Filimidou Ioanna, Orfanidou Myrsini, Goulas Antonis, Giouleme Olga, Polyzos Stergios Α
First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Second Propaedeutic Medical Department, School of Medicine, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Curr Obes Rep. 2025 Jun 4;14(1):51. doi: 10.1007/s13679-025-00643-x.
The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial. Fibroblast growth factor-21 (FGF-21) has been proposed to be associated with NAFLD, but data on its circulating levels in patients with NAFLD are to date conflicting.
The synthesis and comparison of data on circulating FGF-21 between patients with NAFLD and controls without NAFLD.
A comprehensive literature search was conducted in PubMed, Cochrane Library and Scopus, complemented by hand-searching. Forty-four observational studies with overall 15,563 participants (9548 controls and 6015 NAFLD patients) were included in the study.
Circulating FGF-21 was higher in patients with NAFLD compared to controls (standardized mean difference [SMD]: 0.61; 95% confidence interval [CI]: 0.44, 0.77; p < 0.00001). Subgroup analysis showed higher FGF-21 levels in patients with nonalcoholic steatohepatitis (NASH) compared to controls (SMD: 1.30; 95% CI: 0.35, 2.24; p = 0.007), but not between hepatic steatosis and controls, or hepatic steatosis and NASH. Furthermore, the findings were more robust in the subgroup of studies with NASH-related cirrhosis than those without them (p = 0.0004). Sensitivity analysis further supported the findings. Heterogeneity was high in all comparisons. Meta-regression analyses showed that FGF-21 SMD between NAFLD patients and controls was positively associated with the rate of patients with type 2 diabetes mellitus per study, and this could explain 49.2% of the heterogeneity among studies.
Circulating FGF-21 levels were higher in NAFLD patients than controls, which may be possibly attributed to those with advanced disease (NASH and related cirrhosis). Circulating fibroblast growth factor-21 levels were higher in patients with nonalcoholic fatty liver disease compared to controls. This is primarily attributed to the higher levels observed in patients with advanced disease (steatohepatitis and related cirrhosis).
非酒精性脂肪性肝病（NAFLD）的发病机制是多因素的。成纤维细胞生长因子21（FGF - 21）被认为与NAFLD有关，但迄今为止，关于其在NAFLD患者体内循环水平的数据存在矛盾。
合成并比较NAFLD患者与无NAFLD对照者循环FGF - 21的数据。
在PubMed、Cochrane图书馆和Scopus中进行全面的文献检索，并辅以手工检索。该研究纳入了44项观察性研究，共15563名参与者（9548名对照者和6015名NAFLD患者）。
与对照者相比，NAFLD患者的循环FGF - 21水平更高（标准化均值差[SMD]：0.61；95%置信区间[CI]：0.44，0.77；p < 0.00001）。亚组分析显示，与对照者相比，非酒精性脂肪性肝炎（NASH）患者的FGF - 21水平更高（SMD：1.30；95%CI：0.35，2.24；p = 0.007），但在肝脂肪变性患者与对照者之间，以及肝脂肪变性患者与NASH患者之间无差异。此外，在与NASH相关肝硬化的研究亚组中，研究结果比无肝硬化的亚组更可靠（p = 0.0004）。敏感性分析进一步支持了这些发现。所有比较中的异质性都很高。Meta回归分析显示，每项研究中NAFLD患者与对照者之间的FGF - 21 SMD与2型糖尿病患者的比例呈正相关，这可以解释研究间49.2%的异质性。
NAFLD患者的循环FGF - 21水平高于对照者，这可能归因于患有晚期疾病（NASH和相关肝硬化）的患者。与对照者相比，非酒精性脂肪性肝病患者的循环成纤维细胞生长因子21水平更高。这主要归因于晚期疾病（脂肪性肝炎和相关肝硬化）患者中观察到的较高水平。
