Liver stiffness measured by MR elastography in children and adults with Fontan circulation: defining expected values and clinical associations

Background MRI is increasingly used to assess Fontan-associated liver disease (FALD), but the expected range and variability of MR elastography (MRE) shear stiffness measurements as well as their clinical associations remain poorly understood. Objective This study aimed to define the range of MR elastography (MRE) measured liver shear stiffness and its clinical associations in a large pediatric and adult cohort of patients post-Fontan. Materials and methods This retrospective cross-sectional study included children and adults who underwent baseline clinical liver MRE between February 2013 and June 2024. Mean liver stiffness (kPa) and liver volume (mL) were obtained from clinical reports, while spleen length was measured on coronal T2-weighted images. Clinical data, Fontan conduit size, Fontan pathway pressure, fenestration status, and presence of protein-losing enteropathy were collected within 6 months of imaging. Associations between liver stiffness and clinical variables were assessed using Pearson correlation and multiple linear regression. Clinical characteristics were compared between patients in the lowest (≤ 20th) and highest (≥ 80th) percentiles of liver stiffness. Results Our study sample included 206 Fontan patients (mean age 19.7 years; 114 male). Mean liver stiffness was 4.4 ± 1.0 kPa (range 2.1–7.4 kPa). Liver stiffness was associated with aspartate aminotransferase (AST) ( r =0.23, P =0.003), total bilirubin ( r =0.31, P <0.0001), and male sex (4.6 vs. 4.1 kPa; P =0.0002), but not with liver volume ( r =0.06, P =0.39) or spleen length ( r =0.08, P =0.25). In a regression model excluding Fontan conduit size and Fontan pressure ( n =143), male sex ( P = 0.02), total bilirubin ( P =0.003), and AST ( P = 0.048) were independent predictors of liver stiffness ( R 2 =0.16). In a smaller cohort with available conduit size and pressure data ( n =32), predictors of liver stiffness were AST ( P =0.002), ALT ( P =0.03), Fontan pressure ( P =0.0004), and male sex ( P = 0.03) ( R 2 = 0.59). Patients with ≥ 80th percentile liver stiffness were more likely to be male ( P =0.004), had a lower BMI (23.2 vs. 26.3 kg/m 2 , P =0.04), and had a higher total bilirubin (1.4 vs. 0.8 mg/dL, P =0.01) compared to those with ≤ 20th percentile liver stiffness. Conclusion MRE liver stiffness is elevated and highly variable in individuals with Fontan circulation, with higher measurements associated with male sex, liver-related laboratory changes, and Fontan pathway pressure.