Pentraxin-3, a complementary biomarker in hepatocellular carcinoma: Systematic review and Meta-analysis

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) diagnosis; however, its sensitivity is limited, especially for early-stage disease and in AFP-negative HCC cases. Pentraxin-3 (PTX3), a marker of local inflammation and angiogenesis, may outperform AFP in detection by reflecting distinct biological pathways involved in hepatocarcinogenesis.

PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov were searched through December 2025 following PRISMA guidelines. Eligible studies included adults with chronic liver disease evaluated for suspected or established HCC. Pooled sensitivity and specificity were calculated using the bivariate Reitsma model, and the overall diagnostic performance was assessed using. sensitivity, specificity, and diagnostic odds ratio, along with determining the area under the curve (AUC).

Five retrospective studies involving 1179 participants, including 362 patients with HCC, met the inclusion criteria. Using the bivariate Reitsma model, the pooled sensitivity and specificity of PTX3 were 0.79 (95% CI 0.74-0.84) and 0.83 (95% CI 0.76-0.88), respectively, with an AUC of 0.876. AFP alone showed a sensitivity of 0.76 (95% CI 0.70-0.80) and specificity of 0.81 (95% CI 0.74-0.86), with an AUC of 0.849. The combined PTX3 + AFP approach had sensitivity of 0.92 (95% CI 0.89-0.94), specificity of 0.85 (95% CI 0.77-0.90), with a DOR of 65.8 and an AUC of 0.942.

PTX3 demonstrated diagnostic performance comparable to AFP; however, the combination of PTX3 and AFP was associated with higher pooled sensitivity.