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  • Title: Fontan protein-losing enteropathy is associated with advanced liver disease and a proinflammatory intestinal and systemic state.
    Author: Rodríguez de Santiago E, Téllez L, Garrido-Lestache Rodríguez-Monte E, Garrido-Gómez E, Aguilera-Castro L, Álvarez-Fuente M, Del Cerro MJ, Albillos A.
    Journal: Liver Int; 2020 Mar; 40(3):638-645. PubMed ID: 31912956.
    Abstract:
    BACKGROUND AND AIMS: Protein-losing enteropathy (PLE) after Fontan surgery carries significant morbimortality. Its pathophysiology and association with other Fontan complications are poorly understood. Our aims were to examine whether Fontan-PLE is associated with greater liver damage and to assess the presence of systemic and intestinal inflammation. METHODS: Fontan patients with PLE and Fontan controls without PLE matched for age and Fontan surgery procedure were included. Data were prospectively compiled on blood and stool tests, liver imaging, elastography, cardiac-MRI and cardiac catheterization. RESULTS: Twenty-nine Fontan patients were enrolled (14 with PLE and 15 controls without PLE). Patients with PLE had more advanced liver disease estimated by non-invasive methods: blunt liver margins on ultrasonography (71.4% vs 26.7%, P = .027), greater median liver stiffness (25.4 vs 14.5 kPa, P = .003) and higher FIB-4 (P = .016). Portal hypertension-related signs were more common in patients with PLE including ascites (P = .035), larger spleen size (P = .005), oesophageal varices/splanchnic collateral shunts (P = .03), higher liver stiffness-spleen size-to-platelet ratio risk score (P < .001) and lower platelet count (P = .01). Systemic proinflammatory cytokines (TNF-α, interleukin-6), biomarkers of intestinal permeability (intestinal fatty-acid binding protein) and faecal calprotectin concentrations were also significantly increased in Fontan-PLE (P < .05). Faecal calprotectin directly correlated with alpha-1 antitrypsin clearance and inversely with cardiac index, total serum proteins and body mass index. CONCLUSION: Fontan-PLE is associated with advanced liver disease and increased markers of systemic inflammation and intestinal permeability. Faecal calprotectin is elevated and correlates with Fontan-PLE severity. Liver assessment is mandatory in all Fontan patients, and especially in those with PLE.
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