Molecular and Clinical Features of Hepatocellular Carcinoma in Patients with HBV-HDV Infection

Molecular interactions and oncogenic mechanisms occurring in the HCC microenvironment associated with chronic HBV-HDV infection. Both immune cell impairment and stimulation of pro-oncogenic intracellular signaling pathways are involved in CHB- and CDH-driven hepatocarcinogenesis. Through the release of TGF-β and IL-10, M2 macrophages, MDSCs and tumor cells inhibit the antitumor functions of immune effector cells, promoting tumor immune escape. HBx upregulates Wnt/β-catenin signaling and promotes survivin protein synthesis, supporting tumor cell proliferation and preventing apoptosis. Synergistically, L-HDAg and HBx trigger the JNK/c-Jun and SRE/c-fos cascades, both of which are involved in cancer cell growth, proliferation and survival. The integration of HBV-DNA into the host genome and the overproduction of ROS, triggered by HBx, L-HDAg and S-HDAg, promote DNA damage and genomic instability. ROS also promote cancer cell survival, angiogenesis and invasiveness through upregulation of the NF-ĸB pathway, which is also stimulated by L-HDAg in a TNFα-dependent manner, and STAT-3 signaling, which is further activated by Th17 (via IL-22), pre-malignant cells and Kupffer cells (via IL-6). Image created with Biorender.com.

Publication

Molecular and Clinical Features of Hepatocellular Carcinoma in Patients with HBV-HDV Infection. (2023) Federico Costante, et al. J Hepatocell Carcinoma. 2023;10:713-724. Figure: F1. All organisms Homo sapiens Danio rerio

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