ArticleGut2021
Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 95 citations in OpenAlex.
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
- Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms and Biomarkers for Precision Therapy.Cancers · 2026Review
- Diet-Microbiota-Immune Interactions in Hepatocellular Carcinoma: An Immunometabolic and Spatial Perspective.Nutrients · 2026Review
- HCV-Induced Hepatocarcinogenesis: Molecular Mechanisms, Persistent Cancer Risk, and Future Perspectives.Biomedicines · 2026Review
- Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.Journal of advanced research · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Review
- Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.International journal of cancer · 2025Review
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- A prognostic signature based on insulin-signaling-pathway genes for hepatocellular carcinoma.Discover oncology · 2025Article
- Perturbation of the circadian clock in chronic diseases involving organ fibrosis.The Journal of clinical investigation · 2025Review
- Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response.Clinical and experimental medicine · 2025Review
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- Current and emerging strategies for the prevention of hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Modelling hepatocellular carcinoma microenvironment phenotype to evaluate drug efficacy.Scientific reports · 2025Article
- The Role of Epigenetic Mechanisms in the Treatment of GI Cancers.Current cancer drug targets · 2025Review
- Perspective of the risk and molecular mechanisms of hepatocellular carcinoma after HCV eradication in the post-DAA era: Correspondence to editorial on "Unmet needs in the post-direct-acting antivirals era: The risk and molecular mechanisms of hepatocellular carcinoma after hepatitis C virus eradication".Clinical and molecular hepatology · 2024Article
- Pathogenesis and management of metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma: a narrative review.Ewha medical journal · 2024Review
- An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection.Nature communications · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 9 institutions in 5 countries.
Funding
Abstract
objectiveHepatocellular carcinoma (HCC) is the fastest-growing cause of cancer-related mortality with chronic viral hepatitis and non-alcoholic steatohepatitis (NASH) as major aetiologies. Treatment options for HCC are unsatisfactory and chemopreventive approaches are absent. Chronic hepatitis C (CHC) results in epigenetic alterations driving HCC risk and persisting following cure. Here, we aimed to investigate epigenetic modifications as targets for liver cancer chemoprevention.
designLiver tissues from patients with NASH and CHC were analysed by ChIP-Seq (H3K27ac) and RNA-Seq. The liver disease-specific epigenetic and transcriptional reprogramming in patients was modelled in a liver cell culture system. Perturbation studies combined with a targeted small molecule screen followed by i
resultsIn patients, CHC and NASH share similar epigenetic and transcriptomic modifications driving cancer risk. Using a cell-based system modelling epigenetic modifications in patients, we identified chromatin readers as targets to revert liver gene transcription driving clinical HCC risk. Proof-of-concept studies in a NASH-HCC mouse model showed that the pharmacological inhibition of chromatin reader bromodomain 4 inhibited liver disease progression and hepatocarcinogenesis by restoring transcriptional reprogramming of the genes that were epigenetically altered in patients.
conclusionOur results unravel the functional relevance of metabolic and virus-induced epigenetic alterations for pathogenesis of HCC development and identify chromatin readers as targets for chemoprevention in patients with chronic liver diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.