The “two hits” hypothesis. Transformation from NAFLD to NASH can be explained by the so called “two hit” hypothesis. The “first hit consists of the intrahepatic accumulation of fatty acids, which is closely associated with insulin resistance, and which increases the susceptibility of hepatocytes to secondary injuries or insults (oxidative stress, mitochondrial dysfunction, overproduction and the release of pro-inflammatory cytokines, and the endotoxin-mediated activation of the innate immune response).
Giorgio et al. BMC Pediatrics 2013 13:40 doi:10.1186/1471-2431-13-40