ArticleProceedings of the National Academy of Sciences of the United States of America2019
Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05494853 (Novel Biomarker Assay for HCC Detection and Monitoring Piedmont Transplant Institute and Genetron Health, Inc.), which is not on this map. Cited by 111 papers, 2 of them syntheses that pooled it.
What it found
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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.
Novel Biomarker Assay for HCC Detection and Monitoring Piedmont Transplant Institute and Genetron Health, Inc.
Who cites it
111 citing papers in PubMed, 2 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Utility of Liquid Biopsy Analysis in Detection of Hepatocellular Carcinoma, Determination of Prognosis, and Disease Monitoring: A Systematic Review.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2020Pooled it
- Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta-analysis.Cancer medicine · 2020Pooled it
- Cell-free DNA methylation markers in the diagnosis of hepatitis B virus-related- hepatocellular carcinoma: a review.Molecular biology reports · 2026Review
- Liquid biopsy-based multi-omics approach for early detection of hepatocellular carcinoma (ASCEND-Hep): a multiphase prospective development and validation study.BMC medicine · 2026Article
- Whole-Genome Bisulfite Sequencing Identifies Blood-Based DNA Methylation Biomarker for Hepatocellular Carcinoma.Molecular carcinogenesis · 2026Article
- Liquid biopsies in precision oncology for older adults with cancer.NPJ precision oncology · 2026Review
- Potential oncogene VPS72 in hepatocellular carcinoma: prognostic and immune infiltration implications.European journal of medical research · 2026Article
- Assessment of Circulating Tumor DNA for Early Detection of Hepatocellular Carcinoma in Alpha-Fetoprotein-Negative Patients With Cirrhotic Nodules.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Review
- China Liver Cancer Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2024 Edition).Liver cancer · 2025Article
- The genomic and epigenomic abnormalities of plasma cfDNA as liquid biopsy biomarkers to detect hepatocellular carcinoma: a multicenter cohort study.Journal of hematology & oncology · 2025Article
- Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care.Cancers · 2025Review
- The methylation signature of hepatocellular carcinoma trajectory based on pseudotime and chronological time for predicting precancerous patients.The oncologist · 2025Article
- Prediction of Therapeutic Response and Prognosis in Ovarian Cancer Patients With Plasma Circulating Biomarkers.Cancer innovation · 2025Article
- Development and clinical applications of liquid biopsy assays in cancer screening.Translational cancer research · 2025Review
- Exam quality of ultrasound and dynamic contrast-enhanced abbreviated MRI and impact on early-stage HCC detection.Abdominal radiology (New York) · 2025Article
- A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024.Journal of liver cancer · 2025Article
- Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications.Clinical and molecular hepatology · 2025Review
- [Current status and prospects for screening early-stage hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Artificial intelligence in hepatocellular carcinoma screening: applications and challenges.Frontiers in medicine · 2025Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 6 institutions in 2 countries.
Funding
Abstract
Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
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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.