Impact of Hepatitis C and HIV coinfection on biological aging and hepatocellular carcinoma risk

丙型肝炎和艾滋病毒合并感染对生物衰老和肝细胞癌风险的影响

• 批准号: 10872804
• 负责人: Jose Daniel Debes
• 金额: $ 10万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10872804
• 关键词: 11 year old; Acceleration; Address; Administrative Supplement; Affect; Age; Aging; Biological; Biological Aging; Cancer Etiology; Cessation of life; Chronology; DNA; DNA Modification Process; Development; Epigenetic Process; Evaluation; Fogarty International Center; HIV; HIV Seronegativity; HIV Seropositivity; HIV/HCV; Hepatitis B Infection; Hepatitis B Virus; Hepatitis C; Immune; Individual; Infection; Latin America; Latin American; Longevity; Malignant Neoplasms; Malignant neoplasm of liver; Minnesota; Modification; Patients; Persons; Population; Primary carcinoma of the liver cells; Process; Research; Risk; Training; Universities; Viral; Viral hepatitis; co-infection; high risk; innovation; methylation pattern; parent grant; peripheral blood; programs; response; tool; viral detection

ABSTRACT This application is being submitted in response to a supplement announcement titled: “Catalyzing research and training on the impact of HIV on Aging Across the Lifespan of Persons Living with HIV” through administrative supplements to existing Fogarty International Center HIV programs (HIV-Aging2023S). The applicant’s parent grant (R21TW012390) is titled, Immune profiling to detect viral hepatitis-related liver cancer in HIV-infected patients (PI Jose D. Debes, University of Minnesota). The aims of the parent grant are to evaluate markers in peripheral blood to differentiate individuals with and without hepatocellular carcinoma in a Latin American population living with HIV and co-infected with viral hepatitis. For this supplement, the scientific focus aligns with the aims of the parent grant, as we propose to evaluate the impact of hepatitis C and HIV co-infection in the development of early-age HCC by estimating biological age via epigenetic modifications in DNA from peripheral blood. Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver and the second most common cause of cancer-related death worldwide. The risk of HCC is heightened in those infected with HIV as they are frequently co-infected with hepatitis B or C (HBV, HCV). Studies have consistently shown that HIV-positive individuals living with HCV develop HCC at younger ages than their HIV-negative counterparts and the mechanisms involved in such early cancer development as well as identification of those at risk are largely unknown. Estimation of biological age through evaluation of CpG methylation patterns (epigenetic clock) is becoming a powerful tool to understand the impact of infections in age acceleration, which is the difference between chronological and biological age. Indeed, individuals with HIV are known to have a biological age of 5- 11 years older than their HIV-negative counterparts. How this process affects cancer development in the setting of other co-infections such as HCV is currently unknown. In this supplement application, we propose to evaluate the epigenetic clock in individuals co-infected with HIV and HCV living in Latin America who developed hepatocellular carcinoma to estimate the impact of both infections in biological aging and cancer. Moreover, this project aims at understanding if cure of HCV decreases the impact of viral co-infection related to aging and HCC risk. This study will generate unique and innovative information related to risk of early-age HCC in HIV-infected individuals and provide the basis for a larger study addressing aging and cancer in co-infection.

摘要

项目成果

Clinical, Gender, Socioeconomic Characteristics and Outcomes of Individuals Receiving Hepatitis B Treatment in Ethiopia: 18-Month Follow-Up.

埃塞俄比亚接受乙型肝炎治疗的个人的临床、性别、社会经济特征和结果：18 个月的随访。

• DOI: 10.4269/ajtmh.23-0236
• 发表时间: 2023
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Tappata,Manaswita;Farah,Marina;Anugwom,Chimaobi;Bisrat,Eden;Seid,AmirS;Debes,JoseD
• 通讯作者: Debes,JoseD

MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort.

MBOAT7 RS641738变体与拉丁美洲队列中肝细胞癌的风险增加无关。

• DOI: 10.1007/s10620-023-08104-y
• 发表时间: 2023-11
• 期刊: DIGESTIVE DISEASES AND SCIENCES
• 影响因子: 3.1
• 作者: Goble, Spencer;Akambase, Joseph;Prieto, Jhon;Balderramo, Domingo;Ferrer, Javier Diaz;Mattos, Angelo Z.;Arrese, Marco;Carrera, Enrique;Groothuismink, Zwier M. A.;Oliveira, Jeffrey;Boonstra, Andre;Debes, Jose D.
• 通讯作者: Debes, Jose D.

Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans.

• DOI: 10.3390/cancers15184530
• 发表时间: 2023-09-12
• 期刊: CANCERS
• 影响因子: 5.2
• 作者: Ayoub, Alan;Anugwom, Chimaobi M.;Prieto, Jhon;Balderramo, Domingo;Ferrer, Javier Diaz;Mattos, Angelo Z.;Arrese, Marco;Carrera, Enrique;Groothuismink, Zwier M. A.;Oliveira, Jeffrey;Boonstra, Andre;Debes, Jose D.
• 通讯作者: Debes, Jose D.