## 4 Discussion
### Biochemical Markers  
In several studies, standard hepatic laboratory parameters (liver enzymes, bilirubin, alkaline phosphatase, prothrombin time) showed no correlation to fibrosis detected on biopsy in patients with congestive hepatopathy [4]. AST and ALT are rarely elevated in stable Fontan patients and are not adequate for identifying and determining the severity of Fontan-associated liver disease [4]. Other studies showed that the most frequently altered standard laboratory test in Fontan patients is GGT, as a marker of stasis [41; 42]. We found statistically significant differences for Fontan patients compared to controls for GGT and ALT. The GGT levels were also significantly higher in the Fontan group compared to the Glenn group. AST and ALT levels were significantly increased in the Glenn group compared to controls. Further, when comparing the operated patients ([PERSON] + Glenn groups) to the control group, we found statistically increased levels for AST, ALT and GGT. Several studies have shown that a decreased platelet count correlates significantly to the degree of liver fibrosis in several hepatic disorders [43], whereas in congestive liver disease, a low platelet count is possibly secondary to splenic sequestration due to portal hypertension [44]. In our study, the platelet count was significantly lower in Fontan patients versus controls as well as in operated patients ([PERSON] + [PERSON]) versus controls. Fibrotest/Actitest was extensively studied and validated with biopsy in Hepatitis B and C patients. However, there is less data on the modifications of this parameter in congestive hepatopathy. In a study on 145 patients with Fontan operation, Fibrotest showed a strong correlation to the period of time after the Fontan surgery and a mild correlation with liver stiffness values [41], whereas other studies failed to obtain a correlation between the duration of the Fontan circuit and Fibrotest [45]. In Fontan patients, we demonstrated statistically significant differences for Fibrotest and Actitest compared to the control group. In addition, Fibrotest, and Actitest levels were significantly increased both in Glenn patients and in the operated patients ([PERSON] and [PERSON]) versus controls. We also found a positive correlation between the time after the Glenn operation and Fibrotest scores. The serum fibrosis markers were more elevated in older patients with Glenn surgery who did not undergo the Fontan surgery for different reasons. This indicates that hypoxia and precarious hemodynamics specific to the Glenn patients affect the liver, thus liver damage starts before the Fontan surgery. We have also obtained a positive correlation between Actitest and liver stiffness results, both in the Fontan and the Glenn group. This could infer that necro-inflammatory activity may increase the results of liver stiffness. Elastographic measurements are known to be altered secondary to increased ALT values [44], but it is important to state that although the ALT levels were increased in Fontan and Glenn patients compared to controls, the values were in the normal range for age. In Fontan patients, Actitest and ALT results correlated with the time after the operation, thus the liver inflammation tends to increase over time. With regards to the components of the Fibrotest, we have found that ApoA1 is significantly decreased in both Fontan and Glenn patients and also the total of operated patients (Fontan + Glenn) compared to controls. A significantly decreased level of haptoglobin was observed in the operated patients compared to controls. We obtained increased levels of A2 MG in Fontan and Glenn patients but without statistical significance. These results are in line with the studies showing decreased levels of ApoA1 and haptoglobin and increased A2 MG correlating with increased liver fibrosis [46]. APRI and FIB-4 scores have been studied as non-invasive fibrosis markers in several liver diseases [47].