Liver Neoplasms

The main established causes described in the grounding are chronic hepatitis B virus infection and hepatitis C virus infection. Non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is also described as an increasingly frequent risk factor in Western populations.

The grounding indicates that hepatocellular carcinoma progression is modulated by the immune system and that the disease involves tumor microenvironment effects, signal transduction, epithelial-mesenchymal transition, gene expression regulation, glycolysis, drug resistance, and tumor escape. It also notes that non-alcoholic steatohepatitis-associated hepatocellular carcinoma has a unique molecular pathogenesis and that some cases harbor potentially actionable mutations.

Chronic infection with hepatitis B virus or hepatitis C virus increases risk. Non-alcoholic steatohepatitis, metabolic syndrome, and diabetes mellitus are also described as risk factors, and the broader liver-disease literature links liver cancer burden to cirrhosis-related disease.

For advanced hepatocellular carcinoma, systemic therapy has included antiangiogenic tyrosine kinase inhibitors such as sorafenib, regorafenib, and lenvatinib. Immunotherapy is also part of current management, including immune checkpoint inhibitors such as pembrolizumab and camrelizumab, and anti-VEGF/PD-L1-based combinations such as bevacizumab with checkpoint blockade are described as standard first-line therapy in the supplied reviews. The guidelines also note surgery, transplant, and intra-arterial therapies as treatment modalities used in hepatobiliary cancers.