ArticleHepatology communications2026
Validation of longitudinal biomarker screening algorithms for HCC detection in patients with cirrhosis.
Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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16 authors.
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Abstract
backgroundBlood-based biomarker panels, including GALAD, have been proposed as an alternative to abdominal ultrasound for hepatocellular carcinoma (HCC) surveillance. Studies suggest longitudinal evaluation of biomarkers can improve test performance; however, no large studies have validated these findings.
methodsWe leveraged the HCC Early Detection Strategy (HEDS) study (n=1019 patients with cirrhosis; 99 incident HCC) and Texas HCC Consortium (THCCC) (n=2345 patients with cirrhosis; 126 incident HCC) to compare the performance of fixed-threshold GALAD (cutoff of -1.36), and 4 longitudinal algorithms: longitudinal GALAD, PALAD, mFB-ALAD, and mPEB-ALAD. The HEDS cohort was used to derive longitudinal algorithms, and external validation was performed in THCCC. Patient-level sensitivity and test-level false-positive rate (FPR) were examined overall and across subgroups by age, sex, and cirrhosis etiology.
resultsIn THCCC, fixed-threshold GALAD had higher sensitivity in the 6 months before HCC diagnosis (71.4%, 95% CI: 62.9%-81.7%) than longitudinal GALAD (55.1%, 95% CI: 49.3-66.4), PALAD (55.1%, 95% CI: 50.0%-70.5%), mPEB-ALAD (53.1%, 95% CI: 43.6%-62.0%), and mFB-ALAD (42.9%, 95% CI: 32.3-48.5). However, fixed-threshold GALAD had a higher FPR (25.4%, 95% CI: 23.7%-26.9%) compared with longitudinal GALAD (15.0%, 95% CI: 12.8%-15.8%), PALAD (13.0%, 95% CI: 10.2%-14.6%), and mFB-ALAD (11.2%, 95% CI: 9.6%-12.1%) but comparable to mPEB-ALAD (22.9%, 95% CI: 21.2%-23.8%). In subgroup analyses, fixed-threshold GALAD had the highest FPR in males (35.6%) and those aged ≥65 (43.5%); longitudinal algorithms had significantly lower FPRs in subgroups but with lower sensitivity for HCC.
conclusionsImprovements in FPRs with longitudinal GALAD algorithms, as compared with fixed-threshold GALAD, are offset by significantly decreased sensitivity for HCC detection.
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