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.

抽象的 该申请是为了响应：催化研究的补充公告。 以及培训艾滋病毒对艾滋病毒感染者衰老的影响的培训” 现有的Fogarty国际中心艾滋病毒计划（HIV-Aging2023S）的行政补品。 申请人的家长赠款（R21TW012390）的标题为“免疫分析”，可检测与病毒肝炎相关的肝脏 艾滋病毒感染患者的癌症（Pi Jose D.辩论，明尼苏达大学）。父母赠款的目的是 评估外周血中的标志物以区分有或没有肝细胞癌的个体 患有艾滋病毒的拉丁美洲人群，并与病毒肝炎共感染。为此补充 科学重点与父母赠款的目的保持一致，因为我们建议评估丙型肝炎的影响 通过表观遗传学估计生物年龄，在早期HCC开发中的HIV共同感染 外周血中的DNA修饰。 肝细胞癌（HCC）是肝脏中最常见的恶性肿瘤，第二常见 全球与癌症有关的死亡原因。在感染艾滋病毒的患者中，HCC的风险增加了 经常与乙型肝炎或C（HBV，HCV）共同感染。研究一直表明HIV阳性 患有HCV的人比他们的HIV阴性对应物发展了HCC的年龄较小 这种早期癌症发展涉及的机制以及对处于危险的鉴定的机制在很大程度上是 未知。通过评估CpG甲基化模式（表观遗传时钟）来估计生物年龄 成为了解感染在年龄加速中影响的强大工具，这是差异 在年代和生物年龄之间。实际上，已知艾滋病毒的个体的生物年龄为5-- 比他们的HIV阴性大11岁。这个过程如何影响癌症的发展 目前未知的其他共同感染（例如HCV）的设置。 在此补充应用中，我们建议评估共同感染的个体的表观遗传时钟 艾滋病毒和HCV生活在拉丁美洲，他们开发了肝细胞癌以估计 两种感染在生物衰老和癌症中的影响。此外，该项目旨在了解是否 HCV的治疗降低了与衰老和HCC风险有关的病毒共感染的影响。 这项研究将产生与HIV感染的早期HCC风险有关的独特而创新的信息 个人并为在共同感染中进行较大的研究提供了较大的研究。

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.

• 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.