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

代谢功能障碍相关脂肪肝疾病中 HCC 预防的比较成本效益

• 批准号: 10410752
• 负责人: Jagpreet Chhatwal
• 金额: $ 20.19万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410752
• 关键词: Address; Adult; Advisory Committees; Affect; Alcoholic Liver Diseases; American; Biological Markers; Cancer Etiology; Cardiovascular system; Cessation of life; Chemoprevention; Cirrhosis; Clinical; Complement; Costs and Benefits; Data; Diabetes Mellitus; Ensure; Ethics; Etiology; Frequencies; Geography; Goals; Guidelines; Hepatitis B; Hepatitis C; Heterogeneity; Image; Individual; Life; Life Expectancy; Literature; Malignant Neoplasms; Metabolic; Metabolic dysfunction; Metabolic syndrome; Metformin; Modality; Modeling; Morbidity - disease rate; Natural History; Obesity; Outcome; Patients; Physicians; Policies; Practice Guidelines; Prevention; Prevention strategy; Preventive service; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Provider; Publishing; Randomized Controlled Trials; Recommendation; Reporting; Research; Retrospective cohort; Risk; Risk Factors; Screening for cancer; Sensitivity and Specificity; Serum; Severities; Site; Source; Subgroup; Testing; Time; United States; Work; base; chronic liver disease; clinical care; cohort; comparative; comparative cost effectiveness; comparative effectiveness; cost; cost effective; cost effectiveness; fatty liver disease; high risk; individual patient; innovation; lifetime risk; mathematical model; metabolic-associated fatty liver disease; mortality; novel; novel marker; personalized approach; prevent; programs; prospective; screening; screening guidelines; simulation; support tools; surveillance strategy; tool; trait; trial comparing; ultrasound; virtual

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.

肝细胞癌（HCC）是美国人中增长最快的癌症死亡原因。代谢 （功能障碍）相关脂肪肝（MAFLD）现在是慢性肝病的主要原因， 成为肝细胞癌的主要危险因素。大多数HCC患者表现为晚期，生存率低。 因此，需要预防HCC以减少MAFLD HCC的负担。周围有几个缺口 预防MAFLD HCC。实践指南推荐基于超声的HCC监测，因为它可以 通过检测可治疗的癌症，降低肝硬化患者的HCC相关发病率和死亡率。 阶段然而，这些临床证据和相应的指南是基于来自以下研究的过时数据： 丙型肝炎或B型肝炎患者，由于MAFLD的风险较低， HCC和更高的竞争性心血管死亡率。二甲双胍和他汀类药物用于肝癌化学预防 实质性承诺。然而，有限的证据存在的长期危害和利益的肝癌监测 或MAFLD患者的化学预防。理想情况下，大型随机对照试验（RCT）应解决 这些数据缺口。然而，由于可行性和伦理问题，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HCC相关死亡率和负担 MAFLD患者的预防策略。将来自多个已发布来源的信息与 来自一项前瞻性多中心队列的新原始数据，该队列约有4000例MAFLD肝硬化患者（项目1）。 计划项目），并在一个大型的，地理分布多样的回顾性队列中进行模拟RCT， MAFLD患者（计划项目2），我们将开发决策分析模型， 在MAFLD个体中权衡HCC监测和/或化学预防的风险（成本）和益处。 在目标1中，使用创新的决策分析方法，我们将模拟MAFLD的自然历史， 结合文献中的关键数据和本计划项目所利用的两个独特的两个队列。我们将使用 该模型模拟了一项虚拟试验，比较了无HCC监测的长期获益、危害和成本， 监测和定制监测（频率，基于风险因素的开始/停止时间）， 还有新的成像和血清生物标志物。在特定目标2中，我们将扩展模型以确定何时以及 对于MAFLD患者的哪些亚组，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患者及其临床医生有用， 我们将开发一个交互式决策支持工具，HCC模拟器，它将提供一个个性化的长期 结果，有和没有HCC监测和/或化学预防（具体目标3）。HCC模拟器 还将作为一个平台，为其他用户进行虚拟试验的风险（成本）和好处的新的 监视模式。通过提供第一个全面的证据， 有针对性的HCC预防，我们的项目将对MAFLD中HCC预防的指南产生强大的影响。