The impact of elevation of total bilirubin level and etiology of the liver

30 The GlycoFibroTest and GlycoCirrhoTest are non-invasive alternatives for liver biopsy that can be 31 used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These 32 tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the 33 impact of etiology on the alteration of N-glycosylation and if other characteristics of liver patients 34 could have an influence on N-glycosylation. 35 In human liver patients, no specific alteration could be found to make a distinction according to 36 etiological factor, although alcoholic patients had a significant higher mean value for the 37 GlycoCirrhoTest. Undergalactosylation did not show a significantly different quantitative alteration 38 in the cirrhotic and non-cirrhotic population of all etiologies. Importantly, patients with an elevation 39 of total bilirubin level (>2 mg/dl) had a strong increase of glycans modified with α1-6 fucose. The 40 fucosylation-index was therefore significantly higher in fibrosis/cirrhosis and hepatocellular 41 carcinoma patients with elevated total bilirubin levels irrespective from etiology. Furthermore, in a 42 multiple linear regression analysis, only markers for cholestasis significantly correlated with the 43 fucosylation-index. 44 In mouse models of chronic liver disease, the fucosylation-index was uniquely significantly increased 45 in mice that were induced with a common bile duct ligation. Mice that were chronically injected with 46 CCl4 did not show this increase. Apart from this difference, common changes characteristic to 47 fibrosis development in mice were observed. Finally, mice induced with a partial portal vein ligation 48 did not show biological relevant changes indicating that portal hypertension does not contribute to 49 the alteration of N-glycosylation. 50