Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

source extracted confidence: high 2026-04-09
#biomarkers #carcinoma-hepatocellular #humans #liver-neoplasms #protein-precursors

Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Xing et al., 2018 | Hepatobiliary Pancreat Dis Int | Meta Analysis

Citation

Xing Hao, Zheng Yi-Jie, ... Yang Tian. Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis. Hepatobiliary Pancreat Dis Int. 2018-Dec;17(6):487-495. doi:10.1016/j.hbpd.2018.09.009

Abstract

BACKGROUND: As a promising biomarker of hepatocellular carcinoma (HCC), protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-II with alpha-fetoprotein (AFP) in the diagnosis of HCC. DATA SOURCES: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-II and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve (ROC) was employed to evaluate the diagnostic accuracy of each marker. RESULTS: Thirty-one studies were included. The pooled sensitivity (95% CI) of PIVKA-II and AFP was 0.66 (0.65-0.68) and 0.66 (0.65-0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity (95% CI) was 0.89 (0.88-0.90) and 0.84 (0.83-0.85), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.856 (0.817-0.895) and 0.770 (0.728-0.811), respectively. Subgroup analysis showed that PIVKA-II was superior to AFP in terms of the AUC for both small HCC (< 3 cm) [0.863 (0.825-0.901) vs 0.717 (0.658-0.776)] and large HCC (≥ 3 cm) [0.854 (0.811-0.897) vs 0.729 (0.682-0.776)]; for American [0.926 (0.897-0.955) vs 0.698 (0.594-0.662)], European [0.772 (0.743-0.801) vs 0.628 (0.594-0.662)], Asian [0.838 (0.812-0.864) vs 0.785 (0.764-0.806)] and African [0.812 (0.794-0.840) vs 0.721 (0.675-0.767)] HCC patients; and for HBV-related [0.909 (0.866-0.951) vs 0.714 (0.673-0.755)] and mixed-etiology [0.847 (0.821-0.873) vs 0.794 (0.772-0.816)] HCC. CONCLUSION: This meta-analysis indicates that PIVKA-II is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

Key Findings

Thirty-one studies were included. The pooled sensitivity (95% CI) of PIVKA-II and AFP was 0.66 (0.65-0.68) and 0.66 (0.65-0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity (95% CI) was 0.89 (0.88-0.90) and 0.84 (0.83-0.85), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.856 (0.817-0.895) and 0.770 (0.728-0.811), respectively. Subgroup analysis showed that PIVKA-II was superior to AFP in terms of the AUC for both small HCC (< 3 cm) [0.86

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Biomarkers
  • Carcinoma, Hepatocellular
  • Humans
  • Liver Neoplasms
  • Protein Precursors
  • Prothrombin
  • Publication Bias
  • ROC Curve
  • alpha-Fetoproteins

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: vitamin-k-cancer

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09