The Obesity Paradox in Hepatocellular Carcinoma: Insights from Continuous and Interaction-Based Analyses of Body Mass...

Background/Objectives: The prognostic significance of body mass index (BMI) in hepatocellular carcinoma (HCC) remains controversial, and whether the obesity paradox may reflect tumor biology or host-related factors is unclear. This study evaluated the association between BMI and survival after curative hepatic resection using continuous and interaction-based analyses. Methods: We retrospectively analyzed 1349 patients who underwent curative hepatic resection for HCC between 2004 and 2021. BMI was assessed both categorically (low (<18.5 kg/m²), normal (18.5-24.9 kg/m²), and high (≥25 kg/m²)) and as a continuous variable. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier methods and multivariable Cox proportional hazards models. Interaction terms were incorporated to examine whether the prognostic effect of BMI varied across clinically relevant subgroups defined by tumor differentiation, tumor size, tumor number, and alpha-fetoprotein level. Results: OS differed significantly across BMI categories (log-rank p < 0.001), whereas differences in RFS were modest. At 3 years, estimated OS rates were 88%, 82%, and 62% in the high, normal, and low BMI groups, respectively. In multivariable analysis, higher BMI as a continuous variable was independently associated with improved OS (hazard ratio per 1-unit increase, 0.87; 95% confidence interval, 0.79-0.95; p = 0.005), but not with RFS. Subgroup analyses demonstrated a consistent protective association between BMI and OS without significant interactions across tumor-related factors. Conclusions: Higher BMI is independently associated with improved overall survival after hepatic resection for HCC, irrespective of tumor biology. These findings support a host-related explanation for the obesity paradox in surgically treated HCC.