Compared with SonoVue® LR-5, Sonazoid® modified LR-5 has better diagnostic sensitivity for hepatocellular carcinoma: a systematic review and meta-analysis.

ABSTRACT

Background: The contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) is a standardized system for reporting liver nodules in patients at risk of developing hepatocellular carcinoma (HCC) and is only recommended for pure blood pool agents such as SonoVue®. A modified LI-RADS was proposed for Sonazoid®, a Kupffer cell-specific contrast agent. This meta-analysis was conducted to compare the diagnostic efficiency of the CEUS LI-RADS for SonoVue® and the modified LI-RADS for Sonazoid®. Methods: The PubMed, Medline, Web of Science, Embase, and Cochrane Library databases were systematically searched to retrieve studies on the diagnostic efficiency of the CEUS LI-RADS algorithms in diagnosing HCC using SonoVue® and/or Sonazoid® from January 2016 to June 2023. Histopathology or imaging follow-up served as the reference standards. Only articles published in English on retrospective or prospective studies with full reports were included in the meta-analysis. A bivariate random-effects model was used. Data pooling, meta-regression, and sensitivity analysis were performed for the meta-analysis. Deeks' funnel plot asymmetry test was used to evaluate publication bias, and the QUADAS-2 tool was used to assess the methodological quality of eligible studies. Results: In total, 26 studies comprising 8,495 patients with 9,244 lesions were included in the meta-analysis. The pooled data results for SonoVue® LI-RADS category 5 (LR-5) and Sonazoid® modified LR-5 were as follows pooled sensitivity 0.68 [95% confidence interval (CI) 0.64-0.73, I2=89.20%; P<0.01] and 0.82 (95% CI 0.74-0.87, I2=85.39%; P<0.01) (P<0.05); pooled specificity 0.93 (95% CI 0.90-0.96, I2=86.52%; P<0.01) and 0.86 (95% CI 0.79-0.91, I2=59.91%; P=0.01) (P<0.05); pooled area under the curve (AUC) 0.86 (95% CI 0.82-0.89) and 0.91 (95% CI 0.88-0.93) (P<0.05), respectively. The meta-regression analysis revealed that the study design, subject enrollment method, and reference standard contributed to the heterogeneity of SonoVue® LR-5, and the number of lesions was a source of heterogeneity for Sonazoid® modified LR-5. The diagnostic performance of the LI-RADS category M (LR-M) algorithms of SonoVue® and Sonazoid® was comparable. Conclusions: The Sonazoid® modified LR-5 algorithm had a higher diagnostic sensitivity, lower specificity, and higher AUC than SonoVue® LR-5.