Antiviral/Antifibrotic Liver Therapy of HCV+ Drinkers

描述（由申请人提供）： 我们计划继续在戒酒或轻度饮酒（每月1-13杯）或中度饮酒（每周4-14杯）的HCV+患者中进行肝病治疗的研究。我们的启动被推迟，因为需要更换一些最初招募的中心，以及缓慢的IRB批准和招募人员。招募工作正在进行中，我们要求将研究延长2年，以实现其目标。我们将继续用最先进的抗病毒治疗（聚乙二醇干扰素+利巴韦林）治疗HCV+酒精消费者或戒酒者24-48周（取决于基因型），并补充安慰剂或多烯磷脂酰胆碱（PPC），一种从大豆中提取的无毒抗纤维化和抗氧化剂，从抗病毒治疗开始给药3年。我们已入组207例患者，将在2年延长期内完成治疗。到目前为止，不良事件 辍学率没有超过预期水平。关于主要结局指标，即肝纤维化，我们对完成36个月治疗的前38例患者进行的初步分析显示，给予PPC的患者的纤维化明显低于服用安慰剂的患者（p=0.0119）。关于次要结局指标，PPC导致循环SCOT和SGPT显著降低（分别为p=0.0035和0.0059）。此外，在基因型1的受试者中，占我们患者的大多数，当抗病毒治疗补充PPC时，反应似乎增强。这些作用可能是PPC抑制病毒产生的氧化应激所致。已知这种氧化应激有利于病毒在肝脏中的植入和持久性。此外，我们在12个月和18个月时获得的初步数据也显示，适度饮酒对定性HCV RNA没有一致的影响;初步数据还显示，在基线和治疗36个月后，肝纤维化与血清标志物PIIINP、TIMP-1和IV型胶原具有良好的相关性（分别为p=0.003、0.038和0.006）。我们将能够扩展所有这些和其他结果与所要求的扩展。到目前为止，总体遵守情况令人满意。因此，数据和安全性监查委员会批准了继续研究的申请，以完成研究。如果我们令人鼓舞的初步结果得到证实，我们将能够通过将PPC纳入治疗中来减轻丙型肝炎所产生的有害影响，因此，这种疾病将失去对健康的大部分影响。因此，需要支持完成这种新的方法，用于治疗戒酒或继续适度饮酒的HCV阳性患者。

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.