AREA A
In the Western world metabolic syndrome leading to fatty liver disease, steatohepatitis, and liver cirrhosis as well as chronic Hepatitis C Virus infection are the leading causes of both types of liver cancer (HCC and ICC). The biological drivers of HCV-induced carcinogenesis encompass all steps ranging from virus entry and replication to the activation of cellular and immunological responses of the host, which together result in a “field carcinogenic effect” that predisposes the HCV infected liver to the formation of HCC and ICC and its precursor lesions. It is still debated, whether and to which extent curative HCV treatment may reduce the risk of liver cancer development, but it is clear that Hepatitis C and HCV-induced liver cancer will continue to rise for years to come and thus necessitate continued efforts to understand, prevent, and treat HCV-induced liver cancer. NASH is a premalignant condition and the molecular pathways involved are much less understood but will be elucidated in relevant in vivo systems. A detailed understanding of the protumorigenic mechanisms of HCV and NASH induced carcinogenesis and their common denominator, chronic inflammation, especially related to DAMP-RAGE signaling and TNF-induced mechanisms, are therefore of key relevance for primary and secondary prevention and will be the central research focus of area A projects.