Biomarkers Associated With Future Severe Liver Disease in Children With Alpha-1-Antitrypsin Deficiency.
Alpha-1-Antitrypsin
Cholestasis
Gamma Glutamyl Transferase
Polymer
Portal Hypertension
Journal
Gastro hep advances
ISSN: 2772-5723
Titre abrégé: Gastro Hep Adv
Pays: Netherlands
ID NLM: 9918350485906676
Informations de publication
Date de publication:
2024
2024
Historique:
received:
16
02
2024
accepted:
19
04
2024
medline:
17
9
2024
pubmed:
17
9
2024
entrez:
16
9
2024
Statut:
epublish
Résumé
Children with alpha-1-antitrypsin deficiency (AATD) exhibit a wide range of liver disease outcomes from portal hypertension and transplant to asymptomatic without fibrosis. Individual outcomes cannot be predicted. Liver injury in AATD is caused by the accumulation in hepatocytes of the mutant Z alpha-1-antitrypsin (AAT) protein, especially the toxic, intracellular polymerized conformation. AATD patients have trace Z polymer detectable in serum with unknown significance. The Childhood Liver Disease Research Network is an NIH consortium for the study of pediatric liver diseases, including AATD. We obtained data and samples with the aim of identifying biomarkers predictive of severe AATD liver disease. We analyzed prospective AATD Childhood Liver Disease Research Network data and serum samples in 251 subjects from 2007 to 2015 for outcomes and Z polymer levels. Fifty-eight of 251 had clinically evident portal hypertension (CEPH) at enrollment, and 10 developed CEPH during follow-up. Higher Z AAT polymer levels were associated with existing CEPH ( High circulating Z polymer levels and high GGT early in life are associated with future CEPH in AATD, and the use of predictive cutoffs may assist in future clinical trial design.
Sections du résumé
Background and Aims
UNASSIGNED
Children with alpha-1-antitrypsin deficiency (AATD) exhibit a wide range of liver disease outcomes from portal hypertension and transplant to asymptomatic without fibrosis. Individual outcomes cannot be predicted. Liver injury in AATD is caused by the accumulation in hepatocytes of the mutant Z alpha-1-antitrypsin (AAT) protein, especially the toxic, intracellular polymerized conformation. AATD patients have trace Z polymer detectable in serum with unknown significance.
Methods
UNASSIGNED
The Childhood Liver Disease Research Network is an NIH consortium for the study of pediatric liver diseases, including AATD. We obtained data and samples with the aim of identifying biomarkers predictive of severe AATD liver disease.
Results
UNASSIGNED
We analyzed prospective AATD Childhood Liver Disease Research Network data and serum samples in 251 subjects from 2007 to 2015 for outcomes and Z polymer levels. Fifty-eight of 251 had clinically evident portal hypertension (CEPH) at enrollment, and 10 developed CEPH during follow-up. Higher Z AAT polymer levels were associated with existing CEPH (
Conclusion
UNASSIGNED
High circulating Z polymer levels and high GGT early in life are associated with future CEPH in AATD, and the use of predictive cutoffs may assist in future clinical trial design.
Identifiants
pubmed: 39280919
doi: 10.1016/j.gastha.2024.04.010
pii: S2772-5723(24)00060-8
pmc: PMC11401556
doi:
Types de publication
Journal Article
Langues
eng
Pagination
842-850Informations de copyright
© 2024 The Authors.