Preoperative BMI and long-term survival in NAFLD-associated hepatocellular carcinoma: A multicenter study revealing a paradox.

e16262 Background: As non-alcoholic fatty liver disease (NAFLD) emerges as a key factor in hepatocellular carcinoma (HCC) development, exacerbated by the global obesity epidemic, the prognostic role of body mass index (BMI) in NAFLD-HCC patients undergoing surgical resection remains unclear. This study aims to elucidate the impact of preoperative BMI on long-term outcomes after hepatectomy in patients with NAFLD-HCC, offering insights for more personalized treatment strategies. Methods: In this multicenter retrospective study, patients with early-stage (BCLC stage 0/A) NAFLD-HCC who underwent curative hepatectomy between 2009 and 2022 were analyzed. Based on preoperative BMI, patients were classified into lean ( < 23.0 kg/m 2 ), overweight (23.0-27.4 kg/m 2 ), and obese (≥ 27.5 kg/m 2 ) categories. The primary endpoints, overall survival (OS) and recurrence-free survival (RFS), were compared across these BMI groups. Results: This large multicenter cohort comprised 309 early-stage NAFLD-HCC patients: 66 lean, 176 overweight, and 67 obese. Liver-, tumor-, and surgery-related characteristics were similar across groups. Lean patients exhibited significantly lower 5-year OS and RFS (55.4% and 35.1%, respectively) compared to overweight patients (71.3% and 55.6%, P = 0.017 and P = 0.002), with outcomes comparable to obese patients (48.5% and 38.2%, P = 0.939 and P = 0.442). Multivariable Cox-regression analysis revealed lean BMI, but not obese BMI, as an independent predictor of decreased OS (HR: 1.69; 95%CI: 1.06-2.71; P = 0.029) and RFS (HR: 1.72; 95% CI: 1.17-2.52; P = 0.006). Conclusions: This study challenges conventional perceptions of BMI in cancer prognosis, revealing that lean NAFLD-HCC patients have poorer long-term surgical outcomes compared to their overweight and obese counterparts. These findings underscore the need for a nuanced understanding of BMI’s role in NAFLD-HCC management and prompt further investigation into the underlying biological mechanisms of this paradox.