Tapak Mohammad Amin, Glolan Smko Rashidian, Moradi Yousef
Student Research committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Social Determinants of the Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
BMC Gastroenterol. 2025 Jul 9;25(1):509. doi: 10.1186/s12876-025-04097-2.
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).
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.
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).
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.
本系统评价和荟萃分析旨在评估血清神经调节蛋白4（Nrg4）水平与非酒精性脂肪性肝病（NAFLD）之间的关联。
全面检索了Web of Science、EMBASE、Medline（PubMed）和Scopus，以查找截至2024年3月在NAFLD领域发表的所有原创研究。研究仅限于针对人类的病例对照观察性研究。去除重复研究后，根据预先定义的纳入和排除标准对研究进行筛选。使用乔安娜·布里格斯研究所检查表（JBI）评估病例对照研究的质量。通过比值比（OR）和相应的95%置信区间（CI）评估关联强度。所有统计分析均使用Stata 17.0进行。
五项病例对照研究（共323例病例和308例对照）纳入了荟萃分析。NAFLD组的合并平均年龄为42.6岁，对照组为38.0岁。Nrg4与NAFLD之间的合并估计OR为0.72（95%CI：0.67 - 0.77）。分析表明，随着年龄（B：1.381；SE：0.732；P值：0.200；95%CI：0.771，4.534）、腰围（B：0.076；SE：0.041；P值：0.207；95%CI：0.002，0.256）和甘油三酯水平（B：0.0426；SE：0.023；P值：0.212；95%CI： - 0.058，0.143）的增加，Nrg4指数与新发NAFLD的关联增强。此外，随着丙氨酸氨基转移酶（ALT）水平（B： - 0.124；SE：0.119；P值：0.407；95%CI： - 0.638，0.389）和高密度脂蛋白（HDL）水平（B： - 0.221；SE：0.130；P值：0.232；95%CI： - 0.783，0.340）的增加，Nrg4指数与新发NAFLD之间的关联强度减弱。
总之，本荟萃分析的结果强烈表明，Nrg4对NAFLD的发展具有保护作用。证据表明，检测Nrg4水平对于促进NAFLD的早期诊断和预后评估具有重要前景。然而，必须指出的是，需要进行更大样本量和更精确研究设计的进一步研究，以证实这些发现并确立Nrg4作为NAFLD管理中生物标志物的临床效用。
