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Hepatic molecular signatures highlight the sexual dimorphism of Non-Alcoholic SteatoHepatitis (NASH)
- Source :
- Hepatology, Hepatology, 2020, ⟨10.1002/HEP.31312⟩, Hepatology (Baltimore, Md.), Hepatology, Wiley-Blackwell, 2020, ⟨10.1002/HEP.31312⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Background and Aims Nonalcoholic steatohepatitis (NASH) is considered as a pivotal stage in nonalcoholic fatty liver disease (NAFLD) progression, given that it paves the way for severe liver injuries such as fibrosis and cirrhosis. The etiology of human NASH is multifactorial, and identifying reliable molecular players and/or biomarkers has proven difficult. Together with the inappropriate consideration of risk factors revealed by epidemiological studies (altered glucose homeostasis, obesity, ethnicity, sex, etc.), the limited availability of representative NASH cohorts with associated liver biopsies, the gold standard for NASH diagnosis, probably explains the poor overlap between published “omics”‐defined NASH signatures. Approach and Results Here, we have explored transcriptomic profiles of livers starting from a 910‐obese‐patient cohort, which was further stratified based on stringent histological characterization, to define “NoNASH” and “NASH” patients. Sex was identified as the main factor for data heterogeneity in this cohort. Using powerful bootstrapping and random forest (RF) approaches, we identified reliably differentially expressed genes participating in distinct biological processes in NASH as a function of sex. RF‐calculated gene signatures identified NASH patients in independent cohorts with high accuracy. Conclusions This large‐scale analysis of transcriptomic profiles from human livers emphasized the sexually dimorphic nature of NASH and its link with fibrosis, calling for the integration of sex as a major determinant of liver responses to NASH progression and responses to drugs.
- Subjects :
- Male
Transcriptomic signatures
[SDV]Life Sciences [q-bio]
Steatohepatitis and Metabolic Liver Disease
NASH
nutritional and metabolic diseases
Random forest Accepted Article
Original Articles
Middle Aged
digestive system
digestive system diseases
[SDV] Life Sciences [q-bio]
Sexual dimorphism
Sex Factors
Liver
Non-alcoholic Fatty Liver Disease
Risk Factors
Humans
Original Article
Female
Obesity
Human medicine
Transcriptome
Random forest
Subjects
Details
- Language :
- English
- ISSN :
- 02709139 and 15273350
- Database :
- OpenAIRE
- Journal :
- Hepatology, Hepatology, 2020, ⟨10.1002/HEP.31312⟩, Hepatology (Baltimore, Md.), Hepatology, Wiley-Blackwell, 2020, ⟨10.1002/HEP.31312⟩
- Accession number :
- edsair.pmid.dedup....90b98f5ba675730d9b8e7aa60ea68422