IMPACT OF CHRONIC VIRAL HEPATITIS ON PT D/C OF TX FOR LATENT TB-STUDY 26A (HIV)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：评估慢性病毒性肝炎与因肝毒性而永久停止治疗潜伏性结核病感染(LTBI)之间的关系。次要目标是：描述慢性病毒性肝炎与因肝毒性而暂时停止治疗的LTBI之间的关系；描述HIV感染与在LTBI治疗期间需要停止治疗的肝毒性(在已知HIV血清学状态的患者中)的相关性；描述在LTBI的治疗期间与需要停止治疗的肝毒性相关的艾滋病毒和丙型肝炎之间的协同作用；以及比较与酒精滥用、慢性病毒性肝炎和/或HIV感染相关的LTBI治疗期间需要停止治疗的肝毒性发生的时间。 研究计划：病例在达到病例研究定义的四周内，将接受关于慢性病毒性肝炎的知情同意程序和咨询，回答关于酒精和伴随药物摄入的简短问卷，并抽血筛查急性和慢性病毒性肝炎。这将需要在一个标准的红色顶管或分离管中收集5到10毫升的血液，用于储存和运输到疾控中心。这根管子是当地临床医生正在进行的任何测试之外的补充。同意参加次级研究的控制组将不迟于第8周的研究访问进行知情同意过程。在第8周的常规研究访问中，他们将接受关于慢性病毒性肝炎的咨询，回答关于酒精和伴随药物摄入的简短问卷，并抽血筛查急性和慢性病毒性肝炎。 方法：研究设计为26号研究参与者中的病例队列研究，比较两种治疗方案对潜伏性结核病感染的疗效。病例是临床试验参与者，持有研究药物(S)任何时间，与以下情况有关：(1)AST大于或等于正常上限(ULN)3和肝炎症状或体征；或(2)AST大于5ULN并有或没有肝炎症状或体征，并同意参加此子研究。参加第26项研究的5.5%的患者在参加母体研究时，将被随机选择作为子研究的潜在对照。 临床相关性：初步数据表明，慢性病毒性肝炎患者，无论是否合并艾滋病毒感染，在接受抗结核药物治疗期间，比那些没有慢性病毒性肝炎的患者经历更多的肝毒性。目前美国结核病控制的重点是扩大靶向结核菌素检测和治疗潜伏的结核病感染，这将使患有慢性病毒性肝炎的人群面临这一潜在风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The primary objective is to evaluate the association between chronic viral hepatits and permanent discontinuation of treatment for latent TB infection (LTBI) due to hepatotoxicity. Secondary objectives are: to describe the association between chronic viral hepatitis and temporary discontinuation of treatment for LTBI due to hepatotoxicity; to describe the association of HIV infection with hepatotoxicity requiring treatment discontinuation during treatment for LTBI (among the subset of patients with known HIV serostatus); to describe the synergism between HIV and HCV infection associated with hepatotoxicity requiring treatment discontinuation during treatment for LTBI; and to compare the time to onset of hepatotoxicity requiring treatment discontinuation during treatment for LTBI that is associated with alcohol abuse, chronic viral hepatitis, and/or HIV infection. RESEARCH PLAN: Cases, within four weeks of the time they fulfill the study definition of a case, will undergo the informed consent process and counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. This will require 5 to 10 cc of blood to be collected in one standard red top tube or separator tube, for storage and shipping to CDC. This tube is in addition to any testing the local clinician is conducting. Controls who agree to participate in the sub-study will undergo the informed consent process no later than the Week 8 study visit. At the Week 8 routine study visit, they will undergo counseling regarding chronic viral hepatitis, answer a brief questionnaire regarding alcohol and concomitant medication intake, and have blood drawn for screening for acute and chronic viral hepatitis. METHODS: The study design is a case-cohort study within enrollees in Study 26, which compares the efficacy of two treatment regimens for latent TB infection. A case is a clinical trial participant in either treatment arm who has study drug(s) held for any length of time associated with: (1) AST greater than or equal to 3 the upper limit of normal (ULN) and symptoms or signs of hepatitis; or (2) AST greater than 5 ULN with or without symptoms or signs of hepatitis, and who consents to be in this sub-study. Five and one-half percnt of patients enrolling in Study 26 will be randomly selected as potential controls for the sub-study at the time of enrollment in the parent study. CLINICAL RELEVANCE: Preliminary data suggst that persons with chronic viral hepatitis, with or without HIV co-infection, experience more hepatotoxicity during treatment with anti-tuberculosis drugs than do those without chronic viral hepatitis. The current U.S. TB control emphasis on expanding targeted tuberculin tesing and treatment of latent TB infection will expose populations with chronic viral hepatitis to this potential risk.