕、上腹轻度疼痛、全身浮肿、皮肤瘙痒,精神、食欲、睡眠状况不佳。实验室检查示丙... 1例63岁女性患者因腱鞘炎口服木瓜丸30丸、2次/d,追风透骨丸6 g、2次/d。服药10 d后,患者出现恶心、呕吐,并进行性加重;服药22 d后,患者发热、恶心、干呕、上腹轻度疼痛、全身浮肿、皮肤瘙痒,精神、食欲、睡眠状况不佳。实验室检查示丙氨酸转氨酶(ALT)454 U/L,天冬氨酸转氨酶(AST)946 U/L,碱性磷酸酶(ALP)133 U/L,γ-谷氨酰转移酶(γ-GT)170 U/L,直接胆红素(DBil)12.8μmol/L,谷氨酸脱氢酶17.3 U/L。实验室和影像学检查排除病毒性肝炎和胆道梗阻性疾病,诊断为药物性肝损伤。停用木瓜丸、追风透骨丸,给予复方二氯醋酸二异丙胺注射液、复方甘草酸苷片等治疗。患者肝功能逐步好转。12 d后,患者ALT 62 U/L、AST 49 U/L、γ-GT 38 U/L、DBil 7.2μmol/L。调整用药为复方甘草酸苷3片、3次/d(服药2周)。4周后复查,患者ALT 31 U/L,AST 26 U/L,γ-GT 30 U/L,DBil 5.0μmol/L。 展开更多
关键词 中草药 化学和药物性肝损伤 乌头属
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