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

摘要

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.