Author information

¹Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy.

²Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

³Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

⁴Department of Medical and Surgical Sciences, Università di Bologna, Bologna, Italy; Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

⁵Department of Medicine and Surgery, University of Enna 'Kore', Enna, Italy; Gastroenterology Unit, Umberto I Hospital, Enna, Italy.

⁶Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

⁷Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. Electronic address: antonio.facciorusso@virgilio.it.

Abstract

Background: Hepatocellular carcinoma (HCC) accounts for >90% of primary liver cancer cases, and chronic infections with hepatitis B virus (HBV) and hepatitis D virus (HDV) are major contributors.

Methods: A comprehensive literature review was conducted using the MEDLINE (PubMed) database, focusing on studies related to HBV, HDV, and HCC.

Results: HBV contributes to HCC through mechanisms like viral integration into the host genome, chronic inflammation, and immune modulation, leading to genomic instability and altered cell signaling. HDV exacerbates HBV-induced liver damage, accelerating fibrosis and cirrhosis, and significantly increasing HCC risk. Antiviral therapies and vaccinations have majorly reduced the burden of HBV-related HCC, but HDV remains challenging to treat due to limited therapeutic options. Emerging treatments like Bulevirtide showed promising results.

Conclusion: This review highlights the critical impact of HBV and HDV co-infections on HCC development, emphasizing the need for more effective therapeutic strategies. While advances in antiviral therapies have reduced the incidence of HBV-related HCC, the high burden of HDV-related complications persists. Future research should focus on improving treatments for HDV and understanding its unique contribution to HCC pathogenesis.