Long-term outcomes following hepatectomy in patients with lean non-alcoholic fatty liver disease-associated hepatocellular carcinoma versus overweight and obese counterparts: A multicenter analysis

Background & aims With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals. Methods A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m2), overweight (23.0–27.4 kg/m2) and obese (≥27.5 kg/m2) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups. Results Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06–2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17–2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC. Conclusions Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence.