Observational studyBMC gastroenterology2021
Plasma cell free DNA methylation markers for hepatocellular carcinoma surveillance in patients with cirrhosis: a case control study.
Observational study in BMC gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03804593 (HCCBloodTest for Detection of Hepatocellular Carcinoma), which is not on this map. Cited by 28 papers, 2 of them syntheses 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.
HCCBloodTest for Detection of Hepatocellular Carcinoma (HCC): Marker Performance Validation and Technical Development Study
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Diagnostic accuracy of methylatedFrontiers in endocrinology · 2025Pooled it
- Pooled it
- Cell-free DNA methylation markers in the diagnosis of hepatitis B virus-related- hepatocellular carcinoma: a review.Molecular biology reports · 2026Review
- Diagnostic and prognostic performance ofClinical transplantation and research · 2026Article
- Diagnostic Utility of FAR1 Methylation Levels in Hepatocellular Carcinoma Patients Undergoing Liver Transplantation.Annals of transplantation · 2026Article
- Advances in Epigenomic Sequencing and Their Applications in Cancer Diagnostics.Precision chemistry · 2025Review
- Role of Liquid Biopsy for Early Detection, Prognosis, and Therapeutic Monitoring of Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Review
- Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV.Hepatology international · 2025Article
- Genome-Wide Methylation Sequencing to Identify DNA Methylation Markers for Early-stage Hepatocellular Carcinoma in Liver and Blood.Journal of experimental & clinical cancer research : CR · 2025Article
- Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective.Clinical epigenetics · 2025Review
- The Current Role of Circulating Cell-Free DNA in the Management of Hepatocellular Carcinoma.Cancers · 2025Review
- Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications.Clinical and molecular hepatology · 2025Review
- Genome-Wide DNA Methylation Markers Associated With Metabolic Liver Cancer.Gastro hep advances · 2025Article
- Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.Epigenetics · 2024Article
- Review
- Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.Current issues in molecular biology · 2024Review
- Review
- Battle of the biopsies: Role of tissue and liquid biopsy in hepatocellular carcinoma.Journal of hepatology · 2024Review
- Transcriptomic era of cancers in females: new epigenetic perspectives and therapeutic prospects.Frontiers in oncology · 2024Review
- Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, primarily due to failed early detection. HCC screening is recommended among individuals with cirrhosis using biannual abdominal ultrasound, for earlier tumor detection, administration of curative treatment, and improved survival. Surveillance by imaging with or without biomarkers such as alpha-fetoprotein (AFP) remains suboptimal for early stage HCC detection. Here we report on the development and assessment of methylation biomarkers from liquid biopsies for HCC surveillance in cirrhotic patients.
methodsDNA methylation markers including the HCCBloodTest (Epigenomics AG) and a DNA-methylation panel established by next generation sequencing (NGS) were assessed using a training/testing design. The NGS panel algorithm was established in a training study (41 HCC patients; 46 cirrhotic non-HCC controls). For testing, plasma samples were obtained from cirrhotic patients (Child class A or B) with (60) or without (103) early stage HCC (BCLC stage 0, A, B). The assays were then tested using blinded sample sets and analyzed by preset algorithms.
resultsThe HCCBloodTest and the NGS panel exhibited 76.7% and 57% sensitivities at 64.1% and 97% specificity, respectively. In a post-hoc analysis, a combination of the NGS panel with AFP (20 ng/mL) achieved 68% sensitivity at 97% specificity (AUC = 0.9).
conclusionsMethylation biomarkers in cell free plasma DNA provide a new alternative for HCC surveillance. Multiomic panels comprising DNA methylation markers with other biological markers, such as AFP, provide an option to further increase the overall clinical performance of surveillance via minimally invasive blood samples.
trial registrationTest set study-ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.
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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.