ANTIVIRAL & ANTIFIBROTIC LIVER THERAPY OF HCV+ DRINKERS

我们计划评估抗病毒、抗纤维化和抗氧化联合治疗对迄今为止排除的丙型肝炎患者（即饮酒者）肝病进展的影响。 戒酒者或饮酒者将接受为期 24-48 周的最先进的抗病毒治疗（聚乙二醇干扰素利巴韦林）。 该提案的另一个创新方面是补充抗纤维化药物，即从大豆中提取的多烯磷脂酰胆碱 (PPC)，或安慰剂，服用 3 年（与抗病毒治疗同时进行）。 目前的治疗忽视了这样一个事实，即导致患者主要医学症状并最终死亡的是肝纤维化，从而导致肝硬化和相关并发症，包括肝细胞癌。如果纤维化过程可以停止甚至预防，丙型肝炎病毒将失去对健康的大部分影响。现有的抗纤维化药物毒性太大，无法用于患者，只有一种药物除外，即 PPC，它已在各种实验模型中显示出显着的抗纤维化作用，并且最近发现它对 HCV 患者的循环转氨酶水平有益。未评估纤维化，但此处提议记录 PPC 对 HCV 患者纤维化的影响。 值得注意的是，PPC 还被发现具有显着的抗氧化作用。 这对于 HCV 患者可能很重要，因为目前各种研究表明 HCV 与氧化应激有关。 另一个创新方面是纳入了迄今为止被排除在标准抗病毒治疗之外的饮酒者，主要是因为担心精神障碍恶化、可靠性和依从性。 然而，后一个反对意见现已被聚乙二醇化干扰素的可用性所克服，聚乙二醇化干扰素可以由治疗师以受控方式每周施用一次。 对于 PPC 和利巴韦林，将通过掺入可在尿液中测量的核黄素等标记物来监测依从性。 还将对二亚油酰磷脂酰胆碱（DLPC，PPC 的主要磷脂酰胆碱种类）的血液水平进行抽查。因此，需要支持一项双盲、随机安慰剂对照研究，以评估这种新方法治疗 HCV 饮酒者或戒酒者肝脏疾病的功效。 需要资金用于特殊实验室测试、研究护士、参加会议的旅行、患者监测费用和核心办公室。

We plan to evaluate a combined antiviral, antifibrotic and antioxidant treatment in the progression of liver disease of heretofore excluded patients with hepatitis C namely alcohol drinkers. Abstainers or alcohol consumers will be given state- of-the-art antiviral treatment (pegylated interferon + ribavirin) for 24-48 weeks. Another innovative aspect of this proposal is the supplemention with an anti-fibrotic agent, namely polyenylphosphatidylcholine (PPC) extracted from soybeans, or placebo, administered for 3 years (concomitantly with the antiviral treatment and thereafter). Current therapy neglects the fact that what causes the major medical symptoms and eventually the demise of the patient is liver fibrosis, resulting cirrhosis and associated complications, including hepatocellular carcinoma. If the fibrotic process could be stopped or even prevented, the hepatitis C virus would lose much of its impact on health. Available anti-fibrotic agents are too toxic to be used in patients, except for one, namely PPC, which has been shown in various experimental models to have striking anti-fibrotic actions, and which was found recently to be beneficial in HCV+ patients in terms of their circulating levels of transaminases. Fibrosis was not assessed, but documentation of the effects of PPC on fibrosis in HCV+ patients is being proposed here. It is noteworthy that PPC was discovered to have also significant anti- oxidant effects. This may be important in HCV+ patients since various studies have now indicated that HCV is associated with an oxidative stress. Another innovative aspect is the inclusion of drinkers who thus far were excluded from standard antiviral treatment, mainly because of concerns about exacerbation of mental disorders, reliability and compliance. However, the latter objection has now been overcome by the availability of pegylated interferon which can be administered once a week by the therapist in a controlled fashion. For both PPC and ribavirin, compliance will be monitored by incorporation of markers, such as riboflavin, that can be measured in the urine. Spot checks of blood levels of dilinoleoylphosphatidylcholine (DLPC, the main phosphatidylcholine species of PPC) will also be performed. Accordingly, support is requested for a a double-blind, randomized placebo controlled study to assess the efficacy of this novel approach for the treatment of liver disease in HCV+ alcohol consumers or abstainers. Funds are requested for special laboratory tests, study nurses, travel to meetings, patient monitoring expenses and a core office.