ANTIVIRAL & ANTIFIBROTIC LIVER THERAPY OF HCV+ DRINKERS

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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.