ANTIVIRAL & ANTIFIBROTIC LIVER THERAPY OF HCV+ DRINKERS

抗病毒物质

• 批准号: 6211435
• 负责人: CHARLES S LIEBER
• 金额: $ 50.5万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6211435
• 关键词: alcoholic beverage consumption; chemoprevention; clinical research; combination chemotherapy; fibrogenesis; fibrosis; hepatitis C; hepatitis C virus; human subject; human therapy evaluation; immunotherapy; interferons; liver cirrhosis; liver disorder chemotherapy; phosphatidylcholines; plant extracts; polyenes; ribavirin; soybeans; urinalysis

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.

我们计划评估迄今为止肝炎患者肝炎患者的肝病进展中，抗病毒，抗纤维化和抗氧化剂的联合治疗，即饮酒者。 戒酒者或酒精消费者将进行24-48周的状态抗病毒治疗（Pegypated Intferon + Ibavirin）。 该提案的另一个创新方面是用抗纤维化剂，即从大豆或安慰剂中提取的抗纤维化剂，即聚苯基磷脂酰胆碱（PPC）3年（与抗病毒治疗及其后来同时使用）。 当前的治疗忽略了这样的事实，即导致主要医学症状的原因，最终导致患者的衰老是肝纤维化，导致肝硬化和相关并发症，包括肝细胞癌。如果可以停止甚至阻止纤维化过程，则丙型肝炎病毒将失去其对健康的很大影响。可用的抗纤维化剂过于毒性，无法在患者中使用，除了PPC外，在各种实验模型中已显示出具有引人注目的抗纤维化作用，并且最近发现，在其循环水平的跨激酶水平方面，该患者在HCV+患者中有益。未评估纤维化，但在此提出了PPC对HCV+患者纤维化影响的影响。 值得注意的是，发现PPC也具有显着的抗氧化剂作用。 这在HCV+患者中可能很重要，因为现在各种研究表明HCV与氧化应激有关。 另一个创新的方面是，迄今为止，饮酒者包括被排除在标准抗病毒治疗之外的饮酒者，这主要是因为担心精神障碍，可靠性和依从性加剧。 但是，后一种异议已被卵酸干扰素的可用性克服了，治疗师每周可以以受控的方式对此进行管理。 对于PPC和Ribavirin，将通过在尿液中测量的核黄素等标记（例如核黄素）来监测合规性。 还将进行二烯酰磷脂酰胆碱的血液水平（DLPC，PPC的主要磷脂酰胆碱物种）。因此，请求支持双盲，随机的安慰剂对照研究，以评估这种新型方法治疗HCV+酒精消费者或戒酒者中肝病的功效。 要求资金进行特殊的实验室测试，学习护士，参加会议，患者监测费用和核心办公室。