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）是美国人癌症死亡增长最快的原因。代谢 （功能障碍）相关脂肪肝病（MAFLD）现在是慢性肝病的主要原因，并将 成为 HCC 的首要危险因素。大多数 HCC 患者已处于晚期且生存率较低。 因此，需要预防HCC以减轻MAFLD HCC的负担。周围有几个缝隙 预防 MAFLD 肝癌。实践指南推荐基于超声的 HCC 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 HCC 相关的发病率和死亡率 阶段。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： 丙型肝炎或乙型肝炎患者，不能外推至患有 MAFLD 的个体，因为其风险较低 HCC 和更高的心血管死亡率。使用二甲双胍和他汀类药物进行 HCC 化学预防有效 实质性的承诺。然而，关于 HCC 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) 应解决 这些数据差距。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。结合多个已发布来源的信息 来自约 4000 名 MAFLD 肝硬化患者的前瞻性多中心队列的新原始数据（项目 1） 计划项目），以及在超过 580,000 名来自不同地域的大型回顾性队列中进行的模拟随机对照试验 MAFLD 患者（该项目的项目 2），我们将开发决策分析模型，该模型将 权衡 MAFLD 个体 HCC 监测和/或化学预防的风险（成本）和益处。 在目标 1 中，我们将使用创新的决策分析方法来模拟 MAFLD 的自然历史并 纳入了文献中的关键数据以及该计划项目所利用的两个独特的两个队列。我们将使用 该模型模拟虚拟试验，比较无 HCC 监测的长期益处、危害和成本，固定 监测和定制监测（频率、基于风险因素的开始/停止时间），包括超声波和 还有新的成像和血清生物标志物。在具体目标 2 中，我们将扩展模型以确定何时和 对于哪些 MAFLD 患者亚组，化学预防的益处大于危害，以及何时开始 并停止化学预防。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 Simulator，它将提供个性化的长期 有或没有 HCC 监测和/或化学预防的结果（具体目标 3）。 HCC 模拟器 还将作为其他用户对新型药物的风险（成本）和收益进行虚拟试验的平台 监视方式。通过提供关于比较成本效益的第一个全面证据 有针对性的 HCC 预防，我们的项目将对 MAFLD 的 HCC 预防指南产生重大影响。