Evaluating the impact of genetic ancestry and HIV on cirrhosis progression and response to statin therapy among a diverse multi-ethnic cohort of patients with cirrhosis
评估遗传血统和 HIV 对不同多种族肝硬化患者的肝硬化进展和他汀类药物治疗反应的影响
基本信息
- 批准号:10491885
- 负责人:
- 金额:$ 42.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-22 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdmixtureAfrican AmericanAgeAlcoholic HepatitisAlcoholic Liver DiseasesAnimal ModelBiologicalBlack PopulationsCessation of lifeCirrhosisClinicalClinical TrialsCohort StudiesDataDevelopmentEnrollmentEnzymesEquationEsophageal VarixEthnic OriginEthnic groupEtiologyEuropeanEventExposure toFrequenciesFutureGeneticGenetic VariationGoalsHIVHaplotypesHepaticHepatitis BHepatitis C TherapyHepatitis C virusHispanicHispanic PopulationsHydroxymethylglutaryl-CoA reductaseKnowledgeLipidsLiver diseasesMeasurementMeasuresMedicalModelingNative American AncestryOutcomePatient Self-ReportPatientsPharmacogenomicsPopulationPopulation AnalysisPopulation HeterogeneityPortal HypertensionPrimary carcinoma of the liver cellsProspective StudiesProspective cohort studyRaceRandomized Clinical TrialsRandomized Controlled TrialsRiskSafetySimvastatinSocioeconomic FactorsSpainTherapeuticThrombocytopeniaTimeToxic effectUnderrepresented PopulationsVariantVeterans Health AdministrationViral hepatitisbaseclinical practiceclinically significantcohortcomorbiditydemographicsethnic diversitygenetic variantliver stiffnessmortalitymulti-ethnicnon-alcoholic fatty liver diseasenonalcoholic steatohepatitisparticipant enrollmentpatient subsetspreventracial and ethnicracial diversityrecruitresponsesecondary analysis
项目摘要
Project Summary
Despite advances in the treatment of hepatitis C virus (HCV), the number of liver disease-related deaths has
increased annually since 2009 due to: 1) liver disease from non-alcoholic steatohepatitis (NASH) and alcohol-
induced liver disease; and 2) mortality from hepatocellular carcinoma (HCC). The time course to progress from
compensated to decompensated cirrhosis varies based on many factors, such as race/ethnicity, etiology of
liver disease, and medical co-morbidities. Hispanics have the highest age-adjusted cirrhosis mortality rates yet
are underrepresented in the largest US cirrhosis cohort studies. To disentangle whether disparities for
underrepresented populations are due to biological, cultural, and/or socioeconomic factors requires a
prospective study in a racially and ethnically diverse population. Given that genetic variants may be associated
with cirrhosis-related complications and the frequency of these variants likely differ across populations,
analyses cannot simply focus on self-reported race/ethnicity, but rather must incorporate genetic ancestry
information due to the variable genetic admixture of the US population. Another population that has been
shown to have increased risk of hepatic decompensation, and worse survival are HIV-infected patients.
However, these data have been largely restricted to patients with HIV and viral hepatitis. In addition to
identifying the trajectory of compensated cirrhosis, there is a need to identify therapeutics to slow progression.
There are several lines of evidence to suggest that statins slow cirrhosis progression and/or decrease the risk
of decompensation. There are genetic variants/haplotypes in HMGCR associated with clinical responses to
statins that are more prevalent in certain racial/ethnic groups. How these genetic variants might impact the
response to statin therapy among patients with cirrhosis is unknown, and data from other populations may not
apply due to the diversity of the US population. This underscores the need to establish the safety and efficacy
of statins to prevent hepatic decompensation in a US population, and to assess if there are variable responses
to statin therapy that depend in part on underlying genetic variation. Our overarching goal is to develop a
longitudinal prospective cohort study of patients with compensated cirrhosis to assess trajectories of hepatic
stiffness and time to hepatic decompensation. We will enroll a subset with clinically significant portal
hypertension in a randomized controlled trial of simvastatin. By targeting a racially and ethnically diverse cohort
of patients with cirrhosis, with targeted enrollment of patients with HIV, we seek to address these aims to: 1)
determine whether changes in hepatic stiffness and time to hepatic decompensation or death differ based on
