Fig. 4

Oncogenic mechanisms of HBV and HCV in hepatocellular carcinoma. a HBV infection causes chromosomal abnormalities, mitotic defects, and increased genetic mutations. b HBx activates glycolysis via the NF-κB/HK2 pathway, and excess lactic acid enhances HCC proliferation through the PI3K/AKT pathway. c HBV evades T cell responses by enhancing the expression of PD-L1 in HCC cells, and its related factors construct an inflammatory microenvironment while the infection leads to ROS accumulation and triggers oxidative stress. d HBV promotes angiogenesis in HCC by increasing HIF-1α, HMGB1, and VEGF expression, and activates MAPK pathways to facilitate metastasis. e HBx protein upregulates p65 and HK2, downregulates TXNIP to enhance host cell glycolysis. f HCV promotes HCC proliferation by inhibiting EGFR degradation, activating Wnt/β-catenin signaling, inducing c-Myc and cyclin D1 expression, blocking K⁺ channels, and enhancing the expression of abnormal DNA polymerase. g HCV suppresses IFN signaling, promotes TGF-β1 secretion, and increases inhibitory receptor expression on immune cells, thereby dampening the immune response. h HCV infection enriches inflammatory factors in the TME, contributing to liver fibrosis. i HCV can enhance glycolysis, increase the accumulation of long-chain fatty acids, and interfere with insulin signaling. Blue part: HBV carcinogenic mechanism; Red part: HCV carcinogenic mechanism; Text in virus color: viral components; Black text: host cell components; Direct oncogenesis: a, b (HBV), f (HCV); Indirect oncogenesis: c, d (HBV), g–i (HCV). This figure was created with BioRender.com