HCV & ALCHOOL-- EPIDEMIOLOGY & HOST-VIRUS CORRELATES

丙型肝炎病毒

• 批准号: 6213944
• 负责人: MARION G PETERS
• 金额: $ 22.13万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6213944
• 关键词: alcoholic beverage consumption; alcoholic hepatitis; alcoholic liver cirrhosis; alcoholism /alcohol abuse; biopsy; blood chemistry; chronic disease /disorder; clinical research; cytokine; drug /alcohol abstinence; helper T lymphocyte; hepatitis C virus; human subject; immune tolerance /unresponsiveness; interview; liver disorder; longitudinal human study; monocyte; pathologic process; questionnaires; substance abuse epidemiology; virus RNA; virus infection mechanism

Alcohol and hepatitis C virus (HCV) infection are recognized as independent causes of chronic liver disease and cirrhosis. Further, significant alcohol ingestion, defined variably as >30 gnvday (women) or >50-60 grnlday (men) has been associated with more severe histological disease, including cirrhosis and hepatocellular carcinoma and an accelerated rate of disease progression in patients with chronic HCV infection. The effect of more limited alcohol intake or non-daily drinking patterns on the progression of HCV disease are not known. In this study, we will establish a prospective cohort of at least 550 HCV-infected patients who drink varying amounts of alcohol at study entry. Total lifetime alcohol intake, patterns of alcohol ingestion, and periods of abstinence will be ascertained using validated questionnaires (Skinner, 1979; Russell, 1991) at study entry and annually for four years. Additional data collected at study entry include demographic, epidemiological and dietary history (including duration of HCV infection, mode of acquisition, use of iron supplements). A comprehensive evaluation of HCV RNA including viral titer in serum, liver and peripheral blood mononuclear cells (PBMCs), and baseline quasispecies complexity, will be obtained. Subjects with an alcohol intake of >30 gm/day (females) or >60 gm/day (males) will be counseled to completely abstain. A subset of 150 subjects drinking <15 gm/day (females) or <30 gm/day (males) of alcohol will be randomized to abstinence or no change in alcohol intake (control group). Annually we will readminister an alcohol questionnaire (12-month quantity/frequency questionnaire, National Alcohol Survey) and perform tests for ferritin, transfenin saturation, and serum aminotransferase activity. HCV viral quasispecies variability (assessed by heteroduplex mobility assay) HCV RNA quantitation and cytokine profiles will be compared in different tissue sources (serum, PBMCs and liver). Liver biopsies will be obtained at baseline and at the end of 4 years follow-up to assess severity and progression of liver disease. This study will determine 1) the quantity and pattern of alcohol intake associated with progression of HCV liver disease; 2) whether abstinence from alcohol among "moderate" or "light" drinkers reduces the rate of HCV disease progression; and 3) the host (including proinflammatory or profibrotic host genes which may be activated in the presence of alcohol) and viral factors (including quasispecies heterogeneity which may be altered by alcohol ingestion) which underlie the enhanced rate of disease progression in HCV-infected patients using alcohol.

酒精和丙型肝炎病毒（HCV）感染被认为是独立的 慢性肝病和肝硬化的原因。此外，大量酒精 摄入，定义为> 30 gnvday（女性）或> 50-60 grnlday（男性） 与更严重的组织学疾病有关，包括肝硬化和 肝细胞癌和疾病进展的加速率 患有慢性HCV感染的患者。饮酒摄入量更多的效果 或关于HCV疾病进展的非每日饮酒模式不是 已知。在这项研究中，我们将建立至少550的前瞻性队列 在研究入口时，HCV感染的患者喝了不同量的酒精。 总终生酒精摄入量，饮酒方式和周期 将使用经过验证的问卷来确定禁欲（Skinner，1979; Russell，1991年）在研究入学时，每年四年。其他数据 研究入口收集的包括人口统计学，流行病学和饮食 病史（包括HCV感染的持续时间，获取方式，使用铁 补充）。对HCV RNA的全面评估，包括病毒滴度 血清，肝脏和外周血单核细胞（PBMC）和基线 准蛋白酶的复杂性将获得。酒精摄入的受试者 > 30克/天（女性）或> 60 gm/天（男性）将被建议完全 弃权。 150名受试者的子集饮酒<15 gm/天（女性）或<30 gm/天 （雄性）酒精将被随机戒酒或不变酒精变化 进气（对照组）。我们每年都会再读酒精问卷 （12个月的数量/频率问卷，国家酒精调查）和 对铁蛋白，转氟蛋白饱和和血清氨基转移酶进行测试 活动。 HCV病毒准确性变异性（通过杂化评估 迁移率分析）HCV RNA定量和细胞因子曲线将进行比较 不同的组织来源（血清，PBMC和肝脏）。肝活检将 在基线并在4年后随访中获得以评估严重性 和肝病的进展。这项研究将确定1）数量 与HCV肝脏进展有关的酒精摄入模式 疾病; 2）“中等”或“光”中的酒精是否禁欲 饮酒者降低了HCV疾病进展的速度； 3）主人 （包括促炎或纤维化宿主基因 酒精的存在）和病毒因素（包括准菜 可能会因饮酒而改变的异质性） 使用酒精的HCV感染患者的疾病进展率提高。