Lifetime Drinking Patterns & HCV Treatment Outcomes

描述（由申请人提供）：这是一项针对接受抗病毒治疗的 HCV 患者终生饮酒和吸毒情况的研究。它将提供所需的数据，为制定治疗有过去或现在饮酒和/或吸毒史的 HCV 患者的循证指南提供信息。由于最近或当前的药物滥用是抗病毒治疗的禁忌症，因此缺乏对 HCV 患者饮酒和吸毒的研究，并且尚未对轻度、中度饮酒者进行系统研究。建立有效治疗饮酒者和吸毒者丙型肝炎病毒指南的临床和公共卫生重要性已被以下报告证明：丙型肝炎病毒患者中普遍存在吸毒和酗酒史，即使适量饮酒也可能会增加丙型肝炎患者肝病的进展，酒精和吸毒可能会降低抗病毒治疗方案的依从性，抗病毒治疗可能会引发前吸毒者的复发，饮酒会损害对基于干扰素的抗病毒治疗的反应。研究将在 2002 年或之后在萨克拉门托 Kaiser Permanente 医疗中心以 500 名接受聚乙二醇干扰素和利巴韦林治疗的 HCV 患者为样本进行。与患者 HCV 治疗相关的临床信息将从 Kaiser 的实验室测试、病理报告和医疗护理利用的计算机化数据库以及记录 HCV 治疗监测的纸质医疗报告中提取。将采用对终生物质使用的详细评估来确定药物使用和以下饮酒模式、总消费量、总饮酒频率、每天和每个饮酒日的摄入量以及四个关键时期的不规则饮酒：1) 从开始定期饮酒到患者得知自己患有 HCV 的时间，2) 从患者得知自己患有 HCV 的时间到开始 HCV 治疗的时间，3) 在 HCV 治疗期间，以及 4) 在完成 HCV 治疗后的六个月内。将采用路径分析技术来研究：1）饮酒模式对持续病毒反应（SVR，定义为治疗结束后六个月血清中没有 HCV RNA）的直接影响； 2) 饮酒模式通过减少抗病毒治疗依从性而对 SVR 产生间接影响； 3) 药物使用与 SVR 之间的关系以及药物使用对饮酒模式与依从性之间关系的调节作用。概率和逻辑回归分析将用于调查饮酒模式与 SVR 之间显着关系的临床相关参数（例如，轻度、中度和重度饮酒者需要减少多少酒精摄入量才能优化 SVR 率以及持续多长时间；治疗结束时病毒应答的患者如果在 HCV 治疗结束后再次开始饮酒是否无法获得 SVR？抗病毒治疗是否会导致前药物滥用者复发？）。

DESCRIPTION (provided by applicant): This is a study of lifetime alcohol and drug use among HCV+ patients who have received antiviral therapy. It will provide data needed to inform the development of evidence-based guidelines for treating HCV+ patients with a past or present history of alcohol and/or drug use. Studies of alcohol and drug use in patients with HCV are lacking because recent or current substance abuse is a contraindication for antiviral therapy, and systematic studies have not been conducted in light, moderate drinkers. The clinical and public health importance of establishing effective guidelines for treating HCV in drinkers and drug users is documented by reports that histories of drug use and heavy drinking are prevalent among HCV+ patients, that even moderate drinking may increase the progression of liver disease in HCV patients, that alcohol and drug use may reduce adherence to antiviral treatment regimens, that antiviral treatment may trigger relapses in former drug users, and that drinking impairs responsivity to interferon-based antiviral therapy. Research will be conducted in a sample of 500 HCV+ patients treated with pegylated interferon and ribavirin in the Sacramento Kaiser Permanente Medical Center during or after 2002. Clinical information relevant to patients' HCV treatment will be extracted from Kaiser's computerized databases on laboratory tests, pathology reports, and medical care utilization, and from paper medical reports that document HCV treatment monitoring. Detailed assessments of lifetime substance use will be employed to define drug use and the following alcohol drinking patterns, total consumption, total drinking frequency, intakes per day and per drinking day, and irregular drinking for four critical periods: 1) from the onset of regular drinking to the time patients learned they were HCV+, 2) from the time patients learned they were HCV+ to initiation of HCV treatment, 3) during HCV treatment, and 4) during the six months following completion of HCV treatment. Path analytic techniques will be employed to investigate: 1) direct effects of drinking patterns on sustained viral response (SVR, defined as no HCV RNA in serum six months after treatment ends); 2) indirect effects of drinking patterns on SVR mediated through reduced adherence to antiviral therapy; and 3) relations between drug use and SVR and moderating effects of drug use on the relation between drinking patterns and adherence. Probit and logistic regression analysis will be used to investigate clinically relevant parameters of significant relations between drinking patterns and SVR (e.g., how much do light, moderate, and heavy drinkers need to reduce their alcohol consumption to optimize SVR rates and for how long; do patients with an end-of-treatment viral response fail to obtain an SVR if they start drinking again after HCV treatment ends, and does antiviral treatment precipitate relapses in former substance abusers?).