Clonal haematopoiesis and risk of chronic liver disease
(2023) In Nature 616(7958). p.747-754- Abstract
- Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals... (More)
- Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response. © 2023, The Author(s), under exclusive licence to Springer Nature Limited. (Less)
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- author
- Wong, W.J. ; Niroula, A. LU and Natarajan, P.
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cell, chronic wasting disease, gene expression, health risk, injury, public health, animal, clonal hematopoiesis, complication, fibrosis, genetics, hepatitis, inflammation, liver cirrhosis, mouse, nonalcoholic fatty liver, Animals, Clonal Hematopoiesis, Fibrosis, Hepatitis, Inflammation, Liver Cirrhosis, Mice, Non-alcoholic Fatty Liver Disease
- in
- Nature
- volume
- 616
- issue
- 7958
- pages
- 8 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85152522037
- pmid:37046084
- ISSN
- 0028-0836
- DOI
- 10.1038/s41586-023-05857-4
- language
- English
- LU publication?
- yes
- id
- 5d0874c2-0e95-4769-96cd-ee4072496b31
- date added to LUP
- 2023-11-06 13:59:56
- date last changed
- 2023-11-20 11:36:48
@article{5d0874c2-0e95-4769-96cd-ee4072496b31,
abstract = {{Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P < 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). To assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P < 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response. © 2023, The Author(s), under exclusive licence to Springer Nature Limited.}},
author = {{Wong, W.J. and Niroula, A. and Natarajan, P.}},
issn = {{0028-0836}},
keywords = {{cell; chronic wasting disease; gene expression; health risk; injury; public health; animal; clonal hematopoiesis; complication; fibrosis; genetics; hepatitis; inflammation; liver cirrhosis; mouse; nonalcoholic fatty liver; Animals; Clonal Hematopoiesis; Fibrosis; Hepatitis; Inflammation; Liver Cirrhosis; Mice; Non-alcoholic Fatty Liver Disease}},
language = {{eng}},
number = {{7958}},
pages = {{747--754}},
publisher = {{Nature Publishing Group}},
series = {{Nature}},
title = {{Clonal haematopoiesis and risk of chronic liver disease}},
url = {{http://dx.doi.org/10.1038/s41586-023-05857-4}},
doi = {{10.1038/s41586-023-05857-4}},
volume = {{616}},
year = {{2023}},
}