1 Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2 Hepatology Section, Gastroenterology Department, Hospital del Mar, IMIM, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
3 Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
4 Denotes co-senior authorship.
5 Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, CIBERehd, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain.
6 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain.
Hepatitis delta virus (HDV) is a small defective virus that needs hepatitis B virus (HBV) to replicate and propagate. HDV infection affects 20-40 million people worldwide and pegylated interferon (PegIFN) is the only recommended therapy. There is limited data on the contribution of HDV infection to HBV-related liver disease or liver cancer. Evidence from retrospective and cohort studies suggests that HBV/HDV coinfection accelerates progression to cirrhosis and is associated with an increased risk of hepatocellular carcinoma (HCC) development compared to HBV monoinfection. Although the life cycle of HDV is relatively well known, there is only ancillary information on the molecular mechanisms that can drive specific HDV-related oncogenesis. No thorough reports on the specific landscape of mutations or molecular classes of HDV-related HCC have been published. This information could be critical to better understand the uniqueness, if any, of HDV-related HCC and help identify novel targetable mutations. Herein, we review the evidence supporting an oncogenic role of HDV, the main reported mechanisms of HDV involvement and their impact on HCC development.