In advanced MASH in humans and mice, IL21 is activated through the IL-21R-STAT1-c-Jun/c-Fos-IgA regulatory pathway, leading to the induction of immunosuppressive IgA+ B cells and the accumulation of IgA-producing plasma cells, which inhibit anti-tumour cytotoxic CD8+ T cells through the expression of PD-L1 and IL-10, thus facilitating the emergence of HCC (Sutti and Albano, 2020; Xie et al., 2024). The gene discussed is CD8A; the disease is metabolic dysfunction-associated steatohepatitis.