Comparative cost-effectiveness of HCC prevention in metabolic dysfunction associated fatty liver disease

肝细胞癌是美国人癌症死亡增长最快的原因。新陈代谢 (功能障碍)相关性脂肪肝(MAFLD)现在是慢性肝病的主要原因，并将 成为肝细胞癌的首要危险因素。肝细胞癌患者多为晚期，生存率低。 因此，需要对肝癌进行预防，以减轻MAFLD肝癌的负担。周围有几个缝隙 MAFLD肝癌的预防。实践指南推荐基于超声的肝细胞癌监测，因为它可以 通过在可治疗的情况下检测癌症来降低肝硬化患者中与肝癌相关的发病率和死亡率 舞台。然而，这一临床证据和相应的指南是基于以下研究的过时数据： 患有丙型或乙肝的患者，不能推断为患有MAFLD的患者，因为患MAFLD的风险较低 肝细胞癌和更高的心血管死亡率。二甲双胍和他汀类药物联合应用预防肝癌 丰厚的承诺。然而，关于肝癌监测的长期危害和益处的证据有限。 或对患有MAFLD的个体进行化学预防。理想情况下，大型随机对照试验(RCT)应该解决 这些数据缺口。然而，由于可行性和伦理方面的考虑，这些试验很难进行。 项目3的目标是通过评估比较成本效益来降低与肝癌相关的死亡率和负担 对MAFLD患者的预防策略进行评估。将来自多个已发布来源的信息与 来自约4000名MAFLD肝硬变患者的前瞻性多部位队列的新原始数据(项目1 计划项目)，以及在580,000名不同地域的大型回溯性队列中进行的模拟RCT MAFLD患者(计划项目的项目2)，我们将开发决策分析模型， 权衡肝细胞癌监测和/或化学预防在MAFLD个体中的风险(成本)和收益。 在目标1中，我们将使用创新的决策分析方法，模拟MAFLD的自然历史和 将文献中的关键数据和两个独特的两个队列合并到本计划项目中。我们将使用 该模型模拟虚拟试验，比较无肝细胞癌监测的长期益处、危害和成本 监测，以及利用超声波和 还有新的成像和血清生物标记物。在具体目标2中，我们将扩展模型以确定何时和 对于哪些亚组的MAFLD患者来说，化学预防的益处大于危害，以及何时开始 停止化学预防。为了确保我们的结果对MAFLD患者和他们的临床医生有用， 我们将开发一个交互式的决策支持工具，HCC模拟器，它将提供个性化的长期 结果，在有和没有肝癌监测和/或化学预防的情况下(具体目标3)。肝细胞癌模拟器 还将作为其他用户进行虚拟试验的平台，以评估Novity的风险(成本)和收益 监控模式。通过提供第一个全面的证据来证明 以肝癌预防为目标，我们的项目将对MAFLD的肝癌预防指南产生强大的影响。

Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer deaths among Americans. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is now the leading cause of chronic liver disease and will become the leading risk factor for HCC. Most HCC patients present with advanced stage and have low survival. Therefore, HCC prevention is required to reduce the burden of MAFLD HCC. There are several gaps around prevention of MAFLD HCC. Practice guidelines recommend ultrasound-based HCC surveillance because it can reduce HCC-related morbidity and mortality among individuals with cirrhosis by detecting cancer at a treatable stage. However, this clinical evidence and corresponding guidelines are based on outdated data from studies of patients with hepatitis C or B and cannot be extrapolated to individuals with MAFLD because of a lower risk of HCC and a higher competing cardiovascular mortality. HCC chemoprevention with metformin and statins hold substantial promise. However, limited evidence exists on the long-term harms and benefits of HCC surveillance or chemoprevention in individuals with MAFLD. Ideally, large randomized controlled trials (RCTs) should address these data gaps. However, these trials are difficult to conduct due to feasibility and ethical concerns. The goal of Project 3 is to reduce HCC related mortality and burden by evaluating comparative cost-effectiveness of prevention strategies in individuals with MAFLD. Combining information from several published sources with new original data from a prospective multi-site cohort of ~4000 patients with MAFLD cirrhosis (Project 1 of the Program Project), and an emulated RCT in a large, geographically diverse retrospective cohort of >580,000 patients with MAFLD (Project 2 of the Program Project), we will develop decision-analytic models that will weigh the risks (costs) and benefits of HCC surveillance and/or chemoprevention in MAFLD individuals. In Aim 1, using innovative decision-analytic approach, we will simulate the natural history of MAFLD and incorporate key data from literature and two unique two cohorts leveraged for this Program Project. We will use this model to simulate a virtual trial comparing long-term benefits, harms, and costs of no HCC surveillance, fixed surveillance, and tailored surveillance (frequency, start/stop times based on risk factors) with ultrasound and also new imaging and serum biomarkers. In Specific Aim 2, we will extend the model to determine when and for which subgroups of MAFLD patients the benefits of chemoprevention outweigh the harms, and when to start and stop chemoprevention. To ensure that our results are useful for patients with MAFLD and their clinicians, we will develop an interactive decision support tool, HCC Simulator, that will provide a personalized long-term outcomes, with and without HCC surveillance and/or chemoprevention (Specific Aim 3). The HCC Simulator will also serve as a platform to other users for conducting virtual trials on risks (costs) and benefits of novel surveillance modalities. By providing the first comprehensive evidence on the comparative cost-effectiveness of targeted HCC prevention, our project will have a powerful impact on guidelines on HCC prevention in MAFLD.