Circulating lipoprotein(a) levels and steatotic liver disease related to metabolic dysfunction in adults: an updated systematic review and meta-analysis

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously defined as non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD), is the leading cause of chronic liver disease worldwide, with a pathophysiological spectrum ranging from steatosis to steatohepatitis and fibrosis. Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein, which is associated with increased cardiovascular disease (CVD) risk and has been recently reported as a potential biomarker for MASLD. This systematic review and meta-analysis aimed to present an updated evidence synthesis on the potential link between circulating Lp(a) concentrations and this prevalent hepatic disease in adults. Methods: PubMed, Embase, CINAHL, and Scopus were searched for eligible studies published in English without a date restriction. Risk of bias (RoB) and study quality were assessed using the Revised RoB Assessment Tool for Nonrandomised Studies (RoBANS 2) and the National Institute of Health quality assessment tool, respectively. Three-level meta-regression performed reporting the pooled mean difference of circulating Lp(a) concentrations between adults with MASLD or NAFLD or MAFLD and controls without these conditions. Results: Twenty-one observational studies were included in this meta-analysis (137,494 cases; 281,261 controls). A three-level meta-analysis resulted in a pooled mean difference of 1.40 mg/dL [95% confidence interval: −2.81, 5.61; p = 0.50], indicating no significant difference in circulating Lp(a) concentrations between patients with MASLD or NAFLD or MAFLD and controls. Considerable between-study heterogeneity was observed (I2 = 95.7%). Conclusion: These findings provide up-to-date, comprehensive evidence indicating that there are no significant differences in circulating Lp(a) concentrations between adults with metabolic-related steatosis/steatohepatitis and controls. This suggests limited potential for circulating Lp(a) as a diagnostic/prognostic biomarker for MASLD, although this biomarker could still be utilized to assess CVD risk in the context of steatotic liver disease. Future prospective studies are required to further explore the clinical utility of circulating Lp(a) as a biomarker in MASLD, particularly for long-term CVD outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024607750, Identifier: CRD42024607750.