Heterogeneous associations of regional adipose depots with liver fibrosis in U.S. adults

Liver fibrosis is the key determinant of prognosis in metabolic dysfunction–associated steatotic liver disease (MASLD). While obesity is a major risk factor, whether regional adipose tissue distribution differentially relates to fibrosis independent of overall adiposity remains unclear. We analyzed data from 3,668 U.S. adults participating in NHANES 2017–2018 with available dual-energy X-ray absorptiometry and vibration-controlled transient elastography. Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and thigh subcutaneous adipose tissue (tSAT) were expressed as percentages of total fat mass (VAT%, aSAT% and tSAT%). Clinically significant fibrosis was defined as liver stiffness measurement >8.0 kPa. Survey-weighted logistic regression models were used with sequential adjustment for demographic factors, lifestyle factors, and body mass index (BMI). Clinically significant fibrosis was present in 9.7% of participants. Higher tSAT% was consistently associated with lower odds of fibrosis across all models. In the fully adjusted model, each 1% increase in tSAT% was associated with lower odds of fibrosis (odds ratio 0.91, 95% confidence interval 0.84–0.99). In contrast, VAT% was not independently associated with fibrosis. The association between aSAT% and fibrosis was not significant after multivariable adjustment. Regional fat distribution exhibits heterogeneous associations with liver fibrosis. Thigh subcutaneous fat shows an inverse association with fibrosis that persists after adjustment for overall adiposity (BMI), whereas abdominal fat depots do not. These findings highlight fat distribution as a clinically relevant dimension beyond total adiposity for refining fibrosis risk stratification in MASLD.