Antiviral/Antifibrotic Liver Therapy of HCV+ Drinkers

HCV 饮酒者的抗病毒/抗纤维化肝治疗

• 批准号: 7046265
• 负责人: CHARLES S LIEBER
• 金额: $ 15.9万
• 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 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046265
• 关键词: alcoholic beverage consumption; antioxidants; antiviral agents; chemoprevention; clinical research; combination chemotherapy; drug /alcohol abstinence; fibrogenesis; fibrosis; genotype; hepatitis C; hepatitis C virus; host organism interaction; human subject; human therapy evaluation; immunotherapy; interferons; liver cirrhosis; liver disorder chemotherapy; liver pharmacology; patient oriented research; pharmacogenetics; phosphatidylcholines; plant extracts; polyenes; ribavirin; soybeans

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.

描述（由申请人提供）：我们计划继续对戒酒或轻轻饮用（每月1-13饮料）或中度（每周4-14饮料）的HCV+患者进行肝病治疗研究。我们的起点被推迟了，因为需要取代一些最初招募的中心，以及慢慢的IRB批准和人员入伍。招聘现在正在正轨，我们要求对研究的2年延长以实现其目标。我们将继续使用最先进的抗病毒药物治疗（Pegypated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），并补充了安慰剂或聚磷脂酰胆碱（PPC），与您的抗抗毒剂和抗毒剂的启动，是一种依从型抗毒剂和抗毒剂，是源自服务的疾病，是源自的疾病，是促进的抗毒剂和抗毒剂。抗病毒治疗。我们已经招募了207名患者，并且将在两年内完成治疗。到目前为止，不利事件 辍学率尚未超过预期的水平。关于主要结局指标，即肝纤维化，在我们的前38名患者中，完成了36个月治疗的患者的初步分析表明，给定的PPC的纤维化明显少于安慰剂（p = 0.0119）。关于次级结果度量，PPC导致循环SCOT和SGPT显着减少（分别为p = 0.0035和0.0059）。此外，在大多数患者的基因型1受试者中，当抗病毒药治疗补充PPC时，反应似乎增强了。这些作用可能是由PPC抑制引起的，对病毒产生的氧化应激。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个月获得的初步数据也显示出适度饮酒对定性HCV RNA的一致作用。初步数据还表明，基线和36个月后的肝纤维化与血清标记，TIMP-1和胶原蛋白IV的良好相关性（分别为p = 0.003、0.038和0.006）。我们将能够通过请求的扩展名扩展所有这些结果和其他结果。到目前为止，总体合规性令人满意。因此，数据和安全监控委员会批准了该请求继续进行研究，以完成其完成。如果确认我们令人鼓舞的初步结果，我们将能够通过将PPC纳入治疗中，从而减轻乙型肝炎产生的伤害作用，因此，该疾病将使其对健康的影响很大。因此，请求支持这种新颖的方法来治疗戒酒或继续中度饮酒的HCV+患者。