Fontan-Associated Liver Disease—Higher Prevalence with Increasing Age

Introduction: Liver fibrosis is increasingly recognized as a potentially serious morbidity associated with Fontan circulation (Fontan-associated liver disease [FALD]). The purpose of this study was to assess the prevalence of liver abnormalities in different age groups.

Methods: Fontan patients were screened for liver abnormalities by abdominal ultrasound and routine laboratory tests. Patients were divided into three groups based on follow-up since Fontan surgery (<5, 5–10, and >10 years). Laboratory tests were interpreted based on age and gender-adjusted reference values.

Results: A total of 273 Fontan patients seen for routine follow-up between March 2013 and August 2018 were included. Abdominal ultrasound was performed in 189 patients, and routine laboratory tests were obtained in all patients. Median age at follow-up was 11 (interquartile range [IQR] 7–16) years, and the follow-up since Fontan surgery was 8 (IQR 4–13) years. Sonographic signs of fibrotic changes included heterogeneous parenchyma, surface nodularity, or hyperechoic lesions in 91 (48%) patients. The prevalence of fibrotic changes increased with longer duration of follow-up (< 5 years: 9/39 [23%]; 5–10 years: 25/55 [45%]; >10 years: 57/95 [60%]; p < 0.001).

Elevated gamma-glutamyltranspeptidase (GGT) levels were common in all groups, but less frequent with more than 10 years of follow-up (< 5 years: 84%; 5–10 years: 96%; >10 years: 67%; p < 0.001). Glutamic–oxaloacetic–transaminase (GOT) levels above normal range were more common with more than 10 years of follow-up (17 vs. 28%, p < 0.033). Thrombocytopenia, a feature of portal hypertension, was observed in 5 and 4% of cases with less than 5 and 5 to 10 years of follow-up, but in 29% with more than 10 years of follow-up (p < 0.001). Hypoalbuminemia was also more common with more than 10 years of follow-up (3 vs. 11%, p = 0.012). Reduced prothrombin activity was found in 28% of cases without oral anticoagulation with no difference between age groups (p = 0.289).

Mean GGT levels were higher in patients with sonographic signs of fibrosis (67 ± 47 vs. 49 ± 30 U/L, p = 0.001), while absolute values of other laboratory data showed no differences. The frequency of hypoalbuminemia was higher in cases with suspected fibrosis (11 vs. 2%, p = 0.027).

Conclusion: The prevalence of ultrasound and laboratory abnormalities suggestive of FALD increases with time since Fontan surgery, but ultrasound abnormalities were not necessarily reflected by laboratory abnormalities and vice versa.