Serum lipoprotein(a) levels are inversely associated with metabolic dysfunction-associated steatosis liver disease progression: two cross-sectional studies and a longitudinal study

TL;DR

Higher levels of a blood protein called Lp(a) are linked to slower progression of liver disease related to metabolic issues, suggesting it could help track disease changes.

Contribution

This study is the first to show a consistent inverse relationship between serum Lp(a) levels and MASLD progression across cross-sectional and longitudinal analyses.

Findings

Elevated Lp(a) levels were inversely correlated with liver fat and fibrosis severity in cross-sectional data.

Lower baseline Lp(a) levels predicted new-onset and non-regression of MASLD in longitudinal analysis.

A linear dose-response relationship between Lp(a) and MASLD transitions was confirmed using restricted cubic spline analysis.

Abstract

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.

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.

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.

Serum Lp(a) levels are inversely associated with both the progression and regression of MASLD, indicating its potential role in reflecting disease dynamics.

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