Figure 1.

Liver disease progression: from steatosis to hepatocellular carcinoma. Schematic representation of the two-hit hypothesis and the progression of the disease, with characteristic H&E staining micrographs from each state of the pathology. A first hit leads an increased lipid accumulation in the liver, named steatosis. In a second hit reactive oxygen species (ROS), lipotoxicity, endoplasmic reticulum (ER) stress and mitochondrial dysfunction lead to non-alcoholic steatohepatitis (NASH) in 10%–30% patients. Sustained damage results in apoptosis, inflammation and extracellular matrix (ECM) deposition, leading to a fibrotic response and cirrhosis in 20% of patients. Finally, the 4%–27% of chronic patients can develop hepatocellular carcinoma (HCC).