miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND & AIM: microRNAs (miRNAs) are deregulated in non-alcoholic fatty liver disease (NAFLD) and have been proposed as useful markers for the diagnosis and stratification of disease severity. We conducted a meta-analysis to identify the potential usefulness of miRNA biomarkers in the diagnosis and stratification of NAFLD severity. METHODS: After a systematic review, circulating miRNA expression consistency and mean fold-changes were analysed using a vote-counting strategy. The sensitivity, specificity, positive (PLRs) and negative likelihood ratios (NLRs), diagnostic odds ratio (DOR) and area under the curve (AUC) for the diagnosis of NAFLD or NASH were pooled using a bivariate meta-analysis. Deeks' funnel plot was used to assess the publication bias. RESULTS: Thirty-seven studies of miRNA expression profiles and six studies of diagnostic accuracy were ultimately included in the quantitative analysis. miRNA-122 and miRNA-192 showed consistent up-regulation. miRNA-122 was up-regulated in every scenario used to distinguish NAFLD severities. The miRNA expression correlation between the serum and liver tissue was inconsistent across studies. miRNA-122 distinguished NAFLD from healthy controls with an AUC of 0.82 (95% CI: 0.75 - 0.89), and miRNA-34a distinguished non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver (NAFL) with an AUC of 0.78 (95% CI: 0.67 - 0.88). CONCLUSION: miRNA 34a, miRNA-122 and miRNA-192 were identified as potential diagnostic markers to segregate NAFL from NASH. Both miRNA-122, in distinguishing NAFLD from healthy controls, and miRNA-34a, in distinguishing NASH from NAFL, showed moderate diagnostic accuracy. miRNA-122 was up-regulated in every scenario of NAFL, NASH and fibrosis. LAY SUMMARY: The miRNA-34a, miRNA-122 and miRNA-192, were identified as potential biomarkers for NAFL and NASH at different disease severity. The miRNAs expression correlation between serum and liver tissue was inconsistent or even inverse.