title: 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.
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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  UMIN000009614.
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.affiliation: Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kessoku
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sumida
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Pharmacology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Division of Hepatology, Saga Medical School, Liver Center, Saga, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Eguchi
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000209:etiology*; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism*; D011758:Pyrroles / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000069059:Atorvastatin; D000069438:Ezetimibe