Sex, genotype, and liver volume progression as risk of hospitalization determinants in autosomal dominant polycystic liver disease.
ADPLD
PCLD
PRKCSH
SEC63
TLV
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
13 Dec 2023
13 Dec 2023
Historique:
received:
22
08
2023
revised:
04
12
2023
accepted:
10
12
2023
medline:
16
12
2023
pubmed:
16
12
2023
entrez:
15
12
2023
Statut:
aheadofprint
Résumé
Autosomal dominant polycystic liver disease (ADPLD) is a rare condition with a female preponderance, mainly based on pathogenic variants in two genes, PRKCSH and SEC63. Clinically, ADPLD is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and American centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease. We analyzed an international multicenter cohort of 265 patients with ADPLD harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes (nTLV) and PLD-related hospitalization (liver event) as primary clinical endpoints. Classifying individual nTLV into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. Additionally, disease severity, defined by age at first liver event, was significantly more pronounced in females and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease in addition to imaging-based prognostication. Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid TLV-progression is associated with the greatest odds of PLD-related hospitalization.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Autosomal dominant polycystic liver disease (ADPLD) is a rare condition with a female preponderance, mainly based on pathogenic variants in two genes, PRKCSH and SEC63. Clinically, ADPLD is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and American centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease.
METHODS
METHODS
We analyzed an international multicenter cohort of 265 patients with ADPLD harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes (nTLV) and PLD-related hospitalization (liver event) as primary clinical endpoints.
RESULTS
RESULTS
Classifying individual nTLV into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. Additionally, disease severity, defined by age at first liver event, was significantly more pronounced in females and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease in addition to imaging-based prognostication.
CONCLUSIONS
CONCLUSIONS
Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid TLV-progression is associated with the greatest odds of PLD-related hospitalization.
Identifiants
pubmed: 38101549
pii: S0016-5085(23)05603-2
doi: 10.1053/j.gastro.2023.12.007
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.