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

摘要 本申请是对一份名为“催化研究”的补充公告的回应。 关于艾滋病毒对艾滋病毒携带者一生中衰老的影响的培训“，通过 对现有福格蒂国际中心艾滋病毒方案(艾滋病毒-老龄化2023S)的行政补充。 申请者的父母资助(R21TW012390)的标题是，检测病毒性肝炎相关肝脏的免疫简档 艾滋病毒感染者的癌症(皮何塞·D·德贝斯，明尼苏达大学)。家长助学金的目的是 外周血标志物在鉴别肝细胞癌患者中的价值 感染艾滋病毒并同时感染病毒性肝炎的拉丁美洲人口。就本增刊而言， 科学的重点与父母资助的目标一致，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学年龄与HIV合并感染在早期肝癌发生中的作用 外周血中DNA的修饰。 摘要肝细胞癌是肝脏最常见的恶性肿瘤，也是第二常见的恶性肿瘤。 全球与癌症相关的死亡原因。那些感染艾滋病毒的人罹患肝癌的风险更高。 经常合并感染乙肝或丙型肝炎(乙肝、丙型肝炎)。研究一直表明，艾滋病毒阳性者 携带丙型肝炎病毒的人比艾滋病毒阴性的人患肝癌的年龄更小， 参与这种早期癌症发展以及识别高危人群的机制在很大程度上 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 成为了解感染对年龄加速的影响的有力工具，这是不同之处 在时序年龄和生物学年龄之间。事实上，众所周知，艾滋病毒携带者的生物学年龄为5岁- 比艾滋病毒阴性的同龄人大11岁。这一过程如何影响癌症的发展 目前尚不清楚其他合并感染的情况，如丙型肝炎病毒。 在这项补充应用中，我们建议评估合并感染的个体的表观遗传学时钟。 与艾滋病毒和丙型肝炎病毒生活在拉丁美洲谁发展为肝细胞癌估计 这两种感染在生物衰老和癌症中的影响。此外，该项目旨在了解如果 治愈丙型肝炎病毒可减少与衰老和肝癌风险相关的病毒混合感染的影响。 这项研究将产生与HIV感染的早期肝癌风险相关的独特和创新的信息 并为一项更大规模的研究提供基础，以解决衰老和癌症合并感染的问题。

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.