# Differentiation of AFP-negative hepatocellular carcinoma from other intrahepatic malignant lesions by a noninvasive predictive model based on Sonazoid contrast-enhanced ultrasound

**Authors:** Qian Zhang, Zhilong Liu, Ruining Wang, Lele Song, Wenwen Fan, Ping Liang, Liping Liu

PMC · DOI: 10.3389/fonc.2025.1623670 · Frontiers in Oncology · 2025-07-17

## TL;DR

This study created a non-invasive model using ultrasound and clinical features to accurately distinguish AFP-negative hepatocellular carcinoma from other liver cancers.

## Contribution

A novel nomogram combining Sonazoid contrast-enhanced ultrasound and clinical features for diagnosing AFPN-HCC.

## Key findings

- The model achieved 83.64% accuracy with high sensitivity and specificity.
- Key predictors included tumor number, arterial phase enhancement, and Kupffer phase washout.
- Calibration and decision curve analyses confirmed strong clinical utility.

## Abstract

This study aimed to develop and validate a non-invasive predictive model, which was a reliable nomogram to accurately differentiate AFPN-HCC from other intrahepatic malignant lesions.

This study enrolled 165 patients with malignant focal liver lesions, including AFPN-HCC (n=85) and other intrahepatic malignant lesions (n=80). Data were analyzed to screen for risk factors phase by using LASSO regression as well as univariate and multivariate logistic regression analysis. We constructed a model and developed a nomogram. Then using the area under the curve, Hosmer-Lemeshow test, calibration curves, decision curve analysis, and 1,000 bootstraps to assess and internally validate the model performance. We calculated the optimal threshold, sensitivity, specificity, positive and negative predictive value, and accuracy of the prediction model.

LASSO and multivariate logistic regression analyses indicated that tumor number, necrosis in tumor, arterial phase enhancement pattern, arterial phase perfusion velocity, and Kupffer phase degree of washout were the significant predictors to differentiate AFPN-HCC from OM. The AUC was 0.886, and the AUC of internal validation was 0.865. The optimal critical value of the predicted value was 0.524, with a sensitivity of 82.35%, specificity of 85.00%, positive predicted value of 85.37%, negative predicted value of 81.93%, and an accuracy of 83.64%. The P value of the Hosmer-Lemeshow test was 0.592. The calibration plots showed a high concordance of prediction. The decision curve analysis showed excellent net benefits.

Our nomogram has excellent discrimination, calibration and clinical utility by combining SCEUS and clinical features, which may help clinicians improve the diagnostic performance for AFPN-HCC, contributing to individualized treatment.

## Linked entities

- **Diseases:** hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}
- **Diseases:** KP (MESH:D000210), necrosis (MESH:D009336), hepatic metastases (MESH:D009362), focal liver lesions (MESH:D008107), liver cirrhosis (MESH:D008103), deaths (MESH:D003643), pancreatic cancer (MESH:D010190), allergies (MESH:D004342), HCC (MESH:D006528), intrahepatic malignant lesions (MESH:D009369), hepatic lymphomas (MESH:D008223), OM (MESH:D001932), hypertension (MESH:D006973), liver tumors (MESH:D008113), hepatic neuroendocrine tumor (MESH:D018358), ICC (MESH:D018281), malignant hepatic mesothelioma (MESH:D000086002), dysplastic (MESH:D004416), diabetes mellitus (MESH:D003920)
- **Chemicals:** bilirubin (MESH:D001663), triglyceride (MESH:D014280), Sonazoid (MESH:C069727), uric acid (MESH:D014527), DP (-), Gd-EOB-DTPA (MESH:C073590), cholesterol (MESH:D002784), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12312008/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12312008/full.md

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Source: https://tomesphere.com/paper/PMC12312008