ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Serum Lipoprotein(a) levels are inversely associated with Metabolic dysfunction-associated steatosis liver disease progression: two cross-sectional studies and a longitudinal study
Wen Guo 1
Fei Lin 2
Chengxiao Yu 1
Jing Lu 1
Pei Qin 1
Xin Zhao 1
Xiaona Li 1
Qun Zhang 1
1. The First Affiliated Hospital With Nanjing Medical University, Nanjing, China
2. Nanjing Medical University, Nanjing, China
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Abstract
Background and Aim: Given that abnormal lipid metabolism is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), this study seeks to investigate the relationship between serum lipoprotein(a) [Lp(a)] levels and the progression or regression of MASLD. Methods: A total of 12,962 participants undergoing transient elastography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University were included in the first cross-sectional study (Study 1). The longitudinal study (Study 2) included 17,661 individuals from the same center, each with at least two health check-ups involving abdominal ultrasonography. Another cross-sectional study (Study 3) included 5,927 individuals from the UK Biobank cohort who had undergone both magnetic resonance imaging proton density fat fraction (MRI-PDFF) and Lp(a) testing. Results: Cross-sectional analysis (Study 1) revealed that elevated Lp(a) levels were inversely correlated with the severity of both hepatic steatosis and fibrosis. Longitudinal data (Study 2) further demonstrated that baseline serum Lp(a) levels were decreased in participants with the incident of MASLD, while increased in participants with the regression of MASLD during the follow-up period. A lower baseline Lp(a) level was an independent factor for new-onset MASLD and non-regression of MASLD: the fully adjusted hazard ratios (HR) were 0.895(95%CI 0.834-0.962, P<0.001) and 0.889 (95%CI 0.8110.975, P=0.012), respectively. In study 3, serum Lp(a) levels were negatively correlated with MASLD (OR=0.885, 95% CI 0.746-0.980, P=0.025). Notably, restricted cubic spline analysis revealed a significant linear dose-response relationship between serum Lp(a) levels and MASLD transitions. Conclusion: Serum Lp(a) levels are inversely associated with both the progression and regression of MASLD, indicating its potential role in reflecting disease dynamics.
Summary
Keywords
disease dynamics, Lipoprotein(a), Metabolic dysfunction-associated steatotic liver disease, progression, regression
Received
10 October 2025
Accepted
19 February 2026
Copyright
© 2026 Guo, Lin, Yu, Lu, Qin, Zhao, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Qun Zhang
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