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Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma—a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®

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Abstract

Objectives

The recognition of arterial phase hyperenhancement (APHE) and washout during the late phase is key for correct diagnosis of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS). This meta-analysis was conducted to compare SonoVue®-enhanced and Sonazoid®-enhanced ultrasound in the assessment of HCC enhancement and diagnosis.

Methods

Studies were included in the analysis if they reported data for HCC enhancement in the arterial phase and late phase for SonoVue® or in the arterial phase and Kupffer phase (KP) for Sonazoid®. Forty-two studies (7502 patients) with use of SonoVue® and 30 studies (2391 patients) with use of Sonazoid® were identified. In a pooled analysis, the comparison between SonoVue® and Sonazoid® CEUS was performed using chi-square test. An inverse variance weighted random-effect model was used to estimate proportion, sensitivity, and specificity along with 95% confidence interval (CI).

Results

In the meta-analysis, the proportion of HCC showing APHE with SonoVue®, 93% (95% CI 91–95%), was significantly higher than the proportion of HCC showing APHE with Sonazoid®, 77% (71–83%) (p < 0.0001); similarly, the proportion of HCC showing washout at late phase/KP was significantly higher with SonoVue®, 86% (83–89%), than with Sonazoid®, 76% (70–82%) (p < 0.0001). The sensitivity and specificity for the detection of APHE plus late-phase/KP washout detection in HCC were also higher with SonoVue® than with Sonazoid® (sensitivity 80% vs 52%; specificity 80% vs 73% in studies within unselected patient populations).

Conclusion

APHE and late washout in HCC are more frequently observed with SonoVue® than with Sonazoid®. This may affect the diagnostic performance of CEUS in the diagnosis of HCCs.

Clinical relevance statement

Meta-analysis data show the presence of key enhancement features for diagnosis of hepatocellular carcinoma is different between ultrasound contrast agents, and arterial hyperenhancement and late washout are more frequently observed at contrast-enhanced ultrasound with SonoVue® than with Sonazoid®.

Key Points

• Dynamic enhancement features are key for imaging-based diagnosis of HCC.

• Arterial hyperenhancement and late washout are more often observed in HCCs using SonoVue®-enhanced US than with Sonazoid®.

• The existing evidence for contrast-enhanced US may need to be considered being specific to the individual contrast agent.

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Abbreviations

APHE:

Arterial-phase hyperenhancement

CEUS:

Contrast-enhanced ultrasound

CI:

Confidence interval

FLL:

Focal liver lesion

FN:

False negative

FP:

False positive

HCC:

Hepatocellular carcinoma

KP:

Kupffer phase

QUADAS:

Quality Assessment of Diagnostic Accuracy Studies

TN:

True negative

TP:

True positive

UCA:

Ultrasound contrast agent

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Acknowledgements

We gratefully thank Martin Krix and Ningyan Shen of Bracco Imaging for their valuable support in the literature search and statistical analysis.

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Authors and Affiliations

  1. Department of Medical Ultrasound, Laboratory of Novel Optoacoustic (Ultrasonic) Imaging, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Jie Ren

  2. Department of Ultrasound, Laboratory of Ultrasound Medicine, West China Hospital of Sichuan University, Chengdu, China

    Qiang Lu

  3. Department of Ultrasound, the First Medical Center, Chinese PLA General Hospital, Beijing, China

    Xiang Fei

  4. Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

    Yi Dong

  5. Radiology, University of Verona, Verona, Italy

    Mirko D´Onofrio

  6. King‘s College London, Radiology, London, United Kingdom

    Paul S. Sidhu

  7. Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Salem and Permancence, Bern, Switzerland

    Christoph F. Dietrich

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Correspondence to Christoph F. Dietrich.

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The scientific guarantor of this publication is Prof. Christoph F Dietrich.

Conflict of interest

Paul S. Sidhu was Principal Investigator for Phase 3 clinical trials for SonoVue and Sonazoid.

Paul S. Sidhu has received lecture fees from GE healthcare, Philips, Siemens, Bracco, Samsung.

Paul S. Sidhu has received research support from GE and Samsung

Christoph F Dietrich was Principal Investigator for Phase 3 clinical trials for SonoVue.

Christoph F Dietrich has received lecture fees from Bracco, Siemens, Mindray, Hitachi, JAZZ, and Janssen.

Christoph F Dietrich and Paul S. Sidhu has received research support from Mindray, GE Healthcare, Fresenius, Youkey, and Schallware.

The other authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

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Ren, J., Lu, Q., Fei, X. et al. Assessment of arterial-phase hyperenhancement and late-phase washout of hepatocellular carcinoma—a meta-analysis of contrast-enhanced ultrasound (CEUS) with SonoVue® and Sonazoid®. Eur Radiol (2023). https://doi.org/10.1007/s00330-023-10371-2

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