PMID- 37402396
OWN - NLM
STAT- MEDLINE
DCOM- 20231103
LR  - 20240104
IS  - 1098-8971 (Electronic)
IS  - 0272-8087 (Linking)
VI  - 43
IP  - 3
DP  - 2023 Aug
TI  - Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency.
PG  - 258-266
LID - 10.1055/a-2122-7674 [doi]
AB  - 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.
CI  - Thieme. All rights reserved.
FAU - Ruiz, Mathias
AU  - Ruiz M
AD  - Hepatologie, Gastroenterologie et Nutrition Pediatriques, Hopital Femme Mere 
      Enfant, Hospices civils de Lyon, Health Care Provider of the European Reference 
      Network on Rare Liver Disorders (ERN RARE LIVER), Lyon, France.
FAU - Lacaille, Florence
AU  - Lacaille F
AD  - Service de Gastroenterologie-Nutrition Pediatriques et Unite d'Hepatologie 
      Pediatrique Hopital Universitaire Necker-Enfants Malades, Health Care Provider of 
      the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Paris, 
      France.
FAU - Schrader, Christina
AU  - Schrader C
AD  - 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.
FAU - Pons, Monica
AU  - Pons M
AD  - 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.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas 
      (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
FAU - Socha, Piotr
AU  - Socha P
AD  - The Children's Memorial Health Institute, Department of Gastroenterology, 
      Hepatology, Nutritional Disorders and Pediatrics, Al. Dzieci Polskich, Warszawa, 
      Poland.
FAU - Krag, Aleksander
AU  - Krag A
AD  - Department of Gastroenterology and Hepatology, Odense University Hospital, 
      Odense, Denmark.
FAU - Sturm, Ekkehard
AU  - Sturm E
AD  - Pediatric Gastroenterology and Hepatology, University Children's Hospital 
      Tubingen, Member Center of the European Reference Network on Rare Liver Disorders 
      (ERN RARE LIVER), Tubingen, Germany.
FAU - Bouchecareilh, Marion
AU  - Bouchecareilh M
AD  - University of Bordeaux, CNRS, INSERM, BRIC, U1312, Bordeaux, France.
FAU - Strnad, Pavel
AU  - Strnad P
AD  - 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.
LA  - eng
GR  - SFB 1382 (ID 403224013) and STR 1095/6-1/Deutsche Forschungsgemeinschaft (DFG)/
PT  - Journal Article
PT  - Review
DEP - 20230704
PL  - United States
TA  - Semin Liver Dis
JT  - Seminars in liver disease
JID - 8110297
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - Infant, Newborn
MH  - *alpha 1-Antitrypsin Deficiency/complications/genetics/therapy
MH  - Liver Cirrhosis/genetics/complications
MH  - Genotype
MH  - *Cholestasis/complications
COIS- M.R. received advisory board fees and lecture fees from Takeda, advisory board 
      fees from Grifols, lecture fees from CSL Behring. P.S. received grant support and 
      lecture fees from Grifols and CSL Behring; grant support and advisory board fees 
      from Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals; grant support from 
      Vertex Pharmaceuticals; advisory board fees from GSK, Intellia Pharmaceuticals, 
      Novo Nordisk, Takeda, and Ono Pharmaceuticals; and is supported by the Deutsche 
      Forschungsgemeinschaft (DFG) grants SFB 1382 (ID 403224013) and STR 1095/6-1.
EDAT- 2023/07/05 01:06
MHDA- 2023/11/03 06:44
CRDT- 2023/07/04 19:03
PHST- 2023/11/03 06:44 [medline]
PHST- 2023/07/05 01:06 [pubmed]
PHST- 2023/07/04 19:03 [entrez]
AID - 10.1055/a-2122-7674 [doi]
PST - ppublish
SO  - Semin Liver Dis. 2023 Aug;43(3):258-266. doi: 10.1055/a-2122-7674. Epub 2023 Jul 
      4.