Protein induced by vitamin K absence or antagonist II as a prognostic marker in hepatocellular carcinoma patients with normal serum alpha-fetoprotein levels
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Alpha-fetoprotein (AFP) has been the primary biomarker for hepatocellular carcinoma (HCC), but a subset of patients with HCC have normal serum levels of AFP (<20 ng/mL). Reliable biomarkers for predicting prognosis in this population remain limited. Protein induced by vitamin K absence or antagonist II (PIVKA-II) has emerged as a promising diagnostic marker for HCC, but its prognostic value for patients with normal AFP has not been well established. Therefore, this study investigated its prognostic significance in such patients. METHODS: We retrospectively analyzed 330 consecutive treatment-naïve patients with HCC who had normal serum levels of AFP and were diagnosed between 2020 and 2023 at Taipei Veterans General Hospital. Patients were stratified into two groups according to serum levels of PIVKA-II (>100 vs ≤100 mAU/mL). Prognostic factors for overall survival (OS) were assessed using multivariate Cox proportional-hazards models. RESULTS: There were 169 (51.2%) patients in the study population who had elevated PIVKA-II levels (>100 mAU/mL). These patients demonstrated more aggressive tumor characteristics, including larger tumor size, multinodularity, macrovascular invasion, and extrahepatic metastases compared to those with PIVKA-II ≤100 mAU/mL, despite having comparable liver functional reserves. Patients with high PIVKA-II levels were also less likely to undergo curative treatment (53.3% vs 83.2%, p < 0.001). After a median follow-up of 17 months (interquartile range: 8.0-27.0), 50 patients had died, and the overall 3-year OS rate was 77%. OS was significantly lower in the high-PIVKA-II group than the low-PIVKA-II group (54.9% vs 87.1%, p < 0.001). Multivariate analysis identified elevated PIVKA-II as an independent predictor for poor OS (hazard ratio: 2.422, 95% CI, 1.128-5.198, p = 0.023). CONCLUSION: Serum PIVKA-II is an independent prognostic biomarker for patients with HCC who have normal AFP levels and can be used to stratify patients into distinct risk groups.
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4415412111