LDL-migration index (LDL-MI), an indicator of small dense low-density lipoprotein (sdLDL), is higher in non-alcoholic steatohepatitis than in non-alcoholic fatty liver: a multicenter cross-sectional study

PLoS One. 2014 Dec 26;9(12):e115403. doi: 10.1371/journal.pone.0115403. eCollection 2014.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risks of atherosclerotic diseases, including cardiovascular disease. However, the difference in risk between patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) has not yet been determined. Accumulating evidence has shown that high amounts of small dense low-density lipoprotein (sdLDL) are closely associated with atherosclerotic diseases. This study investigated differences in risk factors for atherosclerotic diseases, especially LDL-migration index (LDL-MI), an indicator of sdLDL, between patients with NAFL and NASH.

Methods: LDL-MI was analyzed in a primary cohort of 156 patients with NAFLD, including 53 with NAFL and 103 with NASH, and a validation cohort of 69 patients with NAFLD, including 25 with NAFL and 44 with NASH.

Results: In the primary cohort, NASH was associated with elevated LDL-MI (p = 0.039). Multiple regression analysis showed that NASH and the non-use of lipid lowering medications were independently correlated with higher LDL-MI in all patients with NAFLD. Among patients not on lipid lowering medications, those with NASH had significantly higher LDL-MI than those with NAFL (p = 0.001). These findings were confirmed in a validation cohort, in that LDL-MI was significantly higher in patients with NASH than with NAFL (p = 0.043).

Conclusion: This study is the first to show that LDL-MI, an indicator of sdLDL, was higher in patients with NASH than with NAFL, suggesting that the risk of atherosclerotic diseases may be higher in NASH than NAFL. Patients with NASH should be followed closely, especially for the progression of liver pathology and atherosclerotic diseases.

Trial registration: UMIN000009614.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticholesteremic Agents / therapeutic use*
  • Atherosclerosis / etiology*
  • Atorvastatin
  • Azetidines / therapeutic use
  • Cross-Sectional Studies
  • Ezetimibe
  • Female
  • Heptanoic Acids / therapeutic use
  • Humans
  • Lipoproteins, LDL / metabolism*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Pyrroles / therapeutic use
  • Risk Factors

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Heptanoic Acids
  • Lipoproteins, LDL
  • Pyrroles
  • Atorvastatin
  • Ezetimibe

Associated data

  • JPRN/UMIN000009614

Grants and funding

Work in the authors' laboratory was supported by the program “Step A” from the Japan Science and Technology Agency (J.S.T.) and Kiban-B, Shingakujuturyouiki. In addition, the present work was supported in part by grants-in-aid from the Japanese Ministry of Health, Labour and Welfare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.