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The following is a summary of “Circulating angiopoietin-like protein 8 (ANGPTL8) and steatotic liver disease related to metabolic dysfunction: an updated systematic review and meta-analysis,” published in the April 2025 issue of Frontiers in Endocrinology by Abdelhameed et al. 

Steatotic liver disease related to metabolic dysfunction was the leading reason of chronic liver disease globally, with angiopoietin-like protein 8 (ANGPTL8) emerging as a potential biomarker for steatosis and steatohepatitis.  

Researchers conducted a retrospective study to synthesize evidence on the association between circulating ANGPTL8 concentrations and steatotic liver diseases, including non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic dysfunction-associated steatotic liver disease (MASLD).  

They searched PubMed/MEDLINE, Cochrane Library, EMBASE, and Web of Science for English-language studies on circulating ANGPTL8 concentrations in adults with NAFLD, MAFLD, or MASLD and controls. A meta-analysis was performed to determine the standardized mean difference (SMD) in circulating ANGPTL8 levels between groups. Study quality and bias risk were assessed using the National Institutes of Health (NIH) quality assessment tool and the Risk of Bias Assessment Tool for Non-Randomized Studies 2 (RoBANS 2).  

The results showed that out of 104 identified publications, 8 studies qualified for the systematic review, and 7 met the criteria for meta-analysis (543 NAFLD or MAFLD cases vs 352 controls). Circulating ANGPTL8 levels were significantly elevated in individuals with NAFLD or MAFLD compared to controls (SMD: 0.62, 95% CI: 0.28-0.97; P <0.001). Substantial heterogeneity was observed among studies, with 6 studies demonstrating a high risk of bias in at least 1 RoBANS 2 domain.  

Investigators concluded that the findings presented current comprehensive evidence indicating higher circulating ANGPTL8 concentrations in adults with metabolic dysfunction-related steatotic liver disease compared to controls, necessitating large and prospective studies to confirm this association and explore its temporal direction, especially under the new MASLD diagnosis/term, given the need for novel screening/diagnostic biomarkers and drug targets. 

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1574842/full