Antiviral treatment as prevention for HBV- and HBV/HIV-associated hepatocellular carcinoma

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Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live longer, the HCC burden may increase. In prior studies, our team identified chronic infection with hepatitis B and C viruses (HBV, HCV), HIV and Schistosomiasis mansoni as independent risk factors for HCC. Compared to the US, HCC in sub-Saharan Africa occurs at younger age and more advanced stage with survival of only months. Proposed is an East and West African partnership between colleagues at Makerere University in Uganda, Fann University in Senegal and Johns Hopkins University focused on HIV and hepatocellular carcinoma (HCC) in Africa: The H2A Consortium. Building on long-standing collaborative research, mentoring and clinical activities in both countries, our overarching goal is to reduce the heavy burden of HCC in sub- Saharan Africa. We advocate investigating cancer interception strategies using appropriate medical treatments to interrupt or reverse the impact of these HCC-causing infections. Consortium activities are designed to enhance both the clinical, population and translational research infrastructure and individual African investigator capacity to conduct high-level, collaborative investigation of HIV, chronic infections and HCC. In this project, we will form a large, prospective cohort of HBV and HBV/HIV co-infected persons with balanced recruitment from both Uganda and Senegal. Guideline-appropriate antiviral treatment against HBV will be initiated and HCC surveillance with ultrasound and alpha-fetoprotein performed. Baseline and six-month study visits will collect questionnaire, clinical, ultrasound, and elastography data. We will define clinical outcomes of HBV treatment in terms of reduced standard and novel viral biomarkers, stabilization and regression of liver fibrosis, and reduced incidence of HCC. In parallel, using a novel albumin adductomics approach, we will investigate changes in oxidative stress pathways and identify novel biomarkers relevant for both HBV and HIV infections. For each of these analyses, HIV co-infection is evaluated as a key effect modifier. The impact of these studies will be to inform treatment and screening approaches and potentially identify novel biomarkers for guiding HBV management and HCC prevention.