Addressing Hepatitis C and Hepatocellular Carcinoma: Current and Future Epidemics

描述(申请人提供)：在美国，丙型肝炎病毒(丙型肝炎病毒)相关死亡人数现已超过艾滋病毒相关死亡人数。在世界各地，丙型肝炎病毒在注射毒品者(PWID)中高度流行。艾滋病毒阳性男男性行为者(MSM)和15-24岁从滥用处方阿片类药物过渡到非法注射阿片类药物的艾滋病毒阳性男性正在爆发新的急性丙型肝炎病毒感染。在慢性丙型肝炎患者中，20-25%的人会发展成肝病，表现为肝硬变、肝功能衰竭或肝细胞癌。肝细胞癌的预后极差，丙型肝炎病毒是该类型癌症的主要病原体。最近在丙型肝炎病毒预防和治疗方面的发现为扭转丙型肝炎病毒、丙型肝炎病毒/艾滋病毒混合感染和肝癌发病率上升的趋势提供了一个很好的机会。这项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效果分析--确定如何在考虑到有限的资源和潜在的流行病学和社会网络特征的情况下，最好地构成预防和控制丙型肝炎及其后果的干预措施组合。传播计划将广泛利用技术，包括社交媒体，以及关键利益攸关方的指导。这些是我们的具体目标：1.综合证据，描述a)从滥用处方阿片类药物到注射药物的转变，b)PWID和HIV+MSM的丙型肝炎流行病学和预防，以及c)这两组丙型肝炎的进展和治疗，以得出最好的估计，以填充我们的丙型肝炎自然历史和传播模型。2.使用基于代理的模型来估计单独和联合预防和治疗相关干预措施的扩大对PWID和HIV+MSM患者的丙型肝炎传播和自然病史的影响。3.确定针对特定预算和流行病学情况的干预措施组合：a)最大限度地减少急性和慢性丙型肝炎感染，包括艾滋病毒/丙型肝炎合并感染；b)预防最大数量的丙型肝炎相关的肝细胞癌和其他严重后遗症；c)最大限度地延长预期寿命和经质量调整的预期寿命；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，向我们的目标受众(政策制定者、公共卫生和减少危害实践社区、PWID和艾滋病毒+男男性接触者)提供知识和工具，以实施循证的丙型肝炎控制战略或减少个人感染风险及其后果。这项研究的广泛目标是提供一个证据基础，以指导在美国和其他丙型肝炎病毒主要在PWID中传播的国家分配稀缺的公共资源。这将通过将丙型肝炎病毒流行病学、预防和治疗方面的最新发展综合、建模并转化为优化人口健康的实用工具来实现。

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.