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

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

Kento Imajo  1 , Hideyuki Hyogo  2 , Masato Yoneda  1 , Yasushi Honda  1 , Takaomi Kessoku  1 , Wataru Tomeno  1 , Yuji Ogawa  1 , Masataka Taguri  3 , Hironori Mawatari  1 , Yuichi Nozaki  1 , Koji Fujita  1 , Hiroyuki Kirikoshi  1 , Satoru Saito  1 , Yoshio Sumida  4 , Masafumi Ono  5 , Koichiro Wada  6 , Atsushi Nakajima  1 , Yuichiro Eguchi  7
Affiliations
Clinical Trial

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

Kento Imajo et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Relationship between LDL-MI, as determined by PAGE, and sdLDL concentrations, measured by HPLC, in 49 patients with NAFLD.
LDL-MI was significantly correlated with sdLDL concentrations (r = 0.843, P<0.001).
Figure 2
Figure 2. Effects of the lipid lowering drugs (A) ezetimibe, (B) fibrate, and (C) atorvastatin on LDL-MI in patients with NAFLD.
All data are expressed as the mean ± SD. Statistical significance was determined using Student's t-test.
Figure 3
Figure 3. LDL-MI in patients with various liver diseases including NAFLD.
LDL-MI was significantly higher in patients with NAFLD patients than in patients with with ALD, CH-C, CH-B, AIH and PBC. Shown are the interquartile ranges (boxes), medians (dots), and ranges (vertical lines).
Figure 4
Figure 4. Mechanisms of increased LDL-MI, an indicator of sdLDL, in patients with NASH.
Microsomal triglyceride transfer protein activity is much lower in the livers of patients with NASH than with NAFL, resulting in decreased synthesis of total VLDL and increased synthesis of TG-rich VLDL (VLDL1) , leading to an increase in sdLDL . The incidence of atherosclerotic diseases may therefore be quite high in patients with NASH.
See this image and copyright information in PMC

References

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