Visceral-to-subcutaneous fat ratio is a time-stable predictor of survival and toxicity in advanced hepatocellular carcinoma

Abstract

Abstract Purpose Nutritional status significantly impacts the prognosis of patients with hepatocellular carcinoma (HCC). Computed tomography (CT) has become a key tool for assessing body composition (BC), with abnormal patterns increasingly linked to reduced survival. However, BC is dynamic and may change during treatment, potentially affecting treatment outcomes. This study explores how BC affects survival and dose-limiting toxicities (DLTs) in patients with advanced HCC receiving first-line treatment, as well as changes in BC over the course of treatment. Methods This retrospective study included patients with advanced HCC who received first-line systemic therapy. The Lumbar skeletal muscle index and adipose tissue indices were measured via CT analysis at baseline and at the best response. Cox regression and generalized linear models were used for analysis. Results The study included 113 patients treated with tyrosine kinase inhibitors (70%) or immune checkpoint inhibitors (30%), primarily atezolizumab and bevacizumab. Univariable analyses identified a high visceral-to-subcutaneous adipose tissue ratio (VSR) and muscle depletion as predictors of poor survival. The association between elevated VSR and reduced survival was further confirmed in bivariable models adjusted for relevant prognostic factors. Elevated VSR was also associated with an increased incidence of DLT (hazard ratio [HR]: 1.16, 95% CI: 1.08–1.26, p < 0.001). Although most patients experienced muscle and fat loss during treatment, VSR remained stable. At the time of best radiologic response, high VSR remained associated with poorer survival outcomes (HRs for progression-free survival and overall survival: 1.37 and 1.12, respectively; p < 0.001). Conclusions Although validation in larger studies is needed, our study suggests that VSR is a robust, time-stable predictor of survival and toxicity in patients with advanced HCC.