Efficacy of serum miRNA test as a non-invasive method to diagnose nonalcoholic steatohepatitis: a systematic review and meta-analysis

Shengliang Xin, Qiao Zhan, Xiaofan Chen, Jinghang Xu, Yanyan Yu, Shengliang Xin, Qiao Zhan, Xiaofan Chen, Jinghang Xu, Yanyan Yu

Abstract

Background: Nonalcoholic steatohepatitis (NASH) is a key turning point during the progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have shown that serum miRNA tests may be effective in the diagnosis of NAFLD. We conducted a meta-analysis to assess the evidence for the diagnostic efficacy of serum miRNAs in patients with NAFLD and its subtype, NASH, in particular.

Methods: After a systematic review, sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) were pooled to determine the efficacy of serum miRNA test for the diagnosis of NAFLD and NASH. Clinical utility was evaluated by Fagan's nomogram and likelihood ratio scattergram. Heterogeneity was evaluated by subgroup analysis and meta-regression. Publication bias was detected by Deeks' funnel plot.

Results: We included 27 trials containing 1775 NAFLD patients (including simple steatosis and NASH) and 586 NASH patients. For NAFLD vs NASH, the pooled sensitivity, specificity, and AUROC were (0.71 vs. 0.74), (0.76 vs. 0.85) and (0.80 vs. 0.86), respectively. Serum miRNA had high accuracy for distinguishing NASH from simple steatosis, with an AUROC of 0.91. Among the most commonly studied serum miRNAs, miRNA-34a showed moderate diagnostic accuracy for NAFLD and the lowest heterogeneity (sensitivity I2 = 5.73%, specificity I2 = 33.16%, AUROC = 0.85). According to subgroup analysis and meta-regression, a lower BMI (< 30 kg/m2) might be a crucial source of heterogeneity.

Conclusions: As a novel non-invasive method, serum miRNA test exhibited robust diagnostic efficacy for NASH. Among these well-studied miRNAs, miRNA-34a was more available for diagnosis. Diagnosis of NAFLD by serum miRNA is more likely to be accurate in patients with BMI ≥ 30 kg/m2.

Keywords: Body mass index; MicroRNA; Nonalcoholic steatohepatitis; Obesity.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Article selection process
Fig. 2
Fig. 2
a: Total sample size in NAFLD trials and NASH trials. b: Total sample size of each target serum miRNA
Fig. 3
Fig. 3
Forest plots and meta-analysis of trials showing pooled sensitivity and specificity (a), PLR and NLR (b) and DOR (c) of serum miRNA for diagnosis of total NAFLD (case vs. control). d: SROC curve of serum miRNA for diagnosis of total NAFLD (case vs. control)
Fig. 4
Fig. 4
Meta-regression analysis of serum miRNA for diagnosis of total NAFLD (case vs. control). The assignment was made as follows: disease (Yes = NASH, No = NAFLD), regulation mode (Yes = upregulation, No = downregulation), geographic region (Yes = Asian, No = Non-Asian), and miRNA profiling (Yes = single miRNA, No = miRNA panel)
Fig. 5
Fig. 5
a: Fagan’s nomogram of serum miRNA for diagnosis of NASH (NAS ≥ 5 vs. < 5). Pre-test probability = 50% (patients with moderate suspicion for NASH), the post-test positive and negative probability of NASH were 83 and 24%, respectively. b: Fagan’s nomogram of serum miRNA for diagnosis of NAFLD (NAFLD vs. healthy control). Pre-test probability = 50% (patients with the moderate suspicion for NAFLD), the post-test positive and negative probability of NAFLD were 75 and 27%, respectively. c: The likelihood ratio scattergram of serum miRNA for diagnosis of NASH (NAS ≥ 5 vs. < 5). LRP: positive likelihood ratio; LRN: negative likelihood ratio; LUQ: left upper quadrant; RUQ: right upper quadrant; LLQ: left lower quadrant; RLQ: right lower quadrant
Fig. 6
Fig. 6
Estimation of the publication bias by Deeks’ funnel plots for all involved trials (a), NAFLD trials (b), NASH trials (c) and miRNA-34a trials (d)

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