Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study

doi:10.4254/wjh.120213

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Jun 27, 2026; 18(6): 120213
Published online Jun 27, 2026. doi: 10.4254/wjh.120213

Recurrence after surgery for hepatocellular carcinoma: “The seed and the soil” - a multicentre retrospective cohort study

Conner Blackmore, Ian Lockart, Geovanny Gandy, Yuen Kang Joseph Yeoh, Ciara Flynn, David S Prince, Gregory Dore, Mark Danta, Jacob George, Maryam Alavi, Yasser Farooque, Behzad Hajarizadeh, Miriam T Levy

Conner Blackmore, David S Prince, Miriam T Levy, Department of Gastroenterology, Liverpool Hospital, Liverpool 2170, New South Wales, Australia

Conner Blackmore, Ian Lockart, Geovanny Gandy, Yuen Kang Joseph Yeoh, Ciara Flynn, David S Prince, Mark Danta, Miriam T Levy, South Western Sydney Clinical School, Department of Medicine, University of NSW, Sydney 2000, New South Wales, Australia

Ian Lockart, Gregory Dore, Mark Danta, Department of Gastroenterology and Hepatology, St Vincents Hospital, Sydney 2000, New South Wales, Australia

Ian Lockart, Mark Danta, St Vincent’s Health Care Campus, School of Clinical Medicine, University of New South Wales, Sydney 2000, New South Wales, Australia

Geovanny Gandy, Department of Gastroenterology and Hepatology, Liverpool Hospital, Liverpool 2170, New South Wales, Australia

David S Prince, Miriam T Levy, Department of Gastroenteroiogy, Ingham Institute for Applied Medical Research, Sydney 2000, New South Wales, Australia

Gregory Dore, Maryam Alavi, Behzad Hajarizadeh, The Kirby Institute, University of New South Wales, Sydney 2000, New South Wales, Australia

Jacob George, Storr Liver Centre, Sydney 2145, New South Wales, Australia

Jacob George, Department of Gastroenterology, Westmead Institute for Medical Research, Sydney 2145, New South Wales, Australia

Jacob George, Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney 2145, New South Wales, Australia

Jacob George, School of Medicine, University of Sydney, Sydney 2000, New South Wales, Australia

Yasser Farooque, Department of Upper Gastrointestinal Surgery, Liverpool Hospital, Liverpool 2170, New South Wales, Australia

Author contributions: Blackmore C and Levy MT designed the study; Blackmore C, Lockart I, Yeoh YKJ, and Flynn C performed data acquisition; Blackmore C, Levy MT, and Hajarizadeh B performed data analyses; Blackmore C, Levy MT, and Gandy G drafted the manuscript; Blackmore C, Lockart I, Gandy G, Yeoh YKJ, Flynn C, Prince DS, Dore G, Danta M, George J, Alavi M, Farooque Y, Hajarizadeh B, and Levy MT revised the manuscript; and all authors reviewed and approved the final manuscript.

Institutional review board statement: The study protocol was approved by the Human Research Ethics Committee of St Vincent’s Hospital, Sydney, Australia (approval No. 2025/ETH01121), with additional approvals from local ethics committees at participating study sites. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Informed consent statement: Given the retrospective nature of the study, the requirement for individual patient consent was waived by the committees.

Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: All data generated or analysed during this study are included within this article. De-identified datasets supporting the findings of this study are available from the corresponding author on reasonable request, in accordance with institutional ethics approval (Ethics Approval No. 2025/ETH01121).

Corresponding author: Miriam T Levy, Associate Professor, Department of Gastroenterology, Liverpool Hospital, Corner Elizabeth and Goulburn St, Liverpool 2170, New South Wales, Australia. miriam.levy@health.nsw.gov.au

Received: February 24, 2026
Revised: March 16, 2026
Accepted: April 14, 2026
Published online: June 27, 2026
Processing time: 122 Days and 16.3 Hours

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Liver resection provides a curative option, though recurrence following resection remains a major clinical challenge, as adjuvant therapies evolve, and preservation of liver function becomes increasingly important.

AIM

To evaluate factors associated with HCC recurrence in a real-world setting.

METHODS

We retrospectively reviewed records of patients with HCC who underwent primary liver resection at three tertiary referral hospitals between January 2008 and May 2022. Baseline patient and tumour characteristics were assessed. Risk factors for recurrence were analysed using multivariate Cox regression.

RESULTS

In this cohort, 235 patients underwent surgical resection for HCC. Median survival was 80.9 months. HCC recurred in 94 (40%) patients with median time to recurrence 18.8 months (interquartile range: 8.6-35). An albumin-bilirubin (ALBI) grade of ≥ 2 [adjusted hazard ratio (aHR): 2.02 (1.27-3.21), P = 0.003], the presence of cirrhosis [aHR: 2.03 (1.27-3.25), P = 0.003], and Barcelona Clinic Liver Cancer (BCLC) stage B/C [aHR: 2.23 (1.23-4.03) P = 0.008] were independently associated with increased risk of recurrence. When combining these risk factors, the adjusted HR for recurrence was 2.73 (1.57-4.75), 4.32 (2.29-8.12) and 7.52 (2.47-22.93) in those with 1, 2, or 3 factors compared to those with 0 (P < 0.001).

CONCLUSION

HCC recurrence following primary liver resection was independently associated with cirrhosis, ALBI grade ≥ 2 and BCLC stage B/C. The seed (the liver cancer as reflected by BCLC stage), and the soil (the liver function and presence or absence of cirrhosis) are relevant considerations for recurrence prediction.

Keywords: Hepatocellular carcinoma; Prognostic prediction; Surgery; Recurrence; Albumin-bilirubin grade

Core Tip: Recurrence following curative liver resection for hepatocellular carcinoma (HCC) remains a major clinical challenge. In this multicentre retrospective cohort study, cirrhosis, albumin-bilirubin grade ≥ 2, and Barcelona Clinic Liver Cancer stage B/C were independently associated with recurrence. These findings highlight the importance of both tumour burden and underlying liver function when estimating postoperative recurrence risk. Improved preoperative risk stratification may support patient counselling and multidisciplinary decision-making in the management of HCC.