FACTORS ASSOCIATED WITH CHRONIC HEPATITIS C INFECTION

与慢性丙型肝炎感染相关的因素

• 批准号: 7381031
• 负责人: CARLOS A SARIOL
• 金额: $ 6.07万
• 依托单位: UNIVERSITY OF PUERTO RICO MED SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381031
• 关键词: FACTORS; ASSOCIATED; CHRONIC; HEPATITIS; INFECTION

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. The mechanism of liver damage in chronic hepatitis C (CHC) infection remains unclear. Recent studies have supported the role of immune response mechanism in liver injury of CHC infection. The association of the serum level of specific cytokines or the presence of cytokine gene polymorphisms with the evolution to CHC and development of liver damage have been studied before. High levels of T-helper 2 (Th2) cytokines in serum have been associated with the development of chronic liver damage. Growth factor genes such as tumor necrosis factor alpha (TNF-a) and TNF-b, and a variable polymorphism in cytokines have also been associated with liver damage. The impact of viral genotypes is less clear. However, there is no available data where all these factors have been analyzed in the same group of patients. In addition, much data has been collected from patients of Caucasian or African American origin but there is a gap of information in patients with a Hispanic background. The AIMS of this proposal are to: 1. Determine the viral genome diversity in patient with CHC showing varying stages of liver damage. 2. Determine the serum profile of Th 1 (TNF-a, INF-g) and Th 2 (IL-10, IL-4) cytokines in patient with CHC showing varying stages of liver damage. 3. Determine the polymorphism in Th1 (TNF-a, INF-g) and Th2 (IL-10) cytokine genes in patient with CHC showing varying stages of liver damage. The preliminary results of this pilot study will help us to design a further and more extensive study including more patients and the study of more factors affecting the development of HCV-induced chronic liver damage. These specifics AIMS will help us to understand the contribution of both viral and genetic factors to the development of chronic liver damage in a population with a Hispanic genetic background. In the future it might provide new arguments to support the development of new therapeutic or prophylactic approaches. Patients will be selected from the GI and Hepatology outpatient and research clinics affiliated with the UPR School of Medicine. Eligible candidates must be within 21 to 65 years of age and be Puerto Rican or of first degree Puerto Rican descent. Eligible patients must have serological evidence of hepatitis C virus RNA and liver biopsy at the time of evaluation Patients who have other concomitant etiologies known to cause chronic liver disease will be excluded. Patients who received any hepatitis C treatment cannot be considered for this study. Other exclusion criteria include HIV positivity, active IV drug use within 6 mo. prior to study entry, past history or current alcohol abuse defined as 24 g/d in males and 16 g/d in females, history of autoimmune disease, history of NSAID¿s, steroids, or immunomodulator use within 6 mo. prior to study entry, history of mild infectious process 3 mo. prior to entry, severe infectious process 6 months prior to study initiation or surgical procedure within 6 mo. prior entry. Hepatitis C negative controls will be recruited for this study and will also be selected at the RCM GI outpatient clinics. Controls must be Puerto Rican or Puerto Rican descent and 21 to 65 years of age. Controls will be required to meet clinical exclusion criteria. After initial clinical eligibility is confirmed, hepatitis C and HIV negativity will be confirmed serologically prior to final eligibility confirmation. After obtaining informed consent, demographic and medical data will be collected from all subjects and blood will be drawn (approx 20 cc in all patients). Baseline liver biopsies will be examined in order to establish the pathological stage of fibrosis using the METAVIR System. Patients having fibrosis stage of F0 to F2 will be stratified into Group 1 and those with fibrosis stage F3 to F4 will be stratified into Group 2. A total of 30 patients will be stratified and selected so that 15 patients are participating in each group.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。列出的是该中心，不一定是研究者的机构。 最近的研究支持免疫反应机制在 CHC 感染的肝损伤中的作用。血清关联之前已经研究过特定细胞因子的水平或细胞因子基因多态性的存在与 CHC 的演变和肝损伤的发展有关，血清中高水平的 T 辅助细胞 2 (Th2) 细胞因子与慢性肝损伤的发展有关。肿瘤坏死因子 α (TNF-a) 和 TNF-b 等生长因子基因以及细胞因子的可变多态性也与肝损伤有关。但病毒基因型的影响尚不清楚。全部此外，还从白种人或非裔美国人血统的患者中收集了许多数据，但在西班牙裔背景的患者中存在信息空白。该提案的目的是： 1. 确定显示不同阶段肝损伤的 CHC 患者的病毒基因组多样性 2. 确定 Th 1 (TNF-a、INF-g) 和 Th 2 (IL-10、IL-4) 细胞因子的血清谱。患者有3. 确定不同阶段肝损伤的 CHC 患者 Th1（TNF-a、INF-g）和 Th2（IL-10）细胞因子基因的多态性 本试验的初步结果。研究将帮助我们设计一项进一步、更广泛的研究，包括更多的患者和更多影响丙型肝炎病毒引起的慢性肝损伤发展的因素的研究，这些具体目标将帮助我们了解病毒和遗传因素对肝损伤的影响。慢性肝脏的发展未来，它可能会为支持新的治疗或预防方法的开发提供新的论据，患者将从 UPR 医学院附属的胃肠病学和肝病学门诊和研究诊所中选择。符合资格的候选人必须年龄在 21 至 65 岁之间，并且是波多黎各人或波多黎各一级血统。 符合资格的患者在评估时必须有丙型肝炎病毒 RNA 和肝活检的血清学证据。患有其他已知导致慢性肝病的病因的患者将被排除在外。接受过任何丙型肝炎治疗的患者不能被考虑参加本研究。或目前的酒精滥用定义为男性 24 克/天，女性 16 克/天，自身免疫性疾病史，NSAID 病史¿入组前 6 个月内使用过类固醇或免疫调节剂，入组前 3 个月内有过轻度感染史，入组前 6 个月内有过严重感染史或入组前 6 个月内接受过手术。本研究将招募对照者，并且还将在 RCM GI 门诊诊所中进行选择。对照者必须是波多黎各人或波多黎各血统，并且要求对照者年龄在 21 至 65 岁之间，以满足临床排除的要求。初步临床资格得到确认后，在最终资格确认之前，将通过血清学方法确认丙型肝炎和艾滋病毒阴性。在获得知情同意后，将从所有受试者中收集人口统计和医疗数据，并抽取血液（总共约 20 毫升）。将使用 METAVIR 系统检查基线肝活检以确定纤维化的病理阶段，将纤维化阶段为 F0 至 F2 的患者分为第 1 组和第 1 组。纤维化阶段F3至F4将被分层到第2组。总共30名患者将被分层和选择，以便每组15名患者参与。