Administration

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.

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.

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).

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.