N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis

Blomme, Bram; Francque, Sven; Trépo, Eric; Libbrecht, Louis; Vanderschaeghe, Dieter; Verrijken, An; Pattyn, Piet; Van Nieuwenhove, Yves; Van De Putte, Dirk; Geerts, Anja; Colle, Isabelle; Delanghe, Joris; Moreno, Christophe; Van Gaal, Luc; Callewaert, Nico; Van Vlierberghe, Hans

doi:10.1016/j.dld.2011.10.015

« Previous Next »Digestive and Liver Disease
Volume 44, Issue 4 , Pages 315-322, April 2012

N-glycan based biomarker distinguishing non-alcoholic steatohepatitis from steatosis independently of fibrosis

Bram Blomme
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
- Corresponding author. Tel.: +32 9 332 53 01; fax: +32 9 332 49 84.
Sven Francque
- Department of Hepatology and Gastroenterology, Antwerp University Hospital, Antwerp, Belgium
Eric Trépo
- Department of Gastroenterology and Hepatopancreatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Louis Libbrecht
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
Dieter Vanderschaeghe
- Unit for Molecular Glycobiology, Department for Molecular Biomedical Research, VIB, Ghent University, Ghent, Belgium
An Verrijken
- Department of Endocrinology, Diabetology and Metabole Diseases, Antwerp University Hospital, Antwerp, Belgium
Piet Pattyn
- Department of Surgery, Ghent University Hospital, Ghent, Belgium
Yves Van Nieuwenhove
- Department of Surgery, Ghent University Hospital, Ghent, Belgium
Dirk Van De Putte
- Department of Surgery, Ghent University Hospital, Ghent, Belgium
Anja Geerts
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
Isabelle Colle
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
Joris Delanghe
- Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium
Christophe Moreno
- Department of Gastroenterology and Hepatopancreatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Luc Van Gaal
- Department of Endocrinology, Diabetology and Metabole Diseases, Antwerp University Hospital, Antwerp, Belgium
Nico Callewaert
- Unit for Molecular Glycobiology, Department for Molecular Biomedical Research, VIB, Ghent University, Ghent, Belgium
Hans Van Vlierberghe
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium

Received 19 May 2011; accepted 20 October 2011. published online 28 November 2011.

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.

Aim

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.

Conclusion

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.

Keywords: Capillary, Electrophoresis, Glycomics, Inflammation, Immunoglobulin G