A novel frontier in the management of NASH-HCC is represented by the manipulation of the immune system through chimeric antigen receptor (CAR) T cells, vaccination using peptides or DNA, cytokine/chemokine antibody blockade, adoptive immune cell transfer and monoclonal antibody against PD-1 although large clinical trials are required to confirm their efficacy. This evidence concerns the gene PDCD1 and metabolic dysfunction-associated steatohepatitis.