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）是美国增长最快的癌症死亡原因。代谢