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Figure 1. Progression from chronic liver injury to HCC. Persistent exposure of the liver to harmful stimuli (viral hepatitis, alcohol abuse, and NASH) induces necrosis of the hepatocytes and thus initiates compensatory regenerative processes. This leads to hepatocyte-based regeneration, a vicious circle of hepatocyte senescence and hepatic stellate cell activation with deposition of interstitial matrix and consecutive fibrosis formation up to liver cirrhosis occurs. The resulting genomic instability initiates the cascade of hepato-carcinogenesis from dysplastic nodules to the development of HCC. A stepwise accumulation of multiple events such as genetic rearrangements, somatic mutations, epigenetic alterations, and activation of various growth factor signaling pathways leads to tumor proliferation and metastasis. HCV: Hepatitis C virus; HBV: hepatitis B virus; HCC: hepatocellular carcinoma.