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  • Review Article
  • Published:

Improving surgical treatments for hepatocellular carcinoma

Nature Reviews Gastroenterology & Hepatology volume 23, pages 208–226 (2026)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Curative-intent treatments offer the best long-term outcomes for selected patients. However, recurrence rates after resection approach 70% at 5 years, and access to transplantation remains limited by donor scarcity and stringent eligibility criteria. Emerging data reveal that recurrence is a reflection of underlying tumour biology, immune evasion and microenvironmental permissiveness. Advances in immunogenomic profiling, liquid biopsy and functional imaging are reshaping the concept of surgical eligibility, enabling biological risk stratification beyond conventional staging. At the same time, innovations in perioperative immunotherapy, graft preservation using machine perfusion and integrated multidisciplinary care are expanding the boundaries of curative treatment. These developments herald a shift from static criteria to dynamic, biology-driven paradigms that personalize surgical and transplant strategies. In this Review, we examine the evolving landscape of surgical treatment for HCC. We highlight the limitations of current selection frameworks, discuss how biological insights can inform resection and transplant decision-making and explore the role of perioperative and neoadjuvant therapies in reducing the recurrence of disease. Finally, we outline a future precision oncology model that integrates tumour genomics, immune phenotype and regenerative biology to improve outcomes in patients undergoing curative-intent treatment for HCC.

Key points

  • Curative-intent surgery for hepatocellular carcinoma — liver resection, ablation and liver transplantation — offers the best chance of long-term survival; however, recurrence remains common after resection or ablation, and access to transplantation is limited.

  • Traditional anatomical criteria for surgical selection are increasingly being replaced by biology-informed frameworks, incorporating tumour markers, immune profiling and functional imaging to assess risk and optimize outcomes.

  • Biological resectability, defined by tumour behaviour, regenerative capacity and microenvironmental permissiveness, is emerging as a more accurate predictor of surgical success than tumour size or number alone.

  • Machine perfusion technologies and expanded listing criteria are widening transplant access for select patients beyond conventional thresholds, including those with multifocal disease or portal vein tumour thrombosis.

  • Recurrence after curative surgery reflects complex tumour–immune–liver interactions, including micrometastatic persistence, immune escape and regenerative signalling, offering targets for perioperative intervention.

  • Perioperative immunotherapy and liquid biopsy technologies represent promising strategies to reduce recurrence and personalize care, but require further evaluation in prospective trials and integrated multidisciplinary frameworks.

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Fig. 1: BCLC algorithm.
Fig. 2: Redefining resectability in hepatocellular carcinoma: from anatomical to biology-informed criteria.
Fig. 3: Mechanisms and phenotypes of HCC recurrence.
Fig. 4: Immunological dynamics of the perioperative window in HCC.

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Acknowledgements

A.K.M. is supported by a clinical research training fellowship from the Medical Research Council (MR/Z50502X/1). The views expressed in this manuscript are solely those of the authors and do not reflect those of the Medical Research Council or affiliated institutions.

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Author notes

  1. These authors jointly supervised this work: Derek A. Mann, Steven A. White.

Authors and Affiliations

  1. Department of Hepato-Pancreato-Biliary and Transplant Surgery, Freeman Hospital, Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, UK

    Abdullah K. Malik & Steven A. White

  2. Newcastle Fibrosis Research Group, Newcastle University, Newcastle upon Tyne, UK

    Abdullah K. Malik & Daniel Geh

  3. Department of Liver Medicine, Freeman Hospital, Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, UK

    Daniel Geh & Derek A. Mann

  4. School of Cancer Sciences, University of Glasgow, Glasgow, UK

    Thomas R. Jeffry Evans

  5. Department of Hepato-Pancreato-Biliary and Transplant Surgery, National Cancer Centre Singapore and Singapore General Hospital, Singapore, Singapore

    Pierce K. H. Chow

  6. Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore

    Pierce K. H. Chow

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  1. Abdullah K. Malik
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Contributions

A.K.M. and D.A.M. researched data for the article. All authors contributed substantially to discussion of the content. A.K.M., D.A.M. and S.A.W. wrote the article. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to Abdullah K. Malik.

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Nature Reviews Gastroenterology & Hepatology thanks Phillipe Abreu, Arno Kornberg and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Malik, A.K., Geh, D., Jeffry Evans, T.R. et al. Improving surgical treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 23, 208–226 (2026). https://doi.org/10.1038/s41575-025-01143-y

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