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Hepatocellular carcinoma (HCC) represents a major and steadily increasing global health challenge as the most common primary liver malignancy and leading cause of death in cirrhotic patients. The only hope for curative treatment or significant increase in life expectancy is early detection. Once patients have progressed towards end-stage HCC, effective treatment options are extremely limited on the background of a very high degree of heterogeneity in clinical presentation and outcome. Experimental chronic liver injury and cancer have been used extensively to mimic the human disease. In particular, mouse studies have advanced the field due to the ability to easily manipulate the mouse genome and transcriptome for mechanistic evaluations. In addition, they offer the opportunity to screen new therapeutic strategies cost effectively and in quick high-throughput, large-scale formats. The most commonly used mouse models in HCC research can be categorized as chemotoxic, diet-induced, and genetically engineered models. It is important to note that no particular model mimics all features of a given HCC etiology or histological subtype, and each model poses advantages and disadvantages that need to be carefully considered.
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