Background The most promising serum biomarkers for hepatocellular carcinoma (HCC) patients include PIVKA-II, AFP, and AFP-L3. Nevertheless, the effectiveness of combining biomarkers is still up for debate. This meta-analysis aimed to evaluate the diagnostic accuracy of PIVKA-II+AFP and PIVKA-II+AFP-L3. Methods Following a systematic search of the literature in PubMed, Medline, Web of Science, Scopus, the Cochrane Library, Embase, Google Scholar and CINAHL, thirty relevant papers were found. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were evaluated using a random-effects model. Results The pooled sensitivity, specificity and DOR values of PIVKA-II+AFP were 0,79, 0,83, and 24,95, respectively; which were slightly lower to those of PIVKA-II+AFP-L3 (0,77, 0,88, and 29,73, respectively) except for sensitivity . Furthermore, PIVKA-II+AFP-L3 presented higher diagnostic accuracy (AUC=0,923) than did PIVKA-II+AFP (AUC=0,895). Neither threshold effects nor continent or etiology of HCC were found to be sources of heterogeneity. Interestingly, we demonstrated proof of publication bias for DOR values using Egger’s regression test (p < 0,05) and funnel plots. Sensitivity analysis proved the strong reliability of this meta-analysis. Conclusion The combined assay of PIVKA-II+AFP-L3 seemed to be more adequate than PIVKA-II+AFP for the diagnosis of HCC. Hence, diagnostic tests combining many biomarkers will be clinically significant for HCC decision-making processes.

The authors have declared no competing interest.

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The author(s) received no specific funding for this work.

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