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 (Sm) 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 HCC-causing infections. To understand our data demonstrating synergistic interaction between chronic HBV and Sm infections, we will examine HBV clinical and immunological responses in the periphery and the liver in response to Sm treatment with praziquantel. Over time, liver Sm-related inflammation transitions from a Th1 to Th2 bias, and we hypothesize this transition may promote HBV replication. We will evaluate the dynamics of plasma HBV DNA during Sm treatment and correlate these with contemporaneous changes in plasma cytokines to characterize Th1 shifted inflammation. We also concurrently examine HBV specific CD4+ and CD8+ T cell responses, and measures of Sm treatment efficacy. Through investigation of liver biopsies on patients before and after SM treatment as well as with HCC, we anticipate confirming in humans that Sm is pro-carcinogenic and that Sm treatment only partially diminishes expression of pro-carcinogenic genes. HIV will be evaluated as a modifier of each relationship. Given our strong record, the proposed research has a high likelihood for successful contribution to reducing the burden and improving understanding of chronic infections and HCC in Africa.