Fontan-Associated Liver Disease: Predictors of Elevated Liver Stiffness and the Role of Transient Elastography in Long-Term Follow-Up.

AIM: Fontan-associated liver disease (FALD) is common after the Fontan procedure; however, no established non-invasive screening method exists. We aimed to evaluate the utility of transient elastography (TE) for FALD and identify clinical predictors of increased liver stiffness in post-Fontan patients.

METHODS

This was a single-center retrospective study of 37 adult patients (≥18 years) who had undergone Fontan procedure and received TE during routine follow-up between February 2019 and June 2024 at Kagoshima University Hospital in Kagoshima, Japan. Clinical, laboratory, cardiac, and abdominal ultrasound data were collected. TE using Fibroscan® was performed by a trained clinician. Reliability criteria included 10 validated measurements and an interquartile range/median of less than 0.3 of the obtained liver stiffness measurements (LSMs). Univariate and multivariate linear regression analyses were performed to identify independent predictors of elevated liver stiffness. Since no validated cut-off values for LSM have been established, LSM was treated as a continuous variable, and exploratory analyses were conducted.

RESULTS

The median age was 27 (19-38) years, with 68% men. The median age at Fontan procedure was four years, and the median duration since Fontan procedure (Fontan duration) was 23 (16-31) years. The median LSM was 13.6 kPa (range: 6.5-38.8), indicating advanced fibrosis or liver cirrhosis. In the univariate analysis, age (B = 0.491, 95% CI: 0.096-0.887, p = 0.016), age at Fontan procedure (B = 1.276, 95% CI: 0.251-2.300, p = 0.016), body mass index (B = 0.833, 95% CI: 0.167-1.499, p = 0.016), B-type natriuretic peptide (BNP) (B = 0.114, 95% CI: 0.002-0.227, p = 0.045), gamma-glutamyl transferase (GGT) (B = 0.042, 95% CI: 0.001-0.083, p = 0.046), fibrosis-4 (FIB-4) index (B = 7.746, 95% CI: 3.212-12.280, p < 0.001), AST-to-platelet ratio index (APRI) (B = 12.873, 95% CI: 4.107-21.639, p = 0.005), systematic ventricular morphology (B = 4.351, 95% CI: 0.747-7.954, p = 0.019), and spleen index (B = 0.363, 95% CI: 0.024-0.702, p = 0.037) were significantly associated with LSM. Variables without missing data were prioritized for inclusion in the multivariate analysis. GGT and BNP were included in the multivariate model as potential confounders, given their established association with both liver congestion. In addition, since FIB-4 had a lower p-value than APRI in the univariate analysis and is considered a more clinically relevant fibrosis marker, it was included in the multivariate analysis. In the multiple regression analysis, the FIB-4 index (B = 6.246, 95% CI: 1.735-10.757, p = 0.008), GGT (B = 0.043, 95% CI: 0.003-0.082, p = 0.034), and age at Fontan procedure (B = 1.141, 95% CI: 0.185-2.097, p = 0.021) were all independently associated with higher LSM.

CONCLUSION

In adult patients who had undergone a Fontan procedure, factors such as the FIB-4 index, GGT, and age at Fontan procedure were associated with elevated LSM. These findings suggest that TE may be a useful tool for early detection of hepatic fibrosis in high-risk patients, although further studies are needed to confirm these results.