MAPK8 and hepatocellular carcinoma: We have shown that in patients with chronic liver disease progression, HBV or HCV components and pro-inflammatory cytokine additively activate JNK to shift Smad phospho-isoform signaling from tumor-suppressive TβRI/pSmad3C pathway to carcinogenic JNK/pSmad3L pathway and fibrogenic pSmad2L/C pathway, accelerating liver fibrosis and increasing the risk of HCC (Fig. 3A).