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Introduction <p>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.</p> Methods <p>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 (<i>n</i> = 112) was followed for a mean of 3.8 years to identify predictors of liver nodule development.</p> Results <p>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.</p> Conclusions <p>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.</p>

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

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  • 发表日期：

    2026年4月8日

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  • Takuma Nakatsuka,
  • Tamaki Kobayashi,
  • Ryosuke Tateishi,
  • Yui Ozawa,
  • Katsura Soma,
  • Hiroyuki Tokiwa,
  • Akihito Saito,
  • Takuma Kaneko,
  • Keisuke Mabuchi,
  • Yuki Matsushita,
  • Tomoharu Yamada,
  • Kazuya Okushin,
  • Tatsuya Minami,
  • Masaya Sato,
  • Yotaro Kudo,
  • Momoe Endo,
  • Yuki Ikeda,
  • Makiko Kurihara,
  • Mamiko Sato,
  • Hiroaki Gotoh,
  • Tomomi Iwai,
  • Takayuki Tsujimoto,
  • Akihiko Fukagawa,
  • Tetsuo Ushiku,
  • Makoto Kurano,
  • Ryo Inuzuka,
  • Mitsuhiro Fujishiro

摘要

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.