Towards a Proposal for a Universal Diagnostic Definition of Protein-Losing Enteropathy in Fontan Patients

Objective: The definition of protein-losing enteropathy (PLE) in Fontan patients is variable and lacks standardization. We sought to 1) determine whether a PLE definition in Fontan is routinely used, and (2) identify useful diagnostic building blocks for composing a uniform PLE definition.

Methods: A systematic search of Medline (PubMed) was performed. PLE definitions were quantitatively analyzed using the so-called ‘building block approach’, in which definitions were fractionated in constituent pieces of diagnostic information.

Results: We identified 363 papers. In the final analysis, data from 55 published articles were extracted. A definition of PLE was used in only 24/55 (43.6%) of the studies. PLE definitions were very heterogeneous. We identified 6 different diagnostic building blocks: (1) hypoalbuminemia (n = 22 studies, 91.7%), (2) hypoproteinemia (n = 9, 37.5%), (3) clinical presentation (n = 17, 70.8%), (4) documentation of enteric protein-loss (n = 14, 58.3%), (5) exclusion of other causes of hypoproteinemia (n = 15, 62.5%), and (6) hypoimmunoglobulinemia (n = 1, 4.2%). Most studies used 3 diagnostic building blocks (range 1–5) to compose a PLE definition (n = 13/24, 54.2%). Cut-off values for laboratory parameters (serum albumin, protein, or fecal α-1-antitrypsin) were frequently incorporated in the PLE definition (n = 15, 62.5%).

Conclusion: Our study emphasizes the need for a uniform and consequent use of a PLE definition in clinical studies concerning Fontan patients. The proposed diagnostic building blocks may help constitute a clinically useful definition.