Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency

Mathias Ruiz; Florence Lacaille; Christina Schrader; Monica Pons; Piotr Socha; Aleksander Krag; Ekkehard Sturm; Marion Bouchecareilh; Pavel Strnad

doi:10.1055/a-2122-7674

Seminars in Liver Disease, Table of Contents

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

¹Hépatologie, 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

²Service 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

³Medical 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

⁴Liver 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

⁵Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain

,

Piotr Socha

⁶The Children's Memorial Health Institute, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Al. Dzieci Polskich, Warszawa, Poland

,

Aleksander Krag

⁷Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

,

Ekkehard Sturm

⁸Pediatric 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

⁹University of Bordeaux, CNRS, INSERM, BRIC, U1312, Bordeaux, France

,

Pavel Strnad

³Medical 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

› Author Affiliations

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

Full Text

References

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