ArticleHepatology (Baltimore, Md.)2022
Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
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- The Wnt/β-catenin-P2-HNF4α feedback loop facilitates colorectal tumorigenesis and malignancy.Journal of translational medicine · 2025Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Nuclear receptors in metabolic, inflammatory, and oncologic diseases: mechanisms, therapeutic advances, and future directions.European journal of medical research · 2025Review
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- Expression landscape of epigenetic genes in human hepatocellular carcinoma.Journal of physiology and biochemistry · 2025Article
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Overexpression ofBioMed research international · 2025Article
- Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocellular carcinoma through stabilizing HNF4α protein.Discover oncology · 2024Article
- Identifying novel mechanisms of per- and polyfluoroalkyl substance-induced hepatotoxicity using FRG humanized mice.Archives of toxicology · 2024Article
- Regulation of hepatic xenosensor function by HNF4alpha.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Unlocking therapeutic potential: exploring cross-talk among emerging nuclear receptors to combat metabolic dysfunction in steatotic liver disease.npj metabolic health and disease · 2024Review
- Role of HNF4α-cMyc Interaction in CDE Diet-Induced Liver Injury and Regeneration.The American journal of pathology · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- Targeting nuclear receptors for NASH/MASH: From bench to bedside.Liver research (Beijing, China) · 2024Article
- Modulation of Hepatocyte Nuclear Factor 4 Alpha (HNF4α): A Critical Mechanism of Disease Progression in Liver Cirrhosis.Cellular and molecular gastroenterology and hepatology · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimsHepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC. APPROACH AND
resultsWe developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K-means clustering, survival, and rank-order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV- and HBV-induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determined. Results revealed a step-wise reduction in HNF4α activity with each progressive stage of pathogenesis. Cluster analysis of LC gene expression data sets using the HNF4α signature showed that loss of HNF4α activity was associated with progression of Child-Pugh class, faster decompensation, incidence of HCC, and lower survival with and without HCC. A moderate decrease in HNF4α activity was observed in NAFLD from normal liver, but a further significant decline was observed in patients from NAFLD to NASH. In HCC, loss of HNF4α activity was associated with advanced disease, increased inflammatory changes, portal vein thrombosis, and substantially lower survival.
conclusionsIn conclusion, these data indicate that loss of HNF4α function is a common event in the pathogenesis of CLDs leading to HCC and is important from both diagnostic and therapeutic standpoints.
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