LAUSR

We read with great interest the manuscript of Yang et al. entitled “Perfluorobutane contrast-enhanced ultrasonography (P-CEUS) for the diagnosis of HCC: a systematic review and meta-analysis” [1]. The authors demonstrate that P-CEUS has a high performance for the diagnosis of HCC. We strongly agree with the authors about the importance of the P-CEUS, but there are several critical points that may need to be elucidated so as to augment the validity of the authors’ multifactorial findings. First, in the conclusion section of the abstract, the authors revealed that P-CEUS can significantly improve the diagnostic efficiency of previous contrast-enhanced ultrasound for HCC. However, this study aimed to evaluate the accuracy and reliability of P-CEUS in the diagnosis of HCC and did not compare the diagnostic efficiency between perfluorobutane ultrasound contrast agent and other agents, such as SonoVue, directly. In the P-CEUS versus sulfur hexafluoride CEUS section of the results, the authors revealed that perfluorobutane agent is more stable, can improve the image quality, is not inferior to SonoVue [2], and can distinguish HCC from non-HCC malignant tumors (including metastasis and ICC) [3]. Furthermore, a recent multicenter prospective study including 424 patients found a similar efficacy for Sonazoid and SonoVue in diagnosing focal liver lesions as benign or malignant [4]. Therefore, we consider that P-CEUS significantly improving the diagnostic efficiency of previous CEUS for HCC could not be demonstrated according to the present study and is significantly not rational. Second, regarding the conclusion, the authors found that the sensitivity and specificity of P-CEUS are more valuable than other imaging techniques (such as computer tomography or magnetic resonance imaging). However, in the main text, the authors only illustrated some advantages of P-CEUS by reviewing literatures. For example, Kupffer phase images in P-CEUS can be used to predict hypervascularization of hypointense borderline lesions that are detected on the hepatobiliary phase on enhanced MRI [5], and P-CEUS can improve the accuracy of diagnosis of local recurrence after HCC treatment, compared with CECT [6]. Whereas, there is no quantitative comparison of the sensitivity and specificity between P-CEUS and enhanced MRI and CECT. Therefore, we believe that the conclusion is not reliable. Third, the authors depicted that quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach in the methodological quality of the included studies section. But, in this meta-analysis, quality of evidence assessed by GRADE approach was not reported in the main text. Therefore, we deeply believe that this study is required to further revise. Fourth, this article is a systematic review and metaanalysis of diagnostic test accuracy studies. The authors declared that the study was conducted according to the recommendations of the PRISMA 2009 guidelines. However, the PRISMA-DTA 2015 guidelines may be more appropriate, which reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies [7]. Finally, the authors depicted that the 14 factors of metaregression were classified and compared. But there are only 12 factors in Fig. 5. Furthermore, in the pooled analysis of diagnostic accuracy section of results, Yang et al. depicted that three of the nine studies can confirm and exclude This comment refers to the article available online at https:// doi. org/ 10. 1007/ s0026102103141-5.