ArticleGastroenterology2025
Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis.
Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- 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
- Machine learning-driven evaluation of protein kinase D3 as a co-diagnostic biomarker in hepatocellular carcinoma.Journal of Zhejiang University. Science. B · 2026Article
- Development and validation of risk stratification models for hepatocellular cancer: A framework from the translational liver cancer consortium.Hepatology (Baltimore, Md.) · 2026Article
- Risk Assessment and Prediction of Hepatocellular Carcinoma in Noncirrhotic Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Global Advances in Hepatocellular Carcinoma Research and Therapy in 2025.Cancer innovation · 2026Review
- Risk-stratified surveillance for hepatocellular carcinoma.Hepatology communications · 2026Review
- Chemoprevention of hepatocellular carcinoma by next-generation antipsychotic aripiprazole.Hepatology (Baltimore, Md.) · 2026Article
- Refining surveillance of hepatocellular carcinoma in chronic hepatitis B through biomarker-based risk stratification.Hepatology communications · 2026Review
- Unraveling the genetic susceptibility to HBV-related liver cancer: The role of virus-host immune interactions.Hepatology (Baltimore, Md.) · 2026Article
- Association between the aMAP risk score and mortality in the MASLD/MetALD/ALD patient population: a cohort study.Frontiers in medicine · 2026Article
- Prognostic value of salt-inducible kinase 2 expression in advanced hepatocellular carcinoma treated with sorafenib or lenvatinib: a propensity score-matched cohort study.American journal of cancer research · 2026Article
- Putative Imprinting Control Regions with Aberrant Blood-Based DNA Methylation are Associated with Hepatocellular Carcinoma Risk.Journal of hepatocellular carcinoma · 2026Article
- Hepatocellular Carcinoma Precursor Lesions: From Pathological Basis to Risk Stratification and Precision Intervention.Journal of hepatocellular carcinoma · 2026Review
- Early screening for liver cancer must be performed.World journal of hepatology · 2025Review
- Persisting challenges in the early detection of hepatocellular carcinoma.Expert review of anticancer therapy · 2025Review
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Authors and funding
31 authors.
Funding
Abstract
BACKGROUND &
aimsHepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.
methodsMolecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events.
resultsOf 2156 patients with cirrhosis in the Texas HCC Consortium, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared with low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios for incident HCC of 7.51 (95% CI, 4.42-12.8) and 4.20 (95% CI, 2.52-7.01), respectively. Of 1328 patients with cirrhosis in the HCC early detection strategy, PAaM identified 201 high-risk (15%), 540 intermediate-risk (41%), and 587 low-risk (44%) patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate-risk groups were associated with sub-distribution hazard ratios for incident HCC of 6.54 (95% CI, 3.85-11.1) and 1.77 (95% CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease and cured hepatitis C infection.
conclusionsPAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.
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