ArticleGastroenterology2026
Changes in Liver Disease Etiology Support a Lower Alpha-Fetoprotein Threshold for Hepatocellular Carcinoma Screening.
Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Distinct Alpha-Fetoprotein Trajectories Preceding Hepatocellular Carcinoma Diagnosis: A Latent Class Mixed-Model Analysis.Cancers · 2026Article
- Optimizing hepatocellular carcinoma screening in the era of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease: time to lower the alpha-fetoprotein threshold.Journal of gastrointestinal oncology · 2026Article
- Multi-Target HCC Blood Test Demonstrates Consistent Performance Across Subgroups of Patients with Chronic Liver Disease.Cancers · 2026Article
- From bench to bedside: Molecular mechanisms, diagnostic tools, and therapeutic strategies in liver fibrosis.Liver research (Beijing, China) · 2026Review
- MiR-4725-3p acts as an oncogene and prognostic biomarker in hepatocellular carcinoma.World journal of surgical oncology · 2026Article
- Development of a longitudinal predictive model for hepatocellular carcinoma occurrence in patients with chronic hepatitis B.Scientific reports · 2026Article
- Global Advances in Hepatocellular Carcinoma Research and Therapy in 2025.Cancer innovation · 2026Review
- Risk Scores for Stratifying Hepatocellular Carcinoma and Optimizing Surveillance Strategies.Cancers · 2026Review
- Monocyte to apolipoprotein A1 ratio as a novel biomarker for hepatocellular carcinoma: a retrospective study.Translational gastroenterology and hepatology · 2026Article
- Performance of GAAD and GALAD Biomarker Panels for HCC Detection in Patients with MASLD or ALD Cirrhosis.Cancers · 2025Article
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19 authors.
Funding
Abstract
BACKGROUND &
aimsSerum alpha-fetoprotein (AFP) is a key component of hepatocellular carcinoma (HCC) screening, but its test characteristics are uncertain as alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) rates increase.
methodsWe evaluated AFP trends at HCC diagnosis and estimated its test performance for HCC screening in cirrhosis using Veterans Health Administration (VHA) and United Network for Organ Sharing data.
resultsAmong the 40,399 VHA patients diagnosed with HCC between 2001 and 2021, median AFP at HCC diagnosis declined over time and was highest in active-hepatitis C (HCV) (32.7 vs cured-HCV 8.3, ALD 9.0, MASLD 7.7 ng/mL). Among the 28,170 VHA patients with cirrhosis receiving care in 2019 (9.6% active-HCV, 43% cured-HCV, 24% ALD, 14% MASLD), 1,029 developed HCC in 2019. At AFP thresholds ≥20 and ≥10 ng/mL, the overall sensitivity/specificity for HCC screening was 31.7%/98.5% and 41.9%/94.1%, respectively. Lowering the AFP threshold to ≥10 ng/mL increased sensitivity with minimal reductions in specificity across all liver disease etiologies: active-HCV (sensitivity/specificity: 43.7% to 60.7%/92.6% to 83.0%), cured-HCV (32.5% to 41.5%/99.0% to 94.7%), ALD (22.8% to 32.3%/99.2% to 95.1%), and MASLD (21.7% to 29.9%/99.4% to 96.7%). Analysis of United Network for Organ Sharing (26,213 patients with HCC) resulted in similar increases in test sensitivity as the AFP threshold declined from ≥20 to ≥10 ng/mL (overall: 31.8% to 48.7%; active-HCV: 36.7% to 58.6%, cured-HCV: 21.4% to 36.4%, MASLD: 19.1% to 33.4%, and ALD: 15.9% to 27.1%).
conclusionsFor HCC screening in MASLD, ALD, and cured-HCV cirrhosis, reducing the AFP threshold to ≥10 ng/mL would substantially increase sensitivity while maintaining very high specificity.
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