GLIM-defined malnutrition and cachexia are associated with overall survival in patients with hepatocellular carcinoma...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and prognosis in advanced stages remains poor despite systemic therapy. Malnutrition is common in HCC due to the combined impact of cancer and chronic liver disease and is associated with worse clinical outcomes. However, the prognostic relevance of malnutrition and cachexia defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients treated with sorafenib remains poorly established.

This retrospective single-center cohort study included adult patients with HCC treated with sorafenib between 2010 and 2018. Clinical, laboratory, and imaging data were extracted from electronic medical records. Body composition was assessed on CT images at the L3 level using an automated segmentation algorithm. Malnutrition was defined according to GLIM criteria (≥1 phenotypic and ≥1 etiologic criterion), and cachexia was defined as the coexistence of phenotypic criteria and systemic inflammation (NLR ≥2.3). The primary outcome was overall survival, analyzed using Kaplan-Meier curves and Cox proportional hazards models. All 21 possible GLIM criteria combinations were explored using univariable and multivariable Cox models, with correction for multiple testing using the Benjamini-Hochberg procedure.

A total of 99 patients were included. GLIM-defined malnutrition was present in 51.5% and cachexia in 37.4%. Malnourished patients were older and had shorter duration of sorafenib therapy. They also exhibited greater weight loss, lower skeletal muscle index, reduced muscle radiodensity, and higher inflammatory burden (all p < 0.05). Cachectic patients showed significantly lower muscle mass, higher prevalence of low muscularity, and elevated NLR. During follow-up (93 deaths), cachexia (HR 1.67, 95% CI 1.09-2.55) and inflammation (HR 1.93, 95% CI 1.28-2.93) were associated with worse survival in univariable analysis. In multivariable models, both malnutrition (HR 1.60, 95% CI 1.00-2.54) and cachexia (HR 1.63, 95% CI 1.03-2.60) were independently associated with shorter overall survival. Exploratory analyses corrected for multiple testing showed the strongest associations for combinations integrating weight loss, low muscularity, and inflammation.

GLIM-defined malnutrition and cachexia were independently associated with shorter overall survival in patients with hepatocellular carcinoma treated with sorafenib. These findings suggest that integrating nutritional, body-composition, and inflammatory parameters may provide clinically relevant prognostic information in this population.