Diagnostic Value of Liver Contrast-enhanced Ultrasound in Early Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Background: Hepatocellular carcinoma is the sixth most common cancer in the world, and its incidence rate will continue to increase. Contrast-enhanced ultrasound (CEUS) is feasible as a rapid examination for early hepatocellular carcinoma diagnosis. However, considering the possible causes of false positives caused by ultrasound, its diagnostic value is still controversial. Therefore, the study conducted a meta-analysis to evaluate the application value of CEUS in the early diagnosis of hepatocellular carcinoma.

Methods: The PubMed, Cochrane Library, Embase, Ovid Technologies (OVID), China National Knowledge Infrastructure (CNKI), Chongqing VIP Information (VIP), and Wanfang databases were searched to retrieve articles on the use of CEUS for the early diagnosis of hepatocellular carcinoma. The literature quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) quality assessment tool. The meta-analysis was performed using STATA 17.0 to fit the bivariate mixed effects model, calculated sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and corresponding 95% CI, summary receiver operating characteristic curves (SROC), area under the curve (AUC), and 95% confidence interval (CI). The publication bias of the included literature was evaluated using the DEEK funnel plot.

Results: Ultimately, 9 articles, comprising 1,434 patients, were included in the meta-analysis. The heterogeneity test found that I>50%, using a random effects model. The results of the meta-analysis showed that the CEUS had a combined sensitivity of 0.92 (95% CI: 0.86-0.95), a combined specificity of 0.93 (95% CI: 0.56-0.99), a combined PLR of 13.47 (95% CI: 1.51-120.46), a combined NLR of 0.09 (95% CI: 0.05-0.14), a combined DOR of 154.16 (95% CI: 15.93-1,492.02), a diagnostic score of 5.04 (95% CI: 2.77-7.31), and a combined AUC of 0.95 (95% CI: 0.93-0.97). The correlation coefficient of the threshold-effect analysis was 0.13 (P>0.05). The results of the regression analysis showed that the country of publication (P=0.14) and the size of the lesion nodules (P=0.46) were not sources of heterogeneity.

Conclusions: Liver CEUS has an advantage in the early diagnosis of hepatocellular carcinoma, with high sensitivity and specificity, and has clinical application value.