Antiviral/Antifibrotic Liver Therapy of HCV+ Drinkers

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DESCRIPTION (provided by applicant): We plan to continue our study of liver disease treatment in HCV+ patients who abstain from alcohol or drink lightly (1-13 drinks per month) or moderately (4-14 drinks per week). Our start was delayed because of the need to replace some of the initially recruited centers, as well as slow IRB approval and enlistment of personnel. Recruitment is now on track and we request a 2-year extension of the study to achieve its goals. We will continue to treat HCV+ alcohol consumers or abstainers with state-of-the-art antiviral treatment (pegylated interferon + ribavirin) for 24-48 weeks (depending on the genotype), supplemented with placebo or polyenylphosphatidylcholine (PPC), an innocuous antifibrotic and antioxidant agent extracted from soybeans, administered for 3 years, starting with the antiviral treatment. We have enrolled 207 patients and completion of the treatment would be accomplished within the 2 year extension. Thus far, adverse events and dropout rates have not exceeded the anticipated levels. With regard to the primary outcome measure, namely hepatic fibrosis, a preliminary analysis in our first 38 patients who completed their 36 months of treatment revealed that those given PPC had significantly less fibrosis than those taking placebo (p=0.0119). Concerning secondary outcome measures, PPC resulted in a significant decrease of circulating SCOT and SGPT (p=0.0035 and 0.0059 respectively). Furthermore, in the subjects with genotype 1, who are the majority of our patients, the response appeared enhanced when the antiviral treatment was supplemented with PPC. These effects probably result from inhibition, by PPC, of the oxidative stress generated by the virus. This oxidative stress is known to favor the virus' implantation and persistence in the liver. In addition, our preliminary data obtained at 12 and 18 months also showed no consistent effect of moderate drinking on qualitative HCV RNA; Preliminary data also revealed an excellent correlation of liver fibrosis with the serum markers PIIINP, TIMP-1 and collagen IV at baseline and after 36 months of treatment (p=0.003, 0.038 and 0.006, respectively). We will be able to expand all these and other results with the requested extension. Thus far, overall compliance was satisfactory. Accordingly, the Data and Safety Monitoring Board approved this request for continuation of the study to allow its completion. If our encouraging preliminary results are confirmed, we will be able to attenuate the injurious effects engendered by hepatitis C with the inclusion of PPC in the treatment and, consequently, the disease would loose much of its impact on health. Accordingly, support is requested for the completion of this novel approach for the treatment of HCV+ patients who become abstinent or who continue to consume alcohol moderately.