Studying the contribution of an underlying liver disease to the development and progression of liver cancer: from NASH to HCC

The incidence of liver cancer, more specifically of Hepatocellular Carcinoma (HCC), which is the most common type of liver cancer, has been increasing worldwide. Such increase is directly correlated with an increased incidence of underlying chronic liver diseases, like Non-alcoholic fatty liver disease (NAFLD) and Non-alcoholic steatohepatitis (NASH). The mechanisms involved in the pathophysiology of NASH and HCC have been studied, however the NASH to HCC progression and the contribution of NASH in NASH associated hepatocarcinogenesis still remains poorly understood. A potential reason is the lack of animal models that recapitulate the clinical stages of human liver cancer, which in the majority of the cases develops in livers with underlying chronic liver diseases, such as NASH. The absence of “human-like” models can also result in an unreliably prediction of clinical utility of therapies in early phases of clinical trials, which could explain the lack of successful therapeutic trials for NASH associated HCC. Thus, the aim of this project is to develop a mouse model that recapitulates the key features of human NASH-associated HCC in order to establish a useful experimental tool to study NASH to HCC progression, as well as the contribution of underlying NASH in HCC development and progression.