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Meta-Analysis
. 2025 Jul 9;25(1):509.
doi: 10.1186/s12876-025-04097-2.

The impact of serum neuregulin 4 (NRG-4) levels on non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis

Mohammad Amin Tapak  1 , Smko Rashidian Glolan  1 , Yousef Moradi  2
Affiliations
Meta-Analysis

The impact of serum neuregulin 4 (NRG-4) levels on non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis

Mohammad Amin Tapak et al. BMC Gastroenterol. .

Abstract

Purpose: The aim of this systematic review and meta-analysis was to assess the association between serum neuregulin 4 (Nrg4) levels and non-alcoholic fatty liver disease (NAFLD).

Methods: A comprehensive search was performed across Web of Science, EMBASE, Medline (PubMed), and Scopus to find all original published works in NAFLD up to March 2024. Studies were limited to case-control observational studies on humans. After removing duplicated studies, studies were screened based on predefined inclusion and exclusion criteria. The Joanna Briggs Institute checklist (JBI) was used for assessing the quality of case-control studies. The strength of the relationship was assessed by the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). All statistical analyses were performed using Stata 17.0.

Results: Five case-control articles with 323 cases and 308 controls were included in the meta-analysis. The pooled mean ages were 42.6 years for the NAFLD group and 38.0 years for the control group. The pooled estimated OR between Nrg4 and NAFLD was 0.72 (95% CI: 0.67-0.77). The analysis shows that with increasing age (B: 1.381; SE: 0.732; P-value: 0.200; 95% CI: 0.771, 4.534), waist circumference (B: 0.076; SE: 0.041; P-value: 0.207; 95% CI: 0.002, 0.256) and TG levels (B: 0.0426; SE: 0.023; P-value: 0.212; 95% CI: -0.058, 0.143), the association of the Nrg4 index with incident NAFLD increased. Furthermore, the strength of the association between the Nrg4 index and incident NAFLD decreased with increasing levels of ALT (B: -0.124; SE: 0.119; P-value: 0.407; 95% CI: -0.638, 0.389) and HDL (B: -0.221; SE: 0.130; P-value: 0.232; 95% CI: -0.783, 0.340).

Conclusion: In summary, the findings from this meta-analysis strongly suggest that Nrg4 exerts a protective effect against the development of NAFLD. The evidence indicates that measuring Nrg4 levels holds significant promise for facilitating the early diagnosis and prognostication of NAFLD. However, it's essential to note that further research with larger sample sizes and more accurate study designs is needed to corroborate these findings and establish the clinical utility of Nrg4 as a biomarker in the management of NAFLD.

Keywords: Adipokine; Biomarker; Neuregulin 4; Nonalcoholic fatty liver disease.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was not required for this study, as it is a meta-analysis and did not involve the collection of primary data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The process of screening based on title, abstract, and full text
Fig. 2
Fig. 2
Forest plot of the Impact of Serum Neuregulin 4 (NRG‐4) Levels on Non-Alcoholic Fatty Liver Disease (NAFLD)
Fig. 3
Fig. 3
Meta-regression analysis for Assessing the Impact of NRG‐4 Levels on NAFLD based on Age, Waist Circumference, BMI, and Cholesterol
Fig. 4
Fig. 4
Meta-regression analysis for Assessing the Impact of NRG‐4 Levels on NAFLD based on AST, HDL, TG, FBS, and ALT
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