{Author 1 (Prefix):11.2} {Author 1 (Last):11.6}

TitelCholestasis is associated with impaired hepatic synthetic function in Children, Adolescents and Adults with Fontan Circulation
Einleitung

Fontan associated liver disease (FALD) is a hepatic disorder arising from hemodynamic changes following Fontan surgery. FALD-induced hepatic fibrosis is rarely marked by biochemical alterations, however, a chronic increase in serum bile acid (BA) levels has been observed in some patients indicating cholestasis. We investigated clinical -, hemodynamic- and biochemical variables in Fontan patients with and without cholestasis.

Patient/en und Methoden

We investigated common biochemical markers and serum human BA, measured by mass spectrometry, in 45 patients (pediatrics n=18, adults n=27) who underwent Fontan surgery. Using a cutoff value of ≥10 µg/ml BA in serum, two groups of Fontan patients could be distinguished (cholestatic n=6, non-cholestatic n=39). Anticoagulation therapy was used as follows: Thrombo ASS was taken by in 18 patients (cholestatic n=0, non-cholestatic n=18) and Phenprocoumon (PhC) by in 20 patients (cholestatic n=4, non-cholestatic n=16) with comparable dosages within the respective study groups.

Ergebnisse

Cholestatic Fontan patients showed significantly increased total bilirubin- (median: 1,4mg/dl; interquartile range [IQR]: 0,6-3,6mg/d) and NTproBNP level (median: 111 pg/ml, IQR: 170,1-523,5 pg/ml) compared to non-cholestatic patients (bilirubin median: 0,8mg/dl, IQR]: 0,6-1,0mg/dl, p=0,007; NTproBNP median: 119 pg/ml, IQR: 79,6-230,9 pg/ml, p=0,032). Moreover, Fontan patients with cholestasis had a significantly decreased platelet count (median: 133.000/µl, IQR: 159.450-280.330/µl) and antithrombin III (ATIII) levels (median: 82%, IQR: 66,3-102,9%) compared to non-cholestatic patients (platelet median: 196.000/µl, IQR: 46.000-.324.900/µl, p=0,023; ATIII median: 101% IQR: 95,9-104,6%, p= 0,002). In all Fontan patients on PhC therapy, INR (international normalized ratio) and aPTT (partial thromboplastin time) values were significantly increased in cholestatic Fontan patients (INR: median 2,9, IQR: 2,3-3,3; aPTT median: 54 sec, IQR: 38,8-70,1 sec) compared to non-cholestatic patients on PhC (INR: median 2,1, IQR: 1,6-2,3, p=0,011; aPTT median: 46 sec, IQR: 36,9-63,1 sec, p=0,036).

Schlussfolgerung/Diskussion

Cholestasis in Fontan patients is associated with lower platelet count and ATIII levels and with enhanced INR and aPTT values. Our findings argue for an impaired hepatic synthetic function in cholestatic patients with Fontan circulation. However, those findings need further investigation by a larger study cohort.

Autor*in 1Katharina Meinel Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 2Martin Dusleag Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 3Martin Koestenberger Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 4Daniela Baumgartner Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 5Nathalie Noessler Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 6Stefan Kurath-Koller Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 7Gernot Grangl Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 8Ante Burmas Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology
Autor*in 9Sandra Gasser Department of Internal Medicine, Division of Cardiology, Medical University of Graz,
Autor*in 10Felicitas Korak Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, Medical University of Graz,
Autor*in 11Axel Schlagenhauf Department of Pediatrics and Adolescent Medicine, Division of General Pediatrics, Medical University of Graz,
Autor*in 12Andreas Gamillscheg Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology