Mechanisms of Fibrosis Development in Nonalcoholic Steatohepatitis.
Drug Development
Metabolic Syndrome
Noninvasive Biomarkers
Pediatric Obesity
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
02
09
2019
revised:
18
11
2019
accepted:
20
11
2019
pubmed:
12
2
2020
medline:
16
2
2021
entrez:
12
2
2020
Statut:
ppublish
Résumé
Nonalcoholic fatty liver disease is the most prevalent liver disease worldwide, affecting 20%-25% of the adult population. In 25% of patients, nonalcoholic fatty liver disease progresses to nonalcoholic steatohepatitis (NASH), which increases the risk for the development of cirrhosis, liver failure, and hepatocellular carcinoma. In patients with NASH, liver fibrosis is the main determinant of mortality. Here, we review how interactions between different liver cells culminate in fibrosis development in NASH, focusing on triggers and consequences of hepatocyte-macrophage-hepatic stellate cell (HSC) crosstalk. We discuss pathways through which stressed and dead hepatocytes instigate the profibrogenic crosstalk with HSC and macrophages, including the reactivation of developmental pathways such as TAZ, Notch, and hedgehog; how clearance of dead cells in NASH via efferocytosis may affect inflammation and fibrogenesis; and insights into HSC and macrophage heterogeneity revealed by single-cell RNA sequencing. Finally, we summarize options to therapeutically interrupt this profibrogenic hepatocyte-macrophage-HSC network in NASH.
Identifiants
pubmed: 32044315
pii: S0016-5085(20)30169-4
doi: 10.1053/j.gastro.2019.11.311
pmc: PMC7682538
mid: NIHMS1568905
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1913-1928Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK116620
Pays : United States
Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
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