The presence of the I148M PNPLA3 mutant HSCs did not enhance the fibrotic phenotype in the in vitro NASH model, and this observation aligns with the findings of Bruschi et al., who also showed the mutant PNPLA3 protein to affect the pro‐inflammatory and steatotic state of HSCs.35 The I148M PNPLA3 mutation had the most profound effects in the presence of LPS challenge, suggesting a possible combinatorial effect between leaky gut (leading to LPS release) and the I148M PNPLA3 mutation in patients as two major risk factors promoting NAFLD/NASH progression. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatohepatitis.