From Viral Oncogenesis to Dual Checkpoint Blockade: A Comprehensive Review of Hepatocellular Carcinoma Biology, Treatment and Guideline Evolution

Ziming Qiao

doi:10.54254/2753-8818/2025.AU25990

Theoretical and Natural ScienceOpen access

From Viral Oncogenesis to Dual Checkpoint Blockade: A Comprehensive Review of Hepatocellular Carcinoma Biology, Treatment and Guideline Evolution

Research Article

Open Access

From Viral Oncogenesis to Dual Checkpoint Blockade: A Comprehensive Review of Hepatocellular Carcinoma Biology, Treatment and Guideline Evolution

Ziming Qiao ^1*

¹ Pennsylvania State University

^*Corresponding author: zpq5037@psu.edu

Published on 13 August 2025

TNS Vol.124

ISSN (Print): 2753-8826

ISSN (Online): 2753-8818

ISBN (Print): 978-1-80590-271-3

ISBN (Online): 978-1-80590-272-0

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Abstract

Hepatocellular carcinoma (HCC) is the leading primary liver cancer and remains one of the deadliest malignancies globally. Its incidence continues to rise, driven by chronic viral hepatitis in the Eastern countries and metabolic liver disease in the Western countries. Landmark phase III trials have transformed the landscape of systemic therapy: atezolizumab–bevacizumab, durvalumab–tremelimumab, and nivolumab–ipilimumab each deliver superior survival over sorafenib and are now first-line standards. Parallel studies are testing these agents in adjuvant, neoadjuvant, and locoregional combinations, signalling a shift toward earlier immunologic intervention. Yet the field still lacks validated biomarkers and globally harmonised treatment algorithms. This review compiles current evidence on worldwide epidemiology of HCC, key risk factors such as HBV, aflatoxin exposure and NAFLD, and the molecular pathways that drive hepatocarcinogenesis. It critically compares the design, efficacy and safety of major immunotherapy trials and summarises ongoing studies that combine systemic agents with surgery, ablation or transarterial chemo-embolisation. By mapping existing data to current unmet needs, this analysis highlights key opportunities for advancing biomarker-guided precision therapy and expanding access to novel treatments in resource-limited settings.

Keywords:

Hepatocellular carcinoma, Tremelimumab, Malignancies, Embolisation.

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References

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References

[5]. Khemlina, G., Ikeda, S., and Kurzrock, R. The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies. Molecular Cancer, vol. 16, 2017, article 149.

[6]. Liver and Intrahepatic Bile Ducts Fact Sheet. GLOBOCAN, gco.iarc.who.int/media/globocan/factsheets/cancers/11-liver-and-intrahepatic-bile-ducts-fact-sheet.pdf.

[7]. Pai, S. G., Carneiro, B. A., Mota, J. M., et al. Wnt/β-Catenin Pathway: Modulating Anticancer Immune Response. Journal of Hematology & Oncology, vol. 10, 2017, article 101.

[8]. Zhou, J., Sun, H., Wang, Z., et al. Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). Liver Cancer, vol. 12, no. 5, 2023, pp. 405–444.

[9]. Reig, M., Forner, A., Rimola, J., et al. BCLC Strategy for Prognosis Prediction and Treatment Recommendation: The 2022 Update. Journal of Hepatology, vol. 76, no. 3, 2022, pp. 681–693.

[13]. Kudo, M. Immuno-Oncology Therapy for Hepatocellular Carcinoma: Current Status and Ongoing Trials. Liver Cancer, vol. 8, no. 4, 2019, pp. 221–238.

[15]. Finn, Richard S., et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. New England Journal of Medicine 382.20 (2020): 1894-1905.

Cite this article

Qiao,Z. (2025). From Viral Oncogenesis to Dual Checkpoint Blockade: A Comprehensive Review of Hepatocellular Carcinoma Biology, Treatment and Guideline Evolution. Theoretical and Natural Science,124,7-18.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: AI for Healthcare: Advanced Medical Data Analytics and Smart Rehabilitation

ISBN: 978-1-80590-271-3(Print) / 978-1-80590-272-0(Online)

Editor: Alan Wang

Conference website: https://2025.icbiomed.org/auckland.html

Conference date: 17 October 2025

Series: Theoretical and Natural Science

Volume number: Vol.124

ISSN: 2753-8818(Print) / 2753-8826(Online)

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