Alpha1-antitrypsin deficiency: An updated review.

Jean-François Mornex, Julie Traclet, Olivier Guillaud, Magali Dechomet, Christine Lombard, Mathias Ruiz, Didier Revel, Philippe Reix, Vincent Cottin

Journal: Presse medicale (Paris, France : 1983) 2024;52(3):104170

PMID: 37517655

Full Text on Elsevier Science View on PubMed

Abstract

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking. Liver fibrosis is due to the ZZ homozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1 gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients.

Address: Université de Lyon, université Lyon 1, INRAE, EPHE, UMR754, IVPC, F-69007 Lyon, France; Centre de référence des maladies pulmonaires rares, Orphalung, RESPIFIL, ERN-LUNG, F-69500 Bron, France; Hospices civils de Lyon, hôpital Louis-Pradel, service de pneumologie, F-69500 Bron, France; Inserm, hospices civils de Lyon, CIC 1407, F-69500 Bron, France. Electronic address: [email protected].; Centre de référence des maladies pulmonaires rares, Orphalung, RESPIFIL, ERN-LUNG, F-69500 Bron, France; Hospices civils de Lyon, hôpital Louis-Pradel, service de pneumologie, F-69500 Bron, France.; Ramsay générale de santé, clinique de la Sauvegarde, F-69009 Lyon, France; Hospices civils de Lyon, hôpital Edouard Herriot, Fédération des spécialités digestives, F-69003 Lyon, France.; Hospices civils de Lyon, hôpital Lyon sud, service d'immunologie biologique, F-69495 Pierre Bénite, France.; Centre de référence de l'atrésie des voies biliaires et des cholestases génétiques, FILFOIE, F-69500 Bron, France; Hospices civils de Lyon, hôpital femme mère enfant, service d'hépatologie, gastroentérologie et nutrition pédiatrique, F-69500 Bron, France.; Hospices civils de Lyon, hôpital Louis Pradel, service d'imagerie, F-69500 Bron, France.; Service de pneumologie, allergologie pédiatrique. Hôpital Femme Mère Enfant. Hospices civils de Lyon, F-69500 Bron, France; Université de Lyon, université Lyon, CNRS, UMR 5558, équipe EMET, F-69100 Villeurbanne, France.; Université de Lyon, université Lyon 1, INRAE, EPHE, UMR754, IVPC, F-69007 Lyon, France; Centre de référence des maladies pulmonaires rares, Orphalung, RESPIFIL, ERN-LUNG, F-69500 Bron, France; Hospices civils de Lyon, hôpital Louis-Pradel, service de pneumologie, F-69500 Bron, France.

DOI: 10.1016/j.lpm.2023.104170