ArticleDiscover oncology2026
Assessment of the diagnostic performance and influencing factors of AFP and PIVKA-II in hepatocellular carcinoma.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAccurate early diagnosis of hepatocellular carcinoma (HCC) remains challenging due to limitations in serum biomarkers like alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), which are prone to false-positive and false-negative results.
methodsTo identify factors influencing AFP and PIVKA-II levels and their impact on diagnostic performance, this retrospective study analyzed data from 495 patients with confirmed HCC and 261 controls with chronic liver disease (CLD) or cirrhosis (LC). Multivariate analysis identified independent determinants of discordant biomarker profiles.
resultsIn non-HCC patients, elevated alanine aminotransferase (ALT) and total bilirubin (TBIL), and decreased albumin (ALB) were independently associated with false-positive biomarker results. In HCC patients, lower aspartate aminotransferase (AST), lower gamma-glutamyl transferase (GGT), lower red blood cell (RBC) counts, non-viral etiology, smaller tumor size, and absence of extrahepatic metastasis or vascular invasion were independently associated with false-negative results. For diagnosing HCC overall, PIVKA-II (area under the curve [AUC] = 0.886) outperformed AFP (AUC = 0.800, p < 0.0001), and their combination further improved accuracy (AUC = 0.900). This combined strategy showed superior performance particularly in patients with normal TBIL, ALB, or RBC levels, and for detecting smaller tumors (< 3 cm).
conclusionPatient-specific clinical and laboratory factors significantly influence AFP and PIVKA-II levels, affecting diagnostic accuracy. Our findings support the combined use of both biomarkers, especially in patients with preserved liver function, to improve HCC detection and inform refined diagnostic algorithms in CLD/LC populations.
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