title: Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio is linked to advanced non-alcoholic fatty liver disease lean patients.
abstract: OBJECTIVE
  A small but significant proportion of patients with normal body mass index show non-alcoholic fatty liver disease (NAFLD). Oxidized low-density lipoprotein (LDL) is a powerful immunogenic molecule, which causes oxidative stress and produces antibodies (oxLDL-ab). We aimed to analyze the role of oxLDL-ab on histological features in lean-NAFLD patients.
  
  
  METHODS
  Seventy-two biopsy-proven NAFLD patients were included. Lean patients showed body index mass of <30 kg/m(2) . Liver biopsies were assessed by one pathologist blinded to clinical data. Histological features were non-alcoholic steatohepatitis (NASH), steatosis, hepatocellular ballooning, and liver fibrosis. Metabolic and hepatic profiles were analyzed, and lipid-lowering medication was recorded. OxLDL-ab levels were measured by ELISA. OxLDL-ab-based lipid indexes analyzed: oxLDL-ab/total cholesterol ratio; oxLDL-ab/LDL-c ratio; oxLDL-ab/high-density lipoprotein cholesterol (HDL-c) ratio; and oxLDL-ab/oxLDL ratio.
  
  
  RESULTS
  Lean-NAFLD patients presented 26.5% (9/34) of NASH. OxLDL-ab/HDL-c ratio (r = 0.570; n = 34; P = 0.001) correlated with NAS score and was the only variable associated with NASH in the multivariate analysis [odds ratio, OR, 1.10 (95% confidence interval, CI: 1.01-1.21); P = 0.039]. Severe steatosis was present in 41.2% (14/34) of lean-NAFLD patients. OxLDL-ab/HDL-c ratio was higher in patients with grade-III steatosis (54.9 (37.3-124.6)) than those with grade II (37.1 (20.2-71.1)) and grade I (17.7 (13.1-22.8)) (P = 0.018). Hepatocellular ballooning was present in 20.6% (7/34) of lean-NAFLD patients, and OxLDL-ab/HDL-c ratio (OR 1.03 [95% CI: 1.01-1.05]; P = 0.050) was independently associated with histological features. OxLDL-ab/HDL-c ratio was higher in patients with advanced fibrosis (39.8 (22.9-121.6) vs 17.7 (13.9-30.9); P = 0.025), increasing gradually with the fibrosis stage (P = 0.042) and remained in the final multivariate model [OR 1.05 (95% CI: 1.00-1.11); P = 0.05]. However, in obese-NAFLD patients, oxLDL/HDL-c ratio was not associated with histological features.
  
  
  CONCLUSIONS
  Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio could represent an interesting biomarker associated with NASH, hepatocellular ballooning, and liver fibrosis, in lean patients. OxLDL-ab/HDL-c could play an important role for distinguishing patients with and without NAFLD complications.
authors.affiliation: Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain.|Instituto de Biomedicina de Sevilla, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ampuero
authors.affiliation: Valme University Hospital, Sevilla, Spain.
authors.forename: Isidora
authors.initials: I
authors.lastname: Ranchal
authors.affiliation: Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain.|Instituto de Biomedicina de Sevilla, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Gallego-Durán
authors.affiliation: Pathology Unit, Valme University Hospital, Sevilla, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pareja
authors.affiliation: Instituto de Biomedicina de Sevilla, Sevilla, Spain.|Valme University Hospital, Sevilla, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Del Campo
authors.affiliation: Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain.|Instituto de Biomedicina de Sevilla, Sevilla, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Pastor-Ramírez
authors.affiliation: Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain.|Instituto de Biomedicina de Sevilla, Sevilla, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Rico
authors.affiliation: Cardiology Unit, Valme University Hospital, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Picón
authors.affiliation: Cardiology Unit, Valme University Hospital, Sevilla, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Pastor
authors.affiliation: Liver Research Unit, Department of Gastroenterology, Santa Cristina University Hospital, Madrid, Spain.
authors.forename: Carmelo
authors.initials: C
authors.lastname: García-Monzón
authors.affiliation: Unit for the Medical Management of Digestive Diseases & CIBERehd, Virgen de la Victoria University Hospital, Biomedical Research Institute of Málaga - IBIMA, Málaga, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Andrade
authors.affiliation: Inter-Centre Unit of Digestive Diseases & CIBERehd. Virgen Macarena - Virgen del Rocío University Hospitals, University of Sevilla, Sevilla, Spain. mromerogomez@us.es.|Instituto de Biomedicina de Sevilla, Sevilla, Spain. mromerogomez@us.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
mesh_terms: D000328:Adult; D000886:Anthropometry / Q000379:methods; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000150:complications / Q000276:immunology; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013851:Thinness / Q000097:blood / Q000150:complications / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol
keywords: HDL; NASH; fibrosis; inflammation; oxLDL-ab; steatosis