Noninvasive Risk Stratification of Liver Nodule Development in Fontan-Associated Liver Disease Using Liver Stiffness Measurement

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, non-invasive predictors are poorly defined. We aimed to determine the prevalence and risk factors for liver nodule development in post-Fontan patients. METHODS: This prospective single-center cohort study enrolled 201 post-Fontan patients (median age 17.4 years; median time since Fontan surgery 14.1 years) who underwent abdominal ultrasound and liver stiffness measurement (LSM) by transient elastography. Cross-sectional analysis assessed baseline predictors of liver nodules. A longitudinal subset (N=115) was followed for a mean of 3.9 years to identify predictors of the development of liver nodule. RESULTS: Abnormal ultrasonographic findings were detected in approximately 90% of patients, with higher frequency in those ≥10 years post-Fontan. Liver nodules (≥1 cm) were present at baseline in 8.5% of patients. In cross-sectional multivariate 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 2.50–33.53) independently predicted liver nodule development. Restricted cubic spline analysis demonstrated a monotonic increase in liver nodule risk with increasing LSM. DISCUSSION: This is the first prospective study demonstrating that elevated LSM predicts liver nodule development after Fontan surgery. LSM represents a practical, noninvasive tool for early risk stratification in FALD.