A model combining clinical (age, sex, ALT, HOMA-IR, and sarcopenia), genomic (PNPLA3 rs738409), and metabolomic (PC ae C40:6, lysoPC a C18:2, SM C24:0, and tyrosine) parameters achieved the highest c-index (0.948) for the prediction of high-risk NASH. Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.