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Semin Liver Dis 2023; 43(03): 258-266
DOI: 10.1055/a-2122-7674
Review Article

Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency

Mathias Ruiz
1   Hépatologie, Gastroentérologie et Nutrition Pédiatriques, Hôpital Femme Mère Enfant, Hospices civils de Lyon, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Lyon, France
,
Florence Lacaille
2   Service de Gastroentérologie-Nutrition Pédiatriques et Unité d'Hépatologie Pédiatrique Hôpital Universitaire Necker-Enfants Malades, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Paris, France
,
Christina Schrader
3   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
,
Monica Pons
4   Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Barcelona, Spain
5   Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
,
Piotr Socha
6   The Children's Memorial Health Institute, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Al. Dzieci Polskich, Warszawa, Poland
,
Aleksander Krag
7   Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
,
Ekkehard Sturm
8   Pediatric Gastroenterology and Hepatology, University Children's Hospital Tübingen, Member Center of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Tübingen, Germany
,
Marion Bouchecareilh
9   University of Bordeaux, CNRS, INSERM, BRIC, U1312, Bordeaux, France
,
Pavel Strnad
3   Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany
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Funding None.
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Abstract

Alpha-1 antitrypsin deficiency (AATD) arises due to inherited variants in SERPINA1, the AAT gene that impairs the production or secretion of this hepatocellular protein and leads to a gain-of-function liver proteotoxicity. Homozygous Pi*Z pathogenic variant (Pi*ZZ genotype) is the leading cause of severe AATD. It manifests in 2 to 10% of carriers as neonatal cholestasis and 20 to 35% of adults as significant liver fibrosis. Both children and adults may develop an end-stage liver disease requiring liver transplantation. Heterozygous Pi*Z pathogenic variant (Pi*MZ genotype) constitutes an established disease modifier. Our review summarizes the natural history and management of subjects with both pediatric and adult AATD-associated liver disease. Current findings from a phase 2 clinical trial indicate that RNA silencing may constitute a viable therapeutic approach for adult AATD. In conclusion, AATD is an increasingly appreciated pediatric and adult liver disorder that is becoming an attractive target for modern pharmacologic strategies.

Keywords

cirrhosis - hepatitis - children


Publication History

Accepted Manuscript online:
04 July 2023

Article published online:
09 August 2023

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