Protein-losing enteropathy after Fontan operation: Investigations into possible pathophysiologic mechanisms

Background. Protein-losing enteropathy (PLE) is an enigmatic disease with significant morbidity and mortality seen after the Fontan operation. The pathophysiology is poorly understood. The purpose of this study is to investigate the association between PLE after the Fontan operation and candidate pathophysiologic mechanisms of the disease by searching for abnormalities of the following: (1) mesenteric blood flow; (2) systemic inflammation; (3) neurohormonal activation; (4) protein glycosylation. Methods. A cross-sectional analysis of 62 patients after the Fontan operation was performed. Twenty-four hour stool sample was collected for alpha-1-antitrypsin (A1AT) clearance, to determine the presence of abnormal enteric protein loss (AEPL) defined as either an abnormal fecal A1AT clearance of greater than 27 mL/24 hours, or an abnormal fecal A1AT concentration of greater than 54 mg/dL. Subjects underwent ultrasonography of the mesenteric and celiac artery blood flow and blood draw for tumor necrosis factor-alpha (TNF-a), high sensitivity C reactive protein (CRP), brain natriuretic peptide (BNP), angiotensin II, coagulation factors protein S, protein C, and antithrombin III (AT III), and serum transferrin for determination of glycosylation defect. Results. Age at study was 10.9 +/- 3.4 years; 8.6 +/- 3.9 years after the Fontan operation. Seven subjects had AEPL. Mesenteric-to-celiac artery flow ratio was lower for the AEPL group, than for the non-AEPL group (p < 0.05). The TNF-a, CRP, BNP, and angiotensin II levels were elevated; however, there was no correlation with AEPL. Abnormalities in coagulation factors were present but did not correlate with AEPL. No glycosylation defects were identified. Conclusions. Potential candidate mechanisms for elucidation of the pathophysiology of PLE include abnormal mesenteric vascular resistance and inflammation, conditions uniquely present after the Fontan operation. Targeted investigations of these parameters may provide clues as to the mechanism of onset of PLE after Fontan operation.