miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis
Author(s): ,
Manuel Romero-Gómez
Affiliations:
University of Seville, Seville, Spain
Corresponding author. Address: Digestive Diseases Unit, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville, University of Seville, Avda Manuel Siurot s/n, Sevilla 41013, Spain. Tel.: +34 671535780; fax: +34 955 923 101.
,
Rocío Gallego-Durán
Affiliations:
Institute of Biomedicine of Seville, Sevilla, Spain
,
Rocío Muñoz-Hernández
Affiliations:
Institute of Biomedicine of Seville, Sevilla, Spain
,
Ángela Rojas
Affiliations:
Institute of Biomedicine of Seville, Sevilla, Spain
,
Rocío Montero-Vallejo
Affiliations:
University of Seville, Seville, Spain
,
Antonio Gil-Gómez
Affiliations:
University of Seville, Seville, Spain
,
Javier Ampuero
Affiliations:
University of Seville, Seville, Spain
Chang-Hai Liu
Affiliations:
University of Seville, Seville, Spain
EASL LiverTree™. Romero Gomez M. Dec 1, 2018; 256774
Prof. Manuel Romero Gomez
Prof. Manuel Romero Gomez

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Graphical abstract

Graphical abstract

miRNA-34a, miRNA-122 and miRNA-192 helped to distinguish NAFLD and NASH severity. The correlation of miRNA expression between serum and liver tissue was inconsistent. miRNA-122 showed moderate accuracy to distinguish NAFLD from healthy controls. miRNA-34a showed moderate accuracy to distinguish NASH from NAFL.

Background & Aims

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 and negative likelihood ratios, diagnostic odds ratio and area under the curve (AUC) for the diagnosis of NAFLD or non-alcoholic steatohepatitis (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 upregulation. miRNA-122 was upregulated in every scenario used to distinguish NAFLD severity. 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 upregulated in every scenario of NAFL, NASH and fibrosis.

Lay summary

microRNAs are deregulated in non-alcoholic fatty liver disease. The microRNAs, miRNA-34a, miRNA-122 and miRNA-192, were identified as potential biomarkers of non-alcoholic fatty liver and non-alcoholic steatohepatitis, at different stages of disease severity. The correlation between miRNA expression in the serum and in liver tissue was inconsistent, or even inverse.

Keyword(s)
Non-alcoholic fatty liver disease, miRNA, Expression profile, Diagnostic accuracy
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