Combining Pentraxin-3 and AFP increases sensitivity to 0.92 for hepatocellular carcinoma diagnosis in chronic liver disease

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Clinica chimica acta; international journal of clinical chemistry Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Amdetsion Gedion Yilma, Murali Arvind R, Pan Chun-Wei, Miranda Clive, Sueldo Alexandra, Tebeje Hiwot… PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider combining Pentraxin-3 and AFP to improve sensitivity for hepatocellular carcinoma diagnosis.

This systematic review and meta-analysis assessed the diagnostic performance of Pentraxin-3 (PTX3) compared to Alpha-fetoprotein (AFP) in adults with chronic liver disease evaluated for suspected or established hepatocellular carcinoma. The analysis included 1179 participants, with 362 having confirmed hepatocellular carcinoma. The study setting was not reported, and follow-up duration was not reported.

Diagnostic metrics for PTX3 alone included a sensitivity of 0.79, a specificity of 0.83, and an AUC of 0.876. In contrast, AFP alone demonstrated a sensitivity of 0.76, a specificity of 0.81, and an AUC of 0.849. When combined, PTX3 and AFP yielded a sensitivity of 0.92, a specificity of 0.85, and an AUC of 0.942. The diagnostic odds ratio for the combination was 65.8.

The authors note that PTX3 demonstrated diagnostic performance comparable to AFP. However, the combination of PTX3 and AFP was associated with higher pooled sensitivity. No adverse events, serious adverse events, discontinuations, or tolerability data were reported. Funding or conflicts of interest were not reported. The practice relevance suggests that combining these markers may improve diagnostic accuracy over using AFP alone.

Study Details

Study typeMeta analysis

Sample sizen = 362

EvidenceLevel 1

PublishedJun 2026

PMID41985832

View Original Abstract ↓

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: PTX3 demonstrated diagnostic performance comparable to AFP; however, the combination of PTX3 and AFP was associated with higher pooled sensitivity.