title: N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease is a spectrum of disorders ranging from steatosis to non-alcoholic steatohepatitis (NASH). Steatosis of the liver is benign, whereas NASH can progress to cirrhosis or even hepatocellular carcinoma. Currently, a liver biopsy is the only validated method to distinct NASH from steatosis.
  
  
  OBJECTIVE
  The objective of this study was to identify a biomarker specific for NASH based on the N-glycosylation of serum proteins.
  
  
  METHODS
  N-glycosylation patterns were assessed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis and compared with histology.
  
  
  RESULTS
  Initially, a glycomarker (log[NGA2F]/[NA2]) was developed based on the results obtained in 51 obese non-alcoholic patients scheduled for bariatric surgery. Multivariate analysis showed that our glycomarker had the lowest P-value of all biomarkers in distinguishing NASH from steatosis (P=0.069). The glycomarker was validated in a cohort of 224 non-alcoholic fatty liver disease patients. In both pilot and validation study, glycomarker score increased in ascending amount of lobular inflammation (single-factor ANOVA, P ≤ 0.001 and P=0.012, respectively). The N-glycan profile of immunoglobulin G in the NASH population confirmed the significantly increased undergalactosylation present in these patients.
  
  
  CONCLUSIONS
  Our glycomarker specifically recognises liver inflammation in obese individuals which is the main trigger for the development of steatohepatitis and can differentiate between steatosis and NASH.
authors: Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium. bram.blomme@ugent.be
authors: Bram
authors: B
authors: Blomme
authors: Sven
authors: S
authors: Francque
authors: Eric
authors: E
authors: Trépo
authors: Louis
authors: L
authors: Libbrecht
authors: Dieter
authors: D
authors: Vanderschaeghe
authors: An
authors: A
authors: Verrijken
authors: Piet
authors: P
authors: Pattyn
authors: Yves Van
authors: YV
authors: Nieuwenhove
authors: Dirk Van De
authors: DV
authors: Putte
authors: Anja
authors: A
authors: Geerts
authors: Isabelle
authors: I
authors: Colle
authors: Joris
authors: J
authors: Delanghe
authors: Christophe
authors: C
authors: Moreno
authors: Luc Van
authors: LV
authors: Gaal
authors: Nico
authors: N
authors: Callewaert
authors: Hans Van
authors: HV
authors: Vlierberghe
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D003937:Diagnosis, Differential; D019075:Electrophoresis, Capillary; D005234:Fatty Liver / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D054794:Glycomics; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000097:blood* / Q000150:complications; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G