Epidemiology
Lower Lp(a) tracks the onset and progression of fatty liver disease across three cohorts totalling over 36,000 people (Front Nutr 2026)
Original title: Serum lipoprotein(a) levels are inversely associated with metabolic dysfunction-associated steatosis liver disease progression: two cross-sectional studies and a longitudinal study
This study combined two cross-sectional analyses and one longitudinal analysis to test whether serum Lp(a) tracks with metabolic dysfunction-associated steatotic liver disease (MASLD). In 12,962 participants undergoing transient elastography, higher Lp(a) was inversely correlated with the severity of both hepatic steatosis and fibrosis. In a longitudinal cohort of 17,661 people with repeated abdominal ultrasonography, lower baseline Lp(a) independently predicted new-onset MASLD (HR 0.895, 95% CI 0.834-0.962, P < 0.001) and non-regression of existing MASLD (HR 0.889, 95% CI 0.811-0.975, P = 0.012). In 5,927 UK Biobank participants with MRI proton density fat fraction and Lp(a) testing, Lp(a) was again inversely associated with MASLD (OR 0.885, 95% CI 0.746-0.980, P = 0.025), with a significant linear dose-response relationship. Across three large, independent cohorts, low Lp(a) consistently marks both the development and the persistence of fatty liver disease, a direction opposite to its cardiovascular risk association that merits mechanistic follow-up.
Original 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 written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.