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

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.