Lifetime Drinking Patterns & HCV Treatment Outcomes

描述（由申请人提供）：这是一项在接受抗病毒治疗的HCV+患者中进行的终生酒精和药物使用研究。它将提供所需的数据，为制定循证指南提供信息，用于治疗有既往或当前酒精和/或药物使用史的HCV+患者。缺乏对HCV患者酒精和药物使用的研究，因为最近或目前的药物滥用是抗病毒治疗的禁忌症，并且尚未在轻度，中度饮酒者中进行系统研究。在饮酒者和吸毒者中建立治疗HCV的有效指南的临床和公共卫生重要性记录在以下报告中：HCV+患者中普遍存在药物使用和重度饮酒史，即使是适度饮酒也可能增加HCV患者的肝病进展，酒精和药物使用可能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，饮酒会削弱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凯萨永久医疗中心对500例接受聚乙二醇干扰素和利巴韦林治疗的HCV阳性患者进行。与患者HCV治疗相关的临床信息将从Kaiser的实验室检查、病理学报告和医疗利用的计算机化数据库中提取，并从记录HCV治疗监测的纸质医疗报告中提取。将对终生物质使用进行详细评估，以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他们是HCV+的时间，2）从患者得知他们是HCV+到开始HCV治疗的时间，3）在HCV治疗期间，和4）在HCV治疗完成后的六个月期间。将采用路径分析技术研究：1）饮酒模式对持续病毒应答（SVR，定义为治疗结束后6个月血清中无HCV RNA）的直接影响; 2）饮酒模式通过降低抗病毒治疗依从性对SVR的间接影响; 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。Probit和逻辑回归分析将用于研究饮酒模式和SVR之间显著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消费以优化SVR率以及持续多长时间;如果HCV治疗结束后再次开始饮酒，治疗结束病毒应答的患者是否无法获得SVR，以及抗病毒治疗是否会促使前物质滥用者复发？

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?).