DAA shows effective against HCV, however, direct evidence on the effects of antiviral therapy on HCV-HCC remains limited. Furthermore, the development of non-invasive markers for screening of HCC presents a challenge during the last decades. Fortunately and interestingly, accumulating evidence shows that aberrant miRNAs expression profiles have been associated with the development of HCC[6]. Previous study showed that miRNAs were correlated in hepatocarcinogenic effect of HCV[26]. However, different reports have the discrepancies due to samples, technical variations and analysis methods. Therefore, we conducted this meta-analysis to evaluate the clinical value of circulating miRNAs in diagnosis of HCV-HCC.
According to our results, circulating miRNAs showed high diagnostic accuracy for HCV-HCC detection, with SEN of 0.83 (95% CI, 0.79–0.87), SPE of 0.77 (95% CI, 0.71–0.82), PLR of 3.6 (95% CI, 2.8–4.7), NLR of 0.21 (95% CI, 0.16–0.29), DOR of 17 (95% CI, 12–28) and AUC of 0.87 (95% CI, 0.84–0.90). A significant improvement in the sensitivity was observed when circulating miRNAs combined with AFP than using alone (P < 0.000). Moreover, we have characterized the role of miRNA clusters as diagnostic and prognostic markers for distinction of HCV-HCC from CHC and HCV-LC subgroup.
Currently, available diagnostic or prognostic biomarkers have limited accuracy for HCC[27]. AFP is the most widely used for HCC, however, serum AFP levels are related to both HCC and benign liver diseases, such as hepatitis and cirrhosis [28–29]. Precious studies have demonstrated that miRNAs could be served as high-precision detection of HCC biomarker[30]. In this present study, although the DOR of AFP is higher than miRNAs alone (33 versus 17), no statistical difference of OA value was observed. Similarly, He et al. found SEN and AUC-SROC of AFP for HCC were significantly less than miRNAs, while the DOR of AFP was higher than miRNAs[31]. The possible reasons for this are associated with the cut-off value of AFP, stage of HCC, and tumor size. Growing evidence indicated that miRNAs had a better performance compared with AFP in detection of early-stage HCV-HCC from CHC and LC, such as miR-331-3p, miR-23b-3p, miR-19a, miR-223, miR-122, miR-199a, miR-16, miR-101-1 and miR-221[10, 14, 21, 24]. In addition, the OA value of miRNAs combined with AFP had a significantly higher accuracy for HCV-HCC than AFP or miRNAs alone (P < 0.000). These findings together with previous results indicated that circulating miRNAs could be used as putative diagnostic and prognostic biomarkers for HCV-HCC.
In the subgroup analyses, our findings revealed that miRNAs from plasma had higher precision detection for HCV-HCC than that from serum. The DOR of plasm and serum miRNAs was 64 (95% CI 25–164) versus 14 (95% CI 8–23), and AUC was 0.87 (95% CI 0.84–0.90) versus 0.85 (95% CI 0.82–0.88), respectively. Previous studies reported that miRNAs concentration in plasma is higher than serum due to more proteins in plasma [32–33]. However, the opposite results were also found in serum [31]. Therefore, further studies are needed to confirm application of specimen types in clinical practice. Interestingly, our study revealed differences in DOR (237 versus 12) when selecting miRNA clusters for HCV-HCC diagnosis. However, the miRNAs panel has not been definitely decided yet due to differentially expressed circulating miRNAs in HCV-HCC[13, 23]. All the above researches suggested that multiple miRNAs panel may be a promising prospect for application as a non-invasive method for HCV-HCC.
Although the results are promising, several limitations need to be addressed. First, some related studies, such as letters, editorials, case reports and conference proceedings, were not included. Second, most studies included in this meta-analysis were from Egypt, having an adverse effect on population selection bias. Third, different cut-off values were not extracted due to limited data, which may result in a latent problem when interpreting the results. Therefore, the results of this study need more higher quality studies for confirmation in the future.