Drug Induced Hepatotoxicity During Viral Hepatitis

病毒性肝炎期间药物引起的肝毒性

• 批准号: 8100454
• 负责人: Yonas Getachew
• 金额: $ 14.27万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100454
• 关键词: Acetaminophen; Acute; Acute Hepatitis; Address; Adenovirus Infections; Adenoviruses; Aftercare; Antiviral Agents; Area; Autoimmune Process; Award; Basic Science; Biology; C57BL/6 Mouse; Chemicals; Chronic; Chronic Disease; Chronic Hepatitis; Chronic viral hepatitis; Coculture Techniques; Complication; Cytochrome P450; Cytokine Receptors; Defect; Development Plans; Down-Regulation; Drug Prescriptions; Environment; Enzymes; Gastroenterologist; Gene Expression; Glutathione; Goals; Hepatic; Hepatitis; Hepatitis C virus; Hepatocyte; Hepatotoxicity; Immune; Immune response; Immunology; In Vitro; Infection; Inflammatory; Injury; Interferons; Internal Medicine; Laboratories; Liver; Liver diseases; Lymphocyte; Measures; Mediating; Medical center; Mentors; Messenger RNA; Mus; Patients; Pharmaceutical Preparations; Physicians; Play; Predisposition; Proteins; Public Health; Research; Research Personnel; Risk; Role; Symptoms; Techniques; Testing; Texas; Time; Toxic effect; Training; Universities; Viral hepatitis; Virus Diseases; Work; Xenobiotic Metabolism; adduct; career; career development; clinical application; cohort; cytokine; cytotoxic; drug metabolism; enzyme activity; hepatoma cell; improved; in vivo; interest; intrahepatic; liver infection; mouse model; outcome forecast; public health relevance; response

DESCRIPTION (provided by applicant): I am an academic gastroenterologist/hepatologist in the department of Internal Medicine at the University of Texas Southwestern Medical Center. My long-term goal is to develop an independent career as a physician investigator, bridging the gap between basic science applications and clinical issues. I am interested in viral hepatitis and its acute and chronic impact on the liver. I am especially interested in the changes the liver undergo in P450 enzyme expression during viral hepatitis and the ultimate change in livers capacity to metabolize medications. I developed an interest in hepatitis as an internal medicine resident when I had a chance to work with large HCV patients in San Antonio, Texas. My proposed career development plan provides further training in this area in a closely mentored environment under the guidance of Dr. Dwain Thiele, Dr. Richard Auchus and Dr. Andrew Feranchack who are experts in liver immunology, Cytochrome P450 biology and hepatocyte biology respectively. The current proposed research focuses on understanding the cellular and chemical changes in the liver in the setting of acute and chronic hepatitis. During the time that I am supported by this K08 award I will obtain additional training in laboratory techniques and investigate questions relevant to the study of drug and xenobiotics metabolism in the liver. At the end of the proposed studies I hope to improve understanding of the impact of acute and chronic liver infection on hepatic cytochrome P450 enzyme activity and ultimately the ability of chronically infected livers to handle different medications. Understanding the interactions between cytochrome P450 expected intrahepatic immune responses and will also help us to understand changes in drug metabolism likely to occur during autoimmune inflammatory liver diseases. PUBLIC HEALTH RELEVANCE: Chronic and acute viral hepatitis have become major public health concern. Patients with acute viral hepatitis prodrome are inclined to take over the counter remedies to alleviate their symptoms. This work will try to shade some understanding to the potential interactions, problems, risks, and/or lack there of, between acute viral hepatitis and medications such as acetaminophen (APAP).

描述（由申请人提供）： 我是德克萨斯大学西南医学中心内科学系的学术胃肠病学家/肝病学家。我的长期目标是发展独立的职业作为医生研究者，弥合基础科学应用和临床问题之间的差距。我对病毒肝炎及其对肝脏的急性和慢性影响感兴趣。我对病毒性肝炎期间P450酶表达的肝脏发生的变化以及肝脏代谢能力的最终变化的变化特别感兴趣。当我有机会与德克萨斯州圣安东尼奥市的大型HCV患者一起工作时，我对肝炎作为居民产生了兴趣。在Dwain Thiele博士，Richard Auchus博士和Andrew Feranchack博士的指导下，我提出的职业发展计划在肝脏免疫学，细胞色素P450生物学和肝细胞生物学方面提供了进一步的培训。当前提出的研究重点是了解急性和慢性肝炎的肝脏的细胞和化学变化。在我获得该K08奖的支持期间，我将获得实验室技术的额外培训，并研究与肝脏中药物和异种生物代谢有关的问题。在拟议的研究结束时，我希望能够提高人们对急性和慢性肝感染对肝细胞色素P450酶活性的影响，并最终最终具有慢性感染肝脏处理不同药物的能力。了解细胞色素P450预期的肝内免疫反应之间的相互作用，还将帮助我们了解自身免疫性炎性肝疾病期间可能发生的药物代谢的变化。 公共卫生相关性： 慢性和急性病毒肝炎已成为主要的公共卫生问题。急性病毒肝炎的患者倾向于接管反疗法以减轻其症状。这项工作将试图在急性病毒肝炎和药物（例如对乙酰氨基酚（APAP））之间的潜在相互作用，问题，风险和/或缺乏的潜在相互作用，问题，风险和/或缺乏理解。