Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most common causes of chronic liver disease worldwide. It has two principal phenotypes: non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH). NASH can progress to cirrhosis in 15—20% of subjects and is also a risk factor for hepatocellular cancer (HCC). The increasing incidence of HCC has been linked to the growing epidemic of obesity and NASH. By definition, NAFLD occurs in individuals who do not consume harmful amounts alcohol.
Recent studies have identified that, at a cellular level, similar pathophysiological pathways are frequently turned on in alcoholic and non-alcoholic steatohepatitis. Several mechanisms have been implicated in the pathogenesis of cell injury in NASH. These include free fatty acid induced cell toxicity (lipotoxicity), oxidative stress, endoplasmic reticulum stress (ER stress) and activation of the innate immune system, and cytokine-mediated cellular changes. Free fatty acids can cause cellular injury in several ways, including direct activation of inflammatory pathways, ER stress and activation of the innate immune system via Toll-like receptors.

References

1.Sanyal AJ. Gastroenterol. 2015;39 Suppl 1:S46–S50.