Noninvasive risk stratification of liver nodule development in Fontan-associated liver disease using liver stiffness measurement

Abstract Introduction Fontan-associated liver disease (FALD) is a progressive congestive hepatopathy that often leads to cirrhosis and hepatocellular carcinoma. Liver nodules are common in FALD; however, noninvasive predictors remain understudied. This study aimed to determine the prevalence and risk factors for liver nodule development in patients with Fontan circulation. Methods This prospective single-center cohort study enrolled 198 post-Fontan patients (median age 17.3 years; median time since Fontan surgery 14.0 years) who underwent abdominal ultrasound and liver stiffness measurement (LSM) by transient elastography between January 2015 and June 2025. Cross-sectional analysis assessed baseline predictors of liver nodules. A longitudinal subset ( n = 112) was followed for a mean of 3.8 years to identify predictors of liver nodule development. Results Abnormal ultrasonographic findings were detected in 90% of patients, with a higher frequency in those ≥ 10 years post-Fontan. Liver nodules (≥ 1 cm) were present at baseline in 8.6% of patients. In cross-sectional multivariable analysis, only LSM remained significantly associated with liver nodules (adjusted odds ratio per 1 kPa: 1.06, 95% confidence interval CI 1.01–1.12). During longitudinal follow-up, 10 patients developed liver nodules. Higher LSM (adjusted hazard ratio per 1 kPa: 1.10, 95% CI 1.02–1.18) and heterotaxy (adjusted hazard ratio: 9.21, 95% CI 2.50–33.97) independently predicted liver nodule development. Restricted cubic spline analysis demonstrated a monotonic increase in liver nodule risk with increasing LSM. Conclusions This is the first prospective study demonstrating that elevated LSM predicts liver nodule development after Fontan surgery. LSM represents a practical, noninvasive tool for risk stratification in FALD.