Abdelhameed Farah, Lagojda Lukasz, Kite Chris, Dallaway Alexander, Mustafa Attia, Than Nwe Ni, Kassi Eva, Randeva Harpal S, Kyrou Ioannis
Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
Institute for Cardiometabolic Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
Front Endocrinol (Lausanne). 2025 Apr 10;16:1574842. doi: 10.3389/fendo.2025.1574842. eCollection 2025.
Steatotic liver disease related to metabolic dysfunction is the most common cause of chronic liver disease globally. The spectrum of this condition includes steatosis and steatohepatitis and was previously referred to as non-alcoholic fatty liver disease (NAFLD) but has been renamed as metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently as metabolic dysfunction-associated steatotic liver disease (MASLD). Angiopoietin-like protein 8 (ANGPTL8), also known as betatrophin or lipasin, regulates triglycerides and has emerged as a potential novel biomarker for steatosis/steatohepatitis. Therefore, this systematic review aimed to identify and synthesize the evidence on the possible association of circulating ANGPTL8 concentrations with NAFLD, MAFLD or MASLD.
PubMed/MEDLINE, Cochrane Library, EMBASE, and Web of Science were searched for studies published in English reporting circulating ANGPTL8 concentrations in adults with NAFLD or MAFLD or MASLD and controls. A meta-analysis was performed, reporting the standardized mean difference (SMD) of circulating ANGPTL8 concentrations between these two groups. Study quality and risk of bias were assessed using the NIH quality assessment tool and RoBANS 2, respectively.
Of the 104 identified publications, eight studies were eligible for this systematic review, whilst seven were also eligible for meta-analysis (543 NAFLD or MAFLD cases 352 controls). Circulating ANGPTL8 concentrations were significantly higher in patients with NAFLD or MAFLD compared with controls (SMD: 0.62, 95%CI: 0.28-0.97; p<0.001). Considerable heterogeneity was noted among these studies, with six studies having high risk of bias in at least one RoBANS 2 domain.
These findings present up-to-date comprehensive evidence indicating that adults with steatotic liver disease related to metabolic dysfunction exhibit higher circulating ANGPTL8 concentrations compared with controls. Given the need for novel screening/diagnostic biomarkers for steatosis/steatohepatitis, as well for additional drug targets, large and prospective studies are required to confirm this association and explore its temporal direction, particularly under the new MASLD diagnosis/term.
与代谢功能障碍相关的脂肪性肝病是全球慢性肝病最常见的病因。这种疾病的范围包括脂肪变性和脂肪性肝炎，以前被称为非酒精性脂肪性肝病（NAFLD），但现已更名为代谢功能障碍相关脂肪性肝病（MAFLD），最近又称为代谢功能障碍相关脂肪性肝病（MASLD）。血管生成素样蛋白8（ANGPTL8），也称为β-促胰岛素分泌素或脂联素，可调节甘油三酯，已成为脂肪变性/脂肪性肝炎的一种潜在新型生物标志物。因此，本系统评价旨在识别和综合关于循环ANGPTL8浓度与NAFLD、MAFLD或MASLD之间可能关联的证据。
在PubMed/MEDLINE、Cochrane图书馆、EMBASE和科学网中检索以英文发表的报告NAFLD、MAFLD或MASLD成人及对照组循环ANGPTL8浓度的研究。进行荟萃分析，报告这两组之间循环ANGPTL8浓度的标准化平均差（SMD）。分别使用美国国立卫生研究院质量评估工具和RoBANS 2评估研究质量和偏倚风险。
在104篇已识别的出版物中，8项研究符合本系统评价的条件，7项研究也符合荟萃分析的条件（543例NAFLD或MAFLD病例对352例对照）。与对照组相比，NAFLD或MAFLD患者的循环ANGPTL8浓度显著更高（SMD：0.62，95%CI：0.28 - 0.97；p<0.001）。这些研究之间存在相当大的异质性，6项研究在至少一个RoBANS 2领域存在高偏倚风险。
这些发现提供了最新的综合证据，表明与代谢功能障碍相关的脂肪性肝病成人与对照组相比，循环ANGPTL8浓度更高。鉴于需要用于脂肪变性/脂肪性肝炎的新型筛查/诊断生物标志物以及额外的药物靶点，需要进行大型前瞻性研究来证实这种关联并探索其时间方向，特别是在新的MASLD诊断/术语下。
