Skeletal muscle index at the third lumbar vertebra/BMI are positively associated with 1‑year overall survival in male patients with hepatocellular carcinoma treated with immune checkpoint inhibitors

Skeletal muscle loss is a hallmark of malnutrition and a well-established predictor of adverse clinical outcomes. However, its specific role as a risk factor and its prognostic relevance in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) remain incompletely understood. The present study aimed to investigate the relationship between muscle mass (assessed via multiple skeletal muscle indices) and clinical outcomes in male patients with HCC receiving ICIs. A retrospective analysis of 195 male patients with HCC treated with ICIs was performed at Beijing Youan Hospital (Beijing, China). Transverse computed tomography images at the level of the third lumbar vertebra (L3) were analyzed with SliceOmatic software to quantify skeletal muscle parameters. Anthropometric, biochemical and prognostic data were collected and evaluated for association with survival. Among the 195 patients, 161 (82.56%) had hepatitis B virus infection and 163 (83.59%) had cirrhosis. Cumulative mortality at 6, 9 and 12 months was 4, 5 and 15%, respectively. Univariate analysis showed that lower body mass index (BMI) and higher values of L3 skeletal muscle index (L3-SMI), L3-SMI/weight, L3-SMI/height and L3-SMI/BMI were significantly associated with improved 1-year overall survival (OS; P<0.05). In multivariate Cox regression analysis, L3-SMI/BMI remained an independent predictor of 1-year OS (hazard ratio=0.02; 95% CI: 0.001-0.940; P=0.047). SHapley Additive exPlanations analysis further highlighted L3-SMI/BMI as a strong independent predictor for 1-year mortality. The area under the receiver operating characteristic curve of L3-SMI/BMI for predicting 1-year mortality was 0.86 (95% CI: 0.76-0.96), outperforming BMI, L3-SMI, L3-SMI/weight and L3-SMI/height. A higher L3-SMI/BMI ratio was a strong independent predictor of improved 1-year OS in male patients with HCC, predominantly Barcelona Clinic Liver Cancer stage A/B, treated with ICIs. These findings support the potential clinical utility of L3-SMI/BMI as a practical prognostic marker in this patient population.