ArticlePLoS genetics2019
Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04220151 (Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C), which is not on this map. Cited by 100 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Epigenetic Changes in Hepatocellular Carcinoma Developed After Direct Acting Antiviral Therapy for Chronic Hepatitis C
Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Pooled it
- Viral persistence and host-state remodeling in virus-associated cancers.Archives of microbiology · 2026Review
- HCV-Induced Hepatocarcinogenesis: Molecular Mechanisms, Persistent Cancer Risk, and Future Perspectives.Biomedicines · 2026Review
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- Hepatitis C elimination: is it time to redefine the goals?Nature reviews. Gastroenterology & hepatology · 2026Article
- DNA methylation profiles at hospital admission are associated with subsequent severe COVID-19 outcomes.Clinical epigenetics · 2026Article
- SOX9 and TNFAIP3 dysregulation in HCV-associated HCC after DAA therapy: insights into post-viral oncogenic memory.Infectious agents and cancer · 2026Article
- Liver reprogramming toward hepatocellular carcinoma following hepatitis C sustained virologic response: a narrative review.Translational gastroenterology and hepatology · 2026Review
- Assessment of peripheral gene expression signatures as predictive biomarkers for hepatocellular carcinoma following DAA treatment.Journal, genetic engineering & biotechnology · 2025Article
- Changes in gene expression levels caused by H3K9me3/H3K9ac modifications are associated with BmCPV infection inVirulence · 2025Article
- Bioinformatics Analysis of Persistent Dysregulated Expression of Genes Involved in HCV-Induced Neurological Disorders and Liver Injuries After DAA Treatment Through Weighted Gene Co-Expression Network Analysis.Health science reports · 2025Article
- Silent mutations in coding regions of Hepatitis C virus affect patterns of HCV RNA structures and attenuate viral replication and pathogenesis.Genome biology · 2025Article
- Precision Strategy for Hepatocellular Carcinoma Surveillance after Hepatitis C Cure: Debates across Guidelines.Gut and liver · 2025Review
- HBV-driven host chromatin accessibility changes affect liver metabolic pathways, iron homeostasis and promote a preneoplastic phenotype.Journal of experimental & clinical cancer research : CR · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Article
- The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses.Frontiers in microbiology · 2025Review
- Lipid and immune dysregulation and risk of metabolic disorders after HCV clearance in HIV/HCV-coinfected participants with cACLD: a retrospective study.Frontiers in immunology · 2025Article
- Review
- Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications.Journal of neurovirology · 2024Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 6 countries.
Funding
Abstract
The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic "scarring" of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.
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What Socratic holds
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 Socratic graph.