Unraveling the obesity paradox in hepatocellular carcinoma: relative role of elevated body mass index on detrimental effects of postoperative complications

Miho Akabane; Jun Kawashima; Abdullah Altaf; Selamawit Woldesenbet; François Cauchy; Federico Aucejo; Irinel Popescu; Minoru Kitago; Guillaume Martel; Francesca Ratti; Luca Aldrighetti; George A Poultsides; Yuki Imaoka; Andrea Ruzzenente; Itaru Endo; Ana Gleisner; Hugo P Marques; Sara Oliveira; Jorge Balaia; Vincent Lam; Tom Hugh; Nazim Bhimani; Feng Shen; Timothy M Pawlik

doi:10.1016/j.hpb.2025.05.005

Unraveling the obesity paradox in hepatocellular carcinoma: relative role of elevated body mass index on detrimental effects of postoperative complications

HPB (Oxford). 2025 Aug;27(8):1103-1112. doi: 10.1016/j.hpb.2025.05.005. Epub 2025 May 28.

Authors

Miho Akabane¹, Jun Kawashima¹, Abdullah Altaf¹, Selamawit Woldesenbet¹, François Cauchy², Federico Aucejo³, Irinel Popescu⁴, Minoru Kitago⁵, Guillaume Martel⁶, Francesca Ratti⁷, Luca Aldrighetti⁷, George A Poultsides⁸, Yuki Imaoka⁸, Andrea Ruzzenente⁹, Itaru Endo¹⁰, Ana Gleisner¹¹, Hugo P Marques¹², Sara Oliveira¹², Jorge Balaia¹², Vincent Lam¹³, Tom Hugh¹⁴, Nazim Bhimani¹⁴, Feng Shen¹⁵, Timothy M Pawlik¹⁶

Affiliations

¹ Department of Surgery, The Ohio State University, Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
² Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France.
³ Department of General Surgery, Cleveland Clinic Foundation, OH, USA.
⁴ Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania.
⁵ Department of Surgery, Keio University, Tokyo, Japan.
⁶ Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.
⁷ Department of Surgery, Ospedale San Raffaele, Milan, Italy.
⁸ Department of Surgery, Stanford University, Stanford, CA, USA.
⁹ Department of Surgery, University of Verona, Verona, Italy.
¹⁰ Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.
¹¹ Department of Surgery, University of Colorado, Denver, CO, USA.
¹² Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal.
¹³ Department of Surgery, Westmead Hospital, Sydney, NSW, Australia.
¹⁴ Department of Surgery, School of Medicine, The University of Sydney, Sydney, NSW, Australia.
¹⁵ The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
¹⁶ Department of Surgery, The Ohio State University, Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. Electronic address: Tim.Pawlik@osumc.edu.

PMID: 40527693
DOI: 10.1016/j.hpb.2025.05.005

Abstract

Background: The "obesity paradox" suggests higher body mass index (BMI) may correlate with better long-term outcomes in cancers. The impact of BMI on hepatocellular carcinoma (HCC) resection, regarding postoperative complications, remains unclear. We examined the interplay between BMI and complications on recurrence-free survival (RFS) among patients undergoing HCC resection.

Methods: Patients undergoing hepatectomy for HCC (2000-2023) were identified from an international database. Kaplan-Meier and Cox analyses assessed the protective impact of high BMI on RFS, considering interactions with complications.

Results: Among 1,588 patients (median BMI: 25.2 kg/m²; BMI > 25.0:793, BMI ≤ 25.0:795), 560 (35.3%) experienced complications. BMI > 25.0kg/m² was linked to better 5-year RFS than BMI ≤ 25.0kg/m² (50.3% vs 45.4%; p = 0.006). Patients without complications had better 5-year RFS than those with complications (51.7% vs 40.7%; p < 0.001). Among patients without complications, RFS was comparable among BMI groups (52.9% vs 50.6%; p = 0.215), but among patients with complications BMI > 25.0kg/m² was associated with better RFS (45.6% vs 34.2%; p < 0.001). Patients with complications and BMI > 25.0 kg/m² had RFS comparable to patients without complications, regardless of BMI. Multivariable analysis identified complications (HR:1.31 [1.08-1.60]; p = 0.007) as a predictor of worse RFS, while BMI > 25.0 kg/m² (HR: 0.79 [0.68-0.96]; p = 0.020) was protective. Spline analysis demonstrated recurrence risk declined with increasing BMI among patients with complications, crossing below 1 around 25.0kg/m². Stratifying the complication cohort (BMI ≤ 25.0/25.0-30.0/>30.0 kg/m²) demonstrated dose-dependent RFS improvement (p = 0.005).

Conclusion: High BMI correlated with better RFS following HCC resection among patients with complications. Concerns about complications should not deter surgery among high-BMI patients.

MeSH terms

Aged
Body Mass Index*
Carcinoma, Hepatocellular* / complications
Carcinoma, Hepatocellular* / mortality
Carcinoma, Hepatocellular* / pathology
Carcinoma, Hepatocellular* / surgery
Databases, Factual
Disease-Free Survival
Female
Hepatectomy* / adverse effects
Hepatectomy* / mortality
Humans
Kaplan-Meier Estimate
Liver Neoplasms* / complications
Liver Neoplasms* / mortality
Liver Neoplasms* / pathology
Liver Neoplasms* / surgery
Male
Middle Aged
Obesity Paradox
Obesity* / complications
Obesity* / diagnosis
Obesity* / mortality
Postoperative Complications* / epidemiology
Postoperative Complications* / etiology
Postoperative Complications* / mortality
Proportional Hazards Models
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome