Viral Oncogenesis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) ranks among the most prevalent and lethal cancers worldwide, with chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) accounting for a substantial proportion of cases. Viral oncogenesis in HCC encompasses both direct and indirect mechanisms. Direct effects include integration of viral DNA into the host genome (in the case of HBV), expression of viral oncoproteins (such as HBx and HCV core), and the resultant activation of signalling pathways that drive cell proliferation, inhibit apoptosis and promote genomic instability. Indirectly, persistent viral infection elicits chronic inflammation, oxidative stress and cycles of hepatocyte death and regeneration, creating a microenvironment conducive to malignant transformation. Epigenetic alterations, including DNA methylation and histone modification, further dysregulate gene expression and may persist as an ‘epigenetic signature’ even after viral clearance. Immune escape mechanisms, such as upregulation of inhibitory checkpoint molecules and suppression of antiviral T-cell responses, allow infected hepatocytes to evade immune surveillance. Emerging data also highlight the role of gut–liver axis perturbations and microbiota-derived metabolites in modulating oncogenic processes. Understanding these interwoven pathways has underpinned the development of targeted therapies, immunotherapeutic approaches and surveillance strategies aimed at mitigating the global burden of viral HCC.

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Viral Oncogenesis in Hepatocellular Carcinoma publication trend

The graph below shows the total number of articles in viral oncogenesis in hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).

Technical terms

Oncogenesis: The process of tumour formation and malignant transformation of normal cells.

Hepatocellular carcinoma (HCC): A primary liver cancer arising from hepatocytes, often in the context of chronic liver disease.

Viral integration: The insertion of viral genetic material into the host genome, leading to genomic instability and dysregulated gene expression.

Epigenetic modifications: Reversible changes to DNA or histone proteins that alter gene expression without modifying the nucleotide sequence.

Direct‐acting antivirals (DAAs): Medications that target specific steps in the hepatitis C virus life cycle to achieve viral eradication.

References

1. The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions. MedComm (2025).
2. Hepatitis C virus and hepatocellular carcinoma: carcinogenesis in the era of direct-acting antivirals. Current Opinion in Virology (2024).
3. The direct and indirect roles of HBV in liver cancer: prospective markers for HCC screening and potential therapeutic targets. The Journal of Pathology (2014).
4. Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals. PLOS Genetics (2019).
5. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget (2016).