Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis

Abstract

Background & aims: Two major body compartments, skeletal muscle and adipose tissue, exhibit independent functions. We aimed to explore the prognostic significance of skeletal muscle, visceral and subcutaneous adipose tissue, according to sex, in patients with cirrhosis assessed for liver transplantation (LT).

Methods: CT images taken at the 3rd lumbar vertebra from 677 patients were quantified for three body composition indexes (cm²/m²), visceral adipose tissue index, subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI). Cox proportional and competing-risk analysis hazard models were conducted to assess associations between mortality and body composition.

Results: The majority of patients were male (67%) with a mean age of 57 ± 7 years, model for end-stage liver disease (MELD) score of 14 ± 8 and mean body mass index of 27 ± 6 kg/m². Despite similar body mass index between the sexes, male patients had greater SMI (53 ± 12 vs. 45 ± 9 cm²/m²), whereas SATI (67 ± 52 vs. 48 ± 37 cm²/m²) was higher in females (p <0.001 for each). In sex stratified multivariate analyses after adjustment for MELD score and other confounding variables, SATI in females (hazard ratio [HR] 0.99; 95% CI 0.98-1.00; p = 0.01) and SMI in males (HR 0.98; 95% CI 0.96-1.00; p = 0.02) were significant predictors of mortality. Female patients with low SATI (<60 cm²/m²) had a higher risk of mortality (HR 2.06; 95% CI 1.08-3.91; p = 0.03). Using competitive risk analysis in female patients listed for LT, low SATI was also an independent predictor of mortality (subdistribution HR 2.80; 95% CI 1.28-6.12; p = 0.01) after adjusting for MELD, and other confounding factors.

Conclusions: A lower SATI is associated with higher mortality in female patients with cirrhosis. Subcutaneous adipose tissue has a favorable metabolic profile - low SATI may reflect depletion of this major energy reservoir, leading to poor clinical outcomes.

Lay summary: We looked at the importance of two of the main body compartments, skeletal muscle and adipose tissue (fat) on the prognosis of males and females with end-stage liver disease. Lower amounts of subcutaneous fat but not visceral fat (around internal organs), are associated with higher mortality in female patients with end-stage liver disease. However, low skeletal muscle predicts mortality in male patients with end-stage liver disease.

Keywords: Adipose tissue; Body composition; Computed tomography; End-stage liver disease; Survival.