Pre-liver transplant visceral adipose tissue predicts the early development of metabolic syndrome after transplant

Introduction: Post-liver transplantation metabolic syndrome (PTMS) is a significant independent risk factor for cardiovascular disease. Risk factors for developing PTMS include pre-transplant diabetes, obesity, and increasing age.1, 2 Low muscle mass, excess adipose tissue, and poor cardiorespiratory fitness are risk factors for metabolic syndrome in the general population that have not been evaluated in the liver transplant setting.3-5 Our aim was to assess the role of these variables in predicting the early development of PTMS.

Patients and Methods: A retrospective cohort study was performed by assessing consecutive adult patients who received a liver transplant by the Queensland Liver Transplant Service between August 2012 and June 2016 for inclusion. We included 77 patients for analysis. Demographic, anthropometric, and metabolic data were collected before transplantation and at 3 months after transplantation. Metabolic syndrome was defined according to the World Health Organization criteria.6 Pre-transplant computed tomography skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas were measured at the level of the third lumbar vertebrae using ImageJ software (NIH, Bethesda, MD, USA). Cardiopulmonary exercise testing was performed to determine the ventilatory threshold.

Results: The median age was 55 years (IQR, 10; range, 18–67), and 58 patients (75%) were male. Most of the study cohort was Caucasian (n = 72; 94%). The most common cause of liver disease was hepatitis C (57%), followed by primary sclerosing cholangitis (16%) and alcohol (12%). Thirty patients (39%) had a diagnosis of hepatocellular carcinoma.

Ten patients (13%) developed early onset PTMS by 3 months after transplantation. Patients who developed PTMS had a higher body mass index (BMI) (52.4 kg/m2 vs 48.9 kg/m2; P = 0.019), VAT area (182.9 cm2 vs 105.6 cm2; P = 0.001), and SAT area (217.9 cm2 vs 141.6 cm2; P = 0.008). There was no difference in ventilatory threshold (11.4 mL/kg/min vs 11.8 mL/kg/min; P = 0.821) or skeletal muscle index (52.5 cm2/m2 vs 48.9 cm2/m2; P = 0.269) between the two groups.

To evaluate the impact of variables predicting the development of PTMS, univariate and multivariate analyses were performed using logistic regression. Pre-transplant obesity (odds ratio [OR], 6.78; 95% CI, 1.49–30.92; P = 0.13), BMI (OR, 1.23; 95% CI, 1.03–1.48; P = 0.026), VAT (OR, 1.02; 95% CI, 1.01–1.03; P = 0.003), and SAT (OR, 1.01; 95% CI, 1.00–1.02; P = 0.009) were all significant predictors for the development of PTMS on univariate analysis. After multivariate analysis, only VAT remained a significant predictor (OR, 1.02; 95% CI, 1.00–1.04; P = 0.04).

Discussion: VAT is an independent predictor for the early development of PTMS. Body composition analysis using cross-sectional imaging before liver transplantation can provide additional information to risk-stratify patients for PTMS. These patients have a high risk for cardiovascular disease and could be targeted for intervention, either before or early after liver transplantation.