The variant PNPLA3 148M has reduced hydrolase activity, and has been shown to promote the production of pro-fibrogenic cytokines, including CCL2 and CCL5, which stimulate HSC activation and therefore additionally promote inflammation and fibrosis in NAFLD/NASH [10,11,12]. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatohepatitis.