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.
Liver Int. 2020 Jan 8. doi: 10.1111/liv.14375. [Epub ahead of print]
PMID: 31912956
Take Home Points:
- Fontan patients with PLE demonstrated more severe liver damage and cardiac impairment, and greater systemic inflammation, intestinal inflammation and intestinal permeability than those without PLE.
- Timely reminder that liver assessment and close surveillance is essential in all Fontan patients, and especially those with PLE.
- Faecal calprotectin is complementary to faecal alpha-1-antitrypsin and may be useful as a biomarker for the diagnosis and follow-up of Fontan PLE.
- Data originates from an observational single-centre case-control study (n=29).
Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:
Background
Protein-losing enteropathy (PLE) affects 3 – 18 % of patients after a Fontan operation, and is thought to be contributed by factors including elevated central venous pressure and inflammation.
Aims of this study: to investigate in patients with Fontan circulation and PLE:
a. the presence of intestinal and systemic inflammation;
b. the relationship between PLE and severity of liver and cardiac damage.
Methods
All Fontan subjects diagnosed prospectively with PLE were included. PLE was defined as a 24 hours alpha-1-antitrypsin faecal clearance value above 27 mL/day. Exclusion criteria were coexisting inflammatory bowel disease, coeliac disease or gastrointestinal infection. Controls were matched at a 1:1 ratio by age (±2 years) and Fontan surgery procedure (atriopulmonary vs total cavopulmonary).
Initial assessment included a structured medical interview, physical examination, blood and faeces tests, abdominal Doppler-ultrasonography, liver elastography, abdominal angio-magnetic resonance imaging (MRI) or computed tomography (CT) scan when MRI was contraindicated, and echocardiography. A cardiac MRI and cardiac haemodynamic study were also performed when clinically indicated.
Results
Of 61 subjects, 15 had PLE (24.6 %) with one excluded following diagnosis of coeliac disease. Fifteen control Fontan patients were included (see Figure 1, below).
Faecal calprotectin was significantly increased in the PLE group (80 vs 30 ug/g, P < 0.001; Figure 2). Serum I-FABP, used as a marker of intestinal barrier disruption, was elevated in PLE (9 vs 5 ng/ml, P = 0.019), while pro-inflammatory cytokines TNF-alpha and IL-6 were also elevated in the PLE cohort (Figure 3).
Cardiac index was lower in PLE subjects in the hemodynamic study (2.54 vs 4.25 L/min/m2, P = .016), lower ventricular ejection fraction on cardiac MRI (58.5% vs 63.5%, P = .04) and lower systemic oxygen saturation (93% vs 96%, P = .025). No difference in BNP was observed.
No difference in routine liver function testing was observed (bilirubin, ALT, AST, GGT, ALP). Platelet count was lower, while liver stiffness was greater (25.4 vs 14.3 kPA; P < 0.001) in the PLE group. No cases of hepatocarcinoma were diagnosed.
Conclusions
Fontan patients with PLE demonstrated more severe liver damage and cardiac impairment, and greater systemic inflammation, intestinal inflammation and intestinal permeability than those without PLE.
Faecal calprotectin is complementary to faecal alpha-1-antitrypsin and may be useful as a biomarker for the diagnosis and follow-up of Fontan patients diagnosed with PLE.
