From the Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
The major etiologic factors for hepatocellular carcinoma (HCC), including chronic hepatitis B and C virus infections and nonalcoholic fatty liver disease, are now well established by epidemiologic investigations. The mechanisms by which these factors result in HCC have been extensively investigated but have not, to date, resulted in the development of specific therapeutic interventions. Other frequently occurring dysregulated pathways, including the Wnt/β-catenin signaling pathway, are proving difficult to target, but there are early suggestions that patients with "MET-high" HCC may benefit from the c-MET inhibitor tivantinib. Chronic inflammation and consequent cell damage and regenerative proliferation are common to all etiologic factors, and emerging evidence suggests that anti-inflammatory agents such as aspirin deserve further investigation as preventive agents.