Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Liver International Année : 2019

Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort

Résumé

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, PIMlike Z 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.
Fichier non déposé

Dates et versions

hal-02195200 , version 1 (26-07-2019)

Identifiants

Citer

M. Ruiz, F. Lacaille, J. Berthiller, P. Joly, J. Dumortier, et al.. Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort. Liver International, 2019, 39 (6), pp.1136--1146. ⟨10.1111/liv.14035⟩. ⟨hal-02195200⟩
77 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More