The Changing Face of Hepatitis Delta Virus Associated Hepatocellular Carcinoma
1
Gastroenterology Department, Hospital Prof. Doutor Fernando Fonseca, 2720-276 Amadora, Portugal
2
Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
3
Gastroenterology Department, Hospital de Vila Franca de Xira, 2600-009 Vila Franca de Xira, Portugal
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(22), 3723; https://doi.org/10.3390/cancers16223723
Submission received: 23 July 2024
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Revised: 22 September 2024
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Accepted: 1 November 2024
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Published: 5 November 2024
(This article belongs to the Section Cancer Epidemiology and Prevention)
Simple Summary
Hepatitis B virus (HBV)—hepatitis delta virus (HDV) coinfection accounts for an estimated 8–10% of cases of hepatocellular carcinoma (HCC) worldwide. Recent meta-analyses suggest that HDV increases the risk of HCC associated with HBV, but its pathogenic role remains poorly elucidated. HCC related to HBV–HDV coinfection tends to be diagnosed by surveillance but in the background of severe liver dysfunction, which has therapeutic implications, with a high rate of liver transplantation, and high mortality in patients not eligible for liver transplantation.
Abstract
Hepatitis delta virus (HDV) infection requires the presence of hepatitis B virus (HBV), and chronic HBV–HDV coinfection is considered the most severe form of viral hepatitis. When compared with HBV mono-infection, HBV–HDV coinfection is associated with higher rates of liver cirrhosis and hepatocellular carcinoma (HCC). In this review, we aim to elucidate the complex relationship between HDV infection and the development of HCC. The exact mechanisms underlying the carcinogenic potential of HDV remain to be fully elucidated. Evidence suggests that HDV has both indirect and direct oncogenic effects. Indirect effects promote accelerated progression to liver cirrhosis, which results in a different tumor microenvironment. Direct oncogenic effects are suggested by a distinct molecular signature. The recent epidemiological data regarding HBV–HDV coinfection should make us reconsider the HCC screening strategy, with special focus in younger non-cirrhotic patients. Finally, treating HCC in patients with chronic HDV poses unique challenges due to the complex interplay between HBV and HDV and the severity of liver disease. An in-depth understanding of the epidemiology and pathophysiology of HDV infection and carcinogenesis is essential to improve disease management in this high-risk population.
