Diagnostic Value of Circulating microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Chronic hepatitis B virus (CHB) infection is the leading cause of hepatocellular carcinoma (HCC). As it is difficult to diagnose the early-stage hepatocellular carcinoma using the existing approaches, better biomarkers are urgently needed and may improve the patients' prognoses. MicroRNAs are the most studied liquid biopsy biomarkers and multiple studies have demonstrated the significant diagnostic value of miRNA in HBV-related hepatocellular carcinoma. In this meta-analysis, we collected 25 studies from 15 researches that included a total of 2290 HBV-related HCC patients and 1551 HBV patients without HCC. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.84 (95% CI: 0.79-0.88), 0.75 (95% CI: 0.69-0.81), 3.42 (95% CI: 2.68-4.35), 0.21 (95% CI: 0.16-0.29), 15.99 (95% CI: 9.89-25.83) and 0.87 (95% CI: 0.83-0.89), respectively. Subgroup analysis indicated that multiple microRNAs, downregulated miRNAs assays, serum type and big sample size had much better accuracy and miR-125b especially, showed a significant diagnostic value. In addition, there is no obvious dignostic difference for HCC from both chronic hepatitis B and liver cirrhosis (LC). Publication bias was not found and Fagan's Nomogram showed valuable clinical utility. In conclusion, circulating microRNAs, particularly the miR-125b, may serve as promising biomarkers for the early diagnosis of HBV-related HCC. However, larger and more rigorous studies are needed to confirm our conclusions.