Chemoprevention of HCC related to MAFLD
与 MAFLD 相关的 HCC 的化学预防
基本信息
- 批准号:10410751
- 负责人:
- 金额:$ 21.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAdverse eventAffectAgeAmericanCancer EtiologyCessation of lifeChemopreventionChemopreventive AgentChildCirrhosisClinicalClinical TrialsCohort StudiesComplementDataDiabetes MellitusDoseDyslipidemiasEtiologyEvaluationFibrosisFoundationsGeneral PopulationGenesGeneticGenetic DeterminismGenetic MarkersGoalsGuidelinesHepatocarcinogenesisHeterogeneityHigh PrevalenceHospitalsHybridsIndividualKnowledgeLaboratoriesLinkLipidsLiverLiver CirrhosisLiver diseasesMachine LearningMalignant neoplasm of liverManualsMeasuresMedicalMetabolicMetabolic DiseasesMetabolic dysfunctionMetabolic syndromeMetforminNatural Language ProcessingNon obeseObesityOutcomePathogenesisPathway interactionsPatientsPersonsPharmaceutical PreparationsPharmacoepidemiologyPharmacologyPharmacy facilityPhenotypePioglitazonePopulationPreventionPrimary carcinoma of the liver cellsProspective cohortRegistriesReportingResearchResearch DesignRetrospective cohortRiskRisk FactorsSeriesSeveritiesSeverity of illnessSubgroupThiazolidinedionesToxic effectUnited States Department of Veterans AffairsWorkadverse event riskbasebiological adaptation to stressburden of illnesscancer chemopreventioncancer riskcarcinogenesischronic liver diseaseclinical practicecohortcomparativecurative treatmentsdesigndiabetes controlexperimental studyfatty liver diseasehigh riskhigh risk populationinnovationmetabolic-associated fatty liver diseasemortalityneoplasm registrynovelpredicting responsepreventprogramsresponsestemtraittumor
项目摘要
Metabolic (dysfunction) associated fatty liver disease (MAFLD) is now one of the most important risk factors for
hepatocellular cancer (HCC) in the U.S. Currently, no liver-specific therapies are approved for individuals with
MAFLD. Therapy that may block hepatocarcinogenesis – i.e., chemoprevention – is the only practical solution
to stem the rising tide of MAFLD-related HCC. In this context, three classes of medications (statins, metformin,
and glitazones) hold substantial promise because they act on different metabolic and/or stress-response
pathways important in MAFLD-related hepatocarcinogenesis, are commonly used to treat metabolic disorders,
and widely available. To our knowledge, no study has examined HCC chemoprevention in MAFLD. There is
also limited information about potential harms of these drugs, especially liver related adverse events (AEs)
which may be common in persons with MAFLD. The benefits and harms of chemoprevention are likely different
in different subgroups. Our study will evaluate the benefits and harms of HCC chemoprevention with these
three promising therapies in individuals with MAFLD. To do so, we will use, expand and extend a
previously assembled, well-characterized national cohort of MAFLD patients with extensive longitudinal clinical,
pharmacy, and laboratory data linked to detailed information from cancer registry, death registry and clinician
notes. Using this cohort, and as part of preliminary work, we showed a strong association between MAFLD and
HCC and reported an additive effect of metabolic traits on HCC risk. For Aim 1 (benefits of
chemoprevention), we will perform a series of carefully designed studies to evaluate the chemopreventive
effects of statins (vs. no statins), metformin (vs. no metformin) and pioglitazone (vs. no pioglitazone) in
reducing risk of incident HCC. We will also assess the heterogeneity of chemopreventive effects, with specific
focus on MAFLD patients with and without cirrhosis, those with varying severity of co-existing metabolic traits,
and perform dose-duration analyses to guide tailored chemoprevention. For Aim 2 (harms of
chemoprevention), we will use innovations in machine learning followed by manual review of medical charts
to conduct a comprehensive comparative evaluation of potential drug-related AEs among patients included in
Aim 1 emulated trials. Studies show that genetic factors contribute to differences in response to cancer
chemoprevention. In Aim 3 (genetic determinants of benefits), we will use data from an ongoing prospective
cohort of patients with MAFLD-cirrhosis to examine few suspected genetic markers that may modify the
chemopreventive effects of metformin and/or statins in individuals with MAFLD-cirrhosis. Our research is
significant because it will inform guidelines about who, when and how to recommend chemoprevention in
patients with MAFLD. Besides elucidating a potential chemopreventive effect in the general MAFLD population,
our emphasis on personalized chemoprevention is novel.
代谢性(功能障碍)相关脂肪肝(MAFLD)是目前最重要的危险因素之一
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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FASIHA KANWAL的其他文献
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{{ truncateString('FASIHA KANWAL', 18)}}的其他基金
Chemoprevention of HCC related to MAFLD
与 MAFLD 相关的 HCC 的化学预防
- 批准号:
10657423 - 财政年份:2022
- 资助金额:
$ 21.22万 - 项目类别:
Clinical Validation Center for Hepatocellular Carcinoma
肝细胞癌临床验证中心
- 批准号:
10676320 - 财政年份:2022
- 资助金额:
$ 21.22万 - 项目类别:
Multi-level Evaluation of Racial/ethnic Disparities in Liver Disease Outcomes
肝病结果中种族/民族差异的多层次评估
- 批准号:
10374004 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别:
Multi-level Evaluation of Racial/ethnic Disparities in Liver Disease Outcomes
肝病结果中种族/民族差异的多层次评估
- 批准号:
10606494 - 财政年份:2021
- 资助金额:
$ 21.22万 - 项目类别:
Patient centered care for individuals with advanced liver disease
以患者为中心的晚期肝病患者护理
- 批准号:
9701020 - 财政年份:2018
- 资助金额:
$ 21.22万 - 项目类别:
Risk Stratification for and Early Detection of Liver Cancer
肝癌的风险分层和早期发现
- 批准号:
10473708 - 财政年份:2018
- 资助金额:
$ 21.22万 - 项目类别:
Patient centered care for individuals with advanced liver disease
以患者为中心的晚期肝病患者护理
- 批准号:
10186511 - 财政年份:2018
- 资助金额:
$ 21.22万 - 项目类别:
Risk Stratification for and Early Detection of Liver Cancer
肝癌的风险分层和早期发现
- 批准号:
10239079 - 财政年份:2018
- 资助金额:
$ 21.22万 - 项目类别:
Care for Women Veterans with Hepatitis C Virus Infection
照顾感染丙型肝炎病毒的女性退伍军人
- 批准号:
8596038 - 财政年份:2014
- 资助金额:
$ 21.22万 - 项目类别:
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