Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency - Archive ouverte HAL
Article Dans Une Revue Seminars in Liver Disease Année : 2023

Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency

Mathias Ruiz
  • Fonction : Auteur
Florence Lacaille
  • Fonction : Auteur
Christina Schrader
  • Fonction : Auteur
Monica Pons
  • Fonction : Auteur
Piotr Socha
  • Fonction : Auteur
Aleksander Krag
  • Fonction : Auteur
Ekkehard Sturm
  • Fonction : Auteur
Pavel Strnad
  • Fonction : Auteur
  • PersonId : 1091843

Résumé

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.
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Dates et versions

hal-04288515 , version 1 (20-11-2023)

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Mathias Ruiz, Florence Lacaille, Christina Schrader, Monica Pons, Piotr Socha, et al.. Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency. Seminars in Liver Disease, 2023, 43 (03), pp.258-266. ⟨10.1055/a-2122-7674⟩. ⟨hal-04288515⟩
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