Hepatocellular carcinoma: The virus or the liver?
Alkistis PapatheodoridiGeorgios PapatheodoridisPublished in: Liver international : official journal of the International Association for the Study of the Liver (2022)
Hepatocellular carcinoma (HCC) represents a major public health problem being one of the most common causes of cancer-related deaths worldwide. 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-infection and recent studies suggest that HDV/HBV patients are at increased risk of developing HCC compared to HBV mono-infected 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-related 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.
Keyphrases
- hepatitis b virus
- liver failure
- oxidative stress
- gene expression
- public health
- immune response
- dna methylation
- single molecule
- end stage renal disease
- dna damage
- systematic review
- circulating tumor
- newly diagnosed
- risk assessment
- cell free
- chronic kidney disease
- dendritic cells
- prognostic factors
- body mass index
- signaling pathway
- induced apoptosis
- small molecule
- ischemia reperfusion injury
- physical activity
- patient reported
- protein protein
- binding protein