ANTIVIRAL & ANTIFIBROTIC LIVER THERAPY OF HCV+ DRINKERS

我们计划评估一种联合抗病毒、抗纤维化和抗氧化治疗在迄今排除的丙型肝炎患者即饮酒者肝病进展中的作用。戒酒者或饮酒者将接受最先进的抗病毒治疗(聚乙二醇化干扰素利巴韦林)，为期24-48周。这项建议的另一个创新方面是补充了一种抗纤维化药物，即从大豆中提取的多烯基磷脂酰胆碱(PPC)，或安慰剂，为期3年(与抗病毒治疗同时进行，此后)。目前的治疗忽略了这样一个事实，即导致主要医学症状并最终导致患者死亡的是肝纤维化，导致肝硬化和相关并发症，包括肝细胞癌。如果纤维化过程能够被阻止甚至阻止，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，不能用于患者，除了一种名为PPC的药物，它在各种实验模型中被证明具有显著的抗纤维化作用，最近发现它对丙型肝炎患者的循环转氨酶水平是有益的。未对肝纤维化进行评估，但PPC对丙型肝炎患者肝纤维化的影响的文献在这里被提出。值得注意的是，PPC也被发现具有显著的抗氧化作用。这对丙型肝炎患者可能很重要，因为现在各种研究表明，丙型肝炎病毒与氧化应激有关。另一个创新方面是将迄今被排除在标准抗病毒治疗之外的饮酒者包括在内，主要是因为担心精神障碍的恶化、可靠性和遵从性。然而，后者现在已经被聚乙二醇化干扰素的可用性所克服，这种干扰素可以由治疗师以受控的方式每周给药一次。对于PPC和利巴韦林，将通过纳入可以在尿液中测量的核黄素等标记物来监测遵从性。还将抽查血液中的二甘油酰磷脂酰胆碱(DLPC，PPC的主要磷脂酰胆碱种类)的水平。因此，要求支持一项双盲、随机的安慰剂对照研究，以评估这种新方法治疗丙型肝炎病毒饮酒者或戒酒者的肝病的有效性。请拨经费用于特殊实验室测试、研究护士、参加会议的旅费、病人监测费用和一个核心办公室。

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.