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The impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and men

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Abstract
The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the impact of etiology on the alteration of N-glycosylation and whether other characteristics of liver patients could have an influence on N-glycosylation. In human liver patients, no specific alteration could be found to make a distinction according to etiological factor, although alcoholic patients had a significant higher mean value for the GlycoCirrhoTest. Undergalactosylation did not show a significantly different quantitative alteration in the cirrhotic and non-cirrhotic population of all etiologies. Importantly, patients with an elevation of total bilirubin level (>2 mg/dl) had a strong increase of glycans modified with alpha 1-6 fucose. The fucosylation index was therefore significantly higher in fibrosis/cirrhosis and hepatocellular carcinoma patients with elevated total bilirubin levels irrespective of etiology. Furthermore, in a multiple linear regression analysis, only markers for cholestasis significantly correlated with the fucosylation index. In mouse models of chronic liver disease, the fucosylation index was uniquely significantly increased in mice that were induced with a common bile duct ligation. Mice that were chronically injected with CCl4 did not show this increase. Apart from this difference, common changes characteristic to fibrosis development in mice were observed. Finally, mice induced with a partial portal vein ligation did not show biological relevant changes indicating that portal hypertension does not contribute to the alteration of N-glycosylation.
Keywords
N-glycosylation, biomarker, etiology, α1-6 fucose, total bilirubin, glycomics, ALPHA-1-6 FUCOSYL-TRANSFERASE, HUMAN HEPATOMA TISSUES, HEPATOCELLULAR-CARCINOMA, PROTEIN GLYCOMICS, CLINICAL-PRACTICE, BIOPSY, CIRRHOSIS, GLYCOPROTEINS, FETOPROTEIN, EXPRESSION

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Citation

Please use this url to cite or link to this publication:

Chicago
BLOMME, BRAM, Christophe Van Steenkiste, Jacques Vanhuysse, Isabelle Colle, Nico Callewaert, and Hans Van Vlierberghe. 2010. “The Impact of Elevation of Total Bilirubin Level and Etiology of the Liver Disease on Serum N-glycosylation Patterns in Mice and Men.” American Journal of Physiology-gastrointestinal and Liver Physiology 298 (5): G615–G624.
APA
BLOMME, BRAM, Van Steenkiste, C., Vanhuysse, J., Colle, I., Callewaert, N., & Van Vlierberghe, H. (2010). The impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and men. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 298(5), G615–G624.
Vancouver
1.
BLOMME B, Van Steenkiste C, Vanhuysse J, Colle I, Callewaert N, Van Vlierberghe H. The impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and men. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY. 2010;298(5):G615–G624.
MLA
BLOMME, BRAM, Christophe Van Steenkiste, Jacques Vanhuysse, et al. “The Impact of Elevation of Total Bilirubin Level and Etiology of the Liver Disease on Serum N-glycosylation Patterns in Mice and Men.” AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY 298.5 (2010): G615–G624. Print.
@article{844669,
  abstract     = {The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the impact of etiology on the alteration of N-glycosylation and whether other characteristics of liver patients could have an influence on N-glycosylation. In human liver patients, no specific alteration could be found to make a distinction according to etiological factor, although alcoholic patients had a significant higher mean value for the GlycoCirrhoTest. Undergalactosylation did not show a significantly different quantitative alteration in the cirrhotic and non-cirrhotic population of all etiologies. Importantly, patients with an elevation of total bilirubin level ({\textrangle}2 mg/dl) had a strong increase of glycans modified with alpha 1-6 fucose. The fucosylation index was therefore significantly higher in fibrosis/cirrhosis and hepatocellular carcinoma patients with elevated total bilirubin levels irrespective of etiology. Furthermore, in a multiple linear regression analysis, only markers for cholestasis significantly correlated with the fucosylation index. In mouse models of chronic liver disease, the fucosylation index was uniquely significantly increased in mice that were induced with a common bile duct ligation. Mice that were chronically injected with CCl4 did not show this increase. Apart from this difference, common changes characteristic to fibrosis development in mice were observed. Finally, mice induced with a partial portal vein ligation did not show biological relevant changes indicating that portal hypertension does not contribute to the alteration of N-glycosylation.},
  author       = {BLOMME, BRAM and Van Steenkiste, Christophe and Vanhuysse, Jacques  and Colle, Isabelle and Callewaert, Nico and Van Vlierberghe, Hans},
  issn         = {0193-1857},
  journal      = {AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY},
  keyword      = {N-glycosylation,biomarker,etiology,\ensuremath{\alpha}1-6 fucose,total bilirubin,glycomics,ALPHA-1-6 FUCOSYL-TRANSFERASE,HUMAN HEPATOMA TISSUES,HEPATOCELLULAR-CARCINOMA,PROTEIN GLYCOMICS,CLINICAL-PRACTICE,BIOPSY,CIRRHOSIS,GLYCOPROTEINS,FETOPROTEIN,EXPRESSION},
  language     = {eng},
  number       = {5},
  pages        = {G615--G624},
  title        = {The impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and men},
  url          = {http://dx.doi.org/10.1152/ajpgi.00414.2009},
  volume       = {298},
  year         = {2010},
}

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