Addressing Hepatitis C and Hepatocellular Carcinoma: Current and Future Epidemics

描述（由申请人提供）：在美国，丙型肝炎病毒（HCV）相关死亡人数现已超过HIV相关死亡人数。在世界各地，HCV在注射毒品者（PWID）中高流行。急性HCV感染的新爆发正在与男性发生性关系的艾滋病毒阳性男性（MSM）和从滥用处方阿片类药物过渡到非法阿片类药物注射的15-24奥尔兹中展开。在慢性丙型肝炎病毒感染患者中，20-25%的人会患上肝脏疾病，可能表现为肝硬化、肝衰竭或肝细胞癌（HCC）。肝细胞癌的预后极差，HCV是这类癌症的主要病原体。HCV预防和治疗方面的最新发现为逆转HCV、HCV/HIV合并感染和HCC发病率增加的趋势提供了很好的机会。本研究将使用实施科学的方法-研究综合，数学建模和模拟，以及比较有效性分析-以确定如何最好地构成一个组合的干预措施，以预防和控制丙型肝炎及其后果，同时考虑到有限的资源和潜在的流行病学和社会网络功能的帐户。传播计划将广泛利用技术，包括社交媒体和主要利益攸关方的指导。这些是我们的具体目标：1。综合表征以下特征的证据：a）从处方阿片类药物滥用到药物注射的过渡，B）PWID和HIV+ MSM的HCV流行病学和预防，以及c）这两个组中HCV疾病的进展和治疗，以得出最佳估计值，以填充我们的HCV自然史和传播模型。2.使用基于代理的建模来评估扩大单独和联合预防和治疗相关干预措施对PWID和HIV+MSM中HCV传播和自然史的影响。3.确定特定预算和流行病学情景的干预组合，a）最大限度地减少急性和慢性HCV感染，包括HIV/HCV合并感染，B）预防最大数量的HCV相关HCC病例和其他严重后遗症，c）最大限度地延长预期寿命和质量调整预期寿命，d）减少健康差距。4.与我们的传播咨询委员会合作，采用综合知识交流方法，为我们的目标受众（政策制定者，公共卫生和减少危害实践社区，PWID和HIV+MSM）提供知识和工具，以实施循证HCV控制策略或减少个人感染风险及其后果。这项研究的主要目的是提供一个证据基础，以指导分配稀缺的公共资源，在美国和其他国家，丙型肝炎病毒主要是传播PWID。这将通过综合、建模和将HCV流行病学、预防和治疗的最新发展转化为实用工具来实现，以优化人群健康。

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV)-related deaths now exceed HIV-related deaths in the US. Throughout the world, HCV is hyperendemic in people who inject drugs (PWID). New outbreaks of acute HCV infection are unfolding in HIV-positive men who have sex with men (MSM) and in 15-24 year olds who have transitioned from abuse of prescription opioids to illicit opiate injection. In patients with chronic HCV infection, 20-25% wil develop liver disease which may manifest as cirrhosis, liver failure or hepatocellular carcinoma (HCC). The prognosis for HCC is extremely poor, and HCV is the chief etiologic agent for this type of cancer. Recent discoveries in HCV prevention and treatment provide a great opportunity to reverse the trend toward increasing rates of HCV, HCV/HIV co-infection, and HCC. This study will use the methods of Implementation Science - research synthesis, mathematical modeling and simulation, and comparative effectiveness analyses - to determine how best to constitute a portfolio of interventions for the prevention and control of HCV and its consequences while taking into limited resources and underlying epidemiologic and social network features account. A dissemination plan will make extensive use of technology, including social media, and guidance from key stakeholders. These are our specific aims: 1. Synthesize evidence characterizing a) transition from misuse of prescription opioids to drug injection, b) HCV epidemiology and prevention for PWID and HIV+ MSM, and c) progression and treatment of HCV disease in these two groups, to derive best estimates to populate our HCV natural history and transmission models. 2. Use agent-based modeling to estimate the effects of scale-up of individual and combined prevention- and treatment-related interventions on HCV transmission and natural history in PWID and HIV+MSM. 3. Determine the combination of interventions for particular budget and epidemiologic scenarios that a) minimizes acute and chronic HCV infections, including HIV/HCV co-infection, b) prevents the greatest number of cases of HCV-related HCC and other serious sequelae, c) maximizes life expectancy and quality- adjusted life expectancy and d) reduces health disparities. 4. In collaboration with our Dissemination Advisory Board, apply an integrated knowledge-exchange approach to providing our target audiences (policymakers, public health and harm reduction practice communities, PWID and HIV+MSM) with the knowledge and tools to implement evidence-based HCV control strategies or reduce personal risk of infection and its consequences. The broad objective of this study is to provide an evidence base to guide allocation of scarce public resources in the US and other countries where HCV is principally transmitted among PWID. This will be accomplished by synthesizing, modeling and translating very recent developments in HCV epidemiology, prevention and treatment into practical tools to optimize population health.