ArticleMed (New York, N.Y.)2021
A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis.
Article in Med (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 56 citations in OpenAlex.
- Financial Burden of Hepatocellular Carcinoma Screening in Patients With Cirrhosis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2024Trial
- Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.Hepatology (Baltimore, Md.) · 2024Trial
- Validation of Risk Models for Predicting Post-SVR HCC in Real-World Surveillance Across Global Geographic Regions.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Risk Assessment and Prediction of Hepatocellular Carcinoma in Noncirrhotic Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Risk-stratified surveillance for hepatocellular carcinoma.Hepatology communications · 2026Review
- Chemoprevention of hepatocellular carcinoma by next-generation antipsychotic aripiprazole.Hepatology (Baltimore, Md.) · 2026Article
- Research Communication: Serum Metabolomic Signatures Predict Tumour Recurrence After Resection or Ablation in Patients With Early-Stage Hepatocellular Carcinoma.Alimentary pharmacology & therapeutics · 2026Article
- HCC Is the Predominant Liver-Related Event in MASLD: 2-Step Non-Invasive Algorithms to Stratify Risk in Non-Cirrhotic Patients.Journal of hepatocellular carcinoma · 2026Article
- Dual tissue mRNA and serum protein signatures improve risk stratification in hepatocellular carcinoma.NPJ precision oncology · 2025Article
- Improving risk stratification and detection of early HCC using ultrasound-based deep learning models.JHEP reports : innovation in hepatology · 2025Article
- Profiles of HBV DNA integration in humans with hepatitis B virus infection: Insights for antiviral treatment.JHEP reports : innovation in hepatology · 2025Article
- Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs.Disease models & mechanisms · 2025Article
- Patient-Perceived Risk of Hepatocellular Carcinoma and Net Benefit of Surveillance: A Multicenter Survey Study.The American journal of gastroenterology · 2025Article
- Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.Gastroenterology · 2025Article
- A patient-derived HCC spheroid system to model the tumor microenvironment and treatment response.JHEP reports : innovation in hepatology · 2025Article
- Cost-effectiveness of a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis.EClinicalMedicine · 2024Article
- Early warning of hepatocellular carcinoma in cirrhotic patients by three-phase CT-based deep learning radiomics model: a retrospective, multicentre, cohort study.EClinicalMedicine · 2024Article
- Review
- Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.Genes & cancer · 2024Article
- The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.Frontiers in oncology · 2024Review
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Authors and funding
25 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundAccurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this currently remains an unmet need.
methodsA serum-protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in two independent cohorts: validation set 2 (V2): 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy; validation set 3 (V3): 146 patients with advanced liver fibrosis with successfully-treated HCC and cured HCV infection.
findingsAn 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30-4.23). A composite score with serum alpha-fetoprotein (PLSec-AFP) was defined in V1, and validated in V2 (adjusted odds ratio, 3.80 [95%CI, 1.66-8.66]) and V3 (aHR, 3.08 [95%CI, 1.78-5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 vs. 0.186 in V2; 0.196 vs. 0.206 in V3, respectively).
conclusionsThe blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.
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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.