PNPLA3 and metabolic dysfunction-associated steatohepatitis: As third aim, PNPLA3 genetic variant I148M has been strongly associated to progression of liver diseases (NASH) and liver fibrosis development.12, 13, 15, 16, 17, 41, 42 In this regard, lipids mediate directly or indirectly activation of intracellular pathways responsible of hepatocellular stress and innate immune system‐mediated inflammation, a condition called lipotoxicity.