genetic ancestry and HIV status in a diverse cohort of patients with cirrhosis; 2) determine whether simvastatin
decreases the risk of hepatic decompensation or death in patients with compensated cirrhosis and clinically
significant portal hypertension (CSPH); and 3) assess whether there are interactions between a) genetic
ancestry or b) HIV status and response to simvastatin.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
David Seth Goldberg其他文献
Multivisceral transplantation utilizing hepatitis C virus–viremic donors for hepatitis C virus–negative recipients
利用丙型肝炎病毒阳性供体为丙型肝炎病毒阴性受者进行多器官联合移植
- DOI:
10.1016/j.ajt.2024.09.006 - 发表时间:
2025-01-01 - 期刊:
- 影响因子:8.200
- 作者:
Vanessa Addison;David Seth Goldberg;Rodrigo Vianna;Eric Martin;Jenn Garcia - 通讯作者:
Jenn Garcia
David Seth Goldberg的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('David Seth Goldberg', 18)}}的其他基金
3/4-The INTEGRATE Study: Evaluating INTEGRATEd Care to Improve Biopsychosocial Outcomes of Early Liver Transplantation for Alcohol-Associated Liver Disease
3/4-综合研究:评估综合护理以改善酒精相关性肝病早期肝移植的生物心理社会结果
- 批准号:
10710924 - 财政年份:2023
- 资助金额:
$ 42.54万 - 项目类别:
A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)
将丙型肝炎病毒血症肾脏移植到丙型肝炎阴性肾脏接受者的试验(THINKER-NEXT)
- 批准号:
10605313 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
Evaluating the impact of genetic ancestry and HIV on cirrhosis progression and response to statin therapy among a diverse multi-ethnic cohort of patients with cirrhosis
评估遗传血统和 HIV 对不同多种族肝硬化患者的肝硬化进展和他汀类药物治疗反应的影响
- 批准号:
10700141 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
Evaluating the impact of genetic ancestry and HIV on cirrhosis progression and response to statin therapy among a diverse multi-ethnic cohort of patients with cirrhosis
评估遗传血统和 HIV 对不同多种族肝硬化患者的肝硬化进展和他汀类药物治疗反应的影响
- 批准号:
10310739 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)
将丙型肝炎病毒血症肾脏移植到丙型肝炎阴性肾脏接受者的试验(THINKER-NEXT)
- 批准号:
10095988 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
A trial of transplanting Hepatitis C-viremic kidneys into Hepatitis C-Negative kidney recipients (THINKER-NEXT)
将丙型肝炎病毒血症肾脏移植到丙型肝炎阴性肾脏接受者的试验(THINKER-NEXT)
- 批准号:
10392517 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
Developing High-Quality Tools to Characterize Allograft Quality, Predict Transplant Outcomes and Expand Access to Kidney and Liver Transplantation
开发高质量工具来表征同种异体移植质量、预测移植结果并扩大肾移植和肝移植的机会
- 批准号:
10201592 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Developing High-Quality Tools to Characterize Allograft Quality, Predict Transplant Outcomes and Expand Access to Kidney and Liver Transplantation
开发高质量工具来表征同种异体移植质量、预测移植结果并扩大肾移植和肝移植的机会
- 批准号:
10605254 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Developing High-Quality Tools to Characterize Allograft Quality, Predict Transplant Outcomes and Expand Access to Kidney and Liver Transplantation
开发高质量工具来表征同种异体移植质量、预测移植结果并扩大肾移植和肝移植的机会
- 批准号:
10413907 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Using ethics, epidemiology and high-quality data to optimize the allocation of livers for transplantation
利用伦理学、流行病学和高质量数据来优化移植肝脏的分配
- 批准号:
10356830 - 财政年份:2019
- 资助金额:
$ 42.54万 - 项目类别:
相似海外基金
Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study
非裔美国儿童急性淋巴细胞白血病的混合分析:ADMIRAL 研究
- 批准号:
10307680 - 财政年份:2021
- 资助金额:
$ 42.54万 - 项目类别:
Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study
非裔美国儿童急性淋巴细胞白血病的混合分析:ADMIRAL 研究
- 批准号:
10902170 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study
非裔美国儿童急性淋巴细胞白血病的混合分析:ADMIRAL 研究
- 批准号:
10626271 - 财政年份:2020
- 资助金额:
$ 42.54万 - 项目类别:
Admixture mapping in African American Asthmatic Children
非洲裔美国哮喘儿童的混合图谱
- 批准号:
8669058 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
Admixture mapping in African American Asthmatic Children
非洲裔美国哮喘儿童的混合图谱
- 批准号:
7922462 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
Admixture mapping in African American Asthmatic Children
非洲裔美国哮喘儿童的混合图谱
- 批准号:
8111129 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
Admixture mapping in African American Asthmatic Children
非洲裔美国哮喘儿童的混合图谱
- 批准号:
8272573 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
Admixture mapping in African American Asthmatic Children
非洲裔美国哮喘儿童的混合图谱
- 批准号:
8471167 - 财政年份:2010
- 资助金额:
$ 42.54万 - 项目类别:
Admixture Mapping of Sarcoidosis Genes in African American
非洲裔美国人结节病基因的混合图谱
- 批准号:
8079699 - 财政年份:2008
- 资助金额:
$ 42.54万 - 项目类别:
Genetic Admixture Study of Uterine Fibroids in African American Women
非裔美国女性子宫肌瘤的基因混合研究
- 批准号:
7750614 - 财政年份:2008
- 资助金额:
$ 42.54万 - 项目类别: