1. Liver disease related to alpha1‐antitrypsin deficiency in French children: The DEFI‐ALPHA cohort.
- Author
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Ruiz, Mathias, Lacaille, Florence, Berthiller, Julien, Joly, Philippe, Dumortier, Jérôme, Aumar, Madeleine, Bridoux‐Henno, Laure, Jacquemin, Emmanuel, Lamireau, Thierry, Broué, Pierre, Rivet, Christine, Belmalih, Abdelouahed, Restier, Lioara, Chapuis‐Cellier, Colette, Bouchecareilh, Marion, Lachaux, Alain, and Tacke, Frank
- Subjects
LIVER diseases ,ALPHA 1-antitrypsin deficiency ,LIVER failure ,PORTAL hypertension ,LIVER transplantation ,CHILDREN - Abstract
Background & Aims: To identify prognostic factors for liver disease in children with alpha‐1 antitrypsin deficiency, irrespective of phenotype, using the DEFI‐ALPHA cohort. Methods: Retrospective, then prospective from 2010, multicentre study including children known to have alpha‐1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model. Results: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow‐up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty‐eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0‐11.6): diagnosis of alpha‐1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIMlikeZ in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007). Conclusion: Alpha‐1 antitrypsin‐deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non‐homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications. See Editorial on Page 1019 [ABSTRACT FROM AUTHOR]
- Published
- 2019
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