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Hepatitis B (HBV) and C viruses have been classified as oncoviruses and are responsible for the majority of HCC cases, while the role of hepatitis D virus (HDV) in liver carcinogenesis has not been elucidated. HDV\/HBV coinfection is related to more severe liver damage than HBV mono\u2010infection and recent studies suggest that HDV\/HBV patients are at increased risk of developing HCC compared to HBV mono\u2010infected patients. HBV is known to promote hepatocarcinogenesis via DNA integration into host DNA, disruption of molecular pathways by regulatory HBV x (HBx) protein and excessive oxidative stress. Recently, several molecular mechanisms have been proposed to clarify the pathogenesis of HDV\u2010related HCC including activation of signalling pathways by specific HDV antigens, epigenetic dysregulation and altered gene expression. Alongside, ongoing chronic inflammation and impaired immune responses have also been suggested to facilitate carcinogenesis. Finally, cellular senescence seems to play an important role in chronic viral infection and inflammation leading to hepatocarcinogenesis. In this review, we summarize the current literature on the impact of HDV in HCC development and discuss the potential interplay between HBV, HDV and neighbouring liver tissue in liver carcinogenesis.<\/jats:p>","DOI":"10.1111\/liv.15253","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T06:27:59Z","timestamp":1648016879000},"page":"22-30","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Hepatocellular carcinoma: The virus or the liver?"],"prefix":"10.1111","volume":"43","author":[{"given":"Alkistis","family":"Papatheodoridi","sequence":"first","affiliation":[{"name":"Department of Clinical Therapeutics, Medical School of National and Kapodistrian University of Athens \u201cAlexandra\u201d General Hospital of Athens  Athens 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