Human fetuin/α2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer
Human fetuin/alpha2HS-glycoprotein (AHSG) is synthesized by hepatocytes. We intended to determine whether liver dysfunction or acute phase reaction is dominant in the regulation of its serum concentrations and to see if decreased AHGS levels are associated with short-term mortality. We determined the serum AHSG levels in patients with acute alcoholic, acute A, B, and Epstein-Barr virus hepatitis, alcoholic cirrhosis, and hepatocellular cancer and correlated them to conventional laboratory parameters of inflammation and liver function. Patients were followed for 1 month. Serum AHSG was determined by radial immunodiffusion. Compared to controls, significantly lower AHSG levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin and prothrombin was found. Febrile episodes were not associated with significantly decreased AHSG levels. Concentrations below 300 microg/ml were associated with high mortality rate (52.0%; relative risk, 5.497; 95% confidence interval, 2.472-12.23; P < 0.0001). Of all laboratory parameters studied serum AHSG levels showed the greatest difference between deceased and survived patients with cirrhosis and cancer. Moreover, other acute phase reactants did not differ significantly. The multiple logistic regression analysis indicated that the decrease of serum AHSG is independent of all other variables that were found decreased in deceased patients. Decreased serum AHSG concentration is due rather to hepatocellular dysfunction than the acute phase reaction and is an outstanding predictor of short-term mortality in patients with liver cirrhosis and liver cancer.
[Show abstract] [Hide abstract] ABSTRACT: A rapid sandwich immunoassay (IA) with enhanced signal response for human fetuin A (HFA) was developed by modifying the surface of a KOH-treated polystyrene microtiter plate (MTP) with agarose and 3-aminopropyltriethoxysilane (APTES). The agarose-APTES complex binds covalently to the hydroxyl moiety of the MTP plate to serve as a binding platform for bioconjugation of EDC-activated anti-HFA antibody (Ab) via carbodiimide coupling. The one-step kinetics-based sandwich enzyme-linked immunosorbent assay (ELISA) enabled the detection of HFA in 30min with a limit of detection (LOD) and a linear range of 0.02ngmL(-1) and 1-243ngmL(-1), respectively. It detected HFA spiked in diluted human whole blood and serum, and HFA in ethylenediaminetetraacetic acid (EDTA)-plasma of patients with high precision similar to that of conventional ELISA. The anti-HFA Ab-bound agarose-functionalized MTPs retained their functional activity after 6 weeks of storage in 0.1M PBS, pH 7.4 at 4°C. Copyright © 2015 Elsevier B.V. All rights reserved.0Comments 1Citation
- "This could be the rationale behind a drastic decrease in HFA concentrations in the presence of calcification precursors found in patients with cardiovascular diseases (CVD) [38,39], atherosclerosis  and patients on dialysis . Decreased HFA levels in serum are also observed in acute alcoholic hepatitis, chronic autoimmune hepatitis, fatty liver, alcoholic and primary biliary cirrhosis, and hepatocellular carcinoma . The selective HFA contribution in the NPs, with a high potential to promote inflammation as opposed to its anti-inflammatory function, is of major relevance. "
[Show abstract] [Hide abstract] ABSTRACT: All diseases including autoimmune diseases, chronic liver diseases and cancer are a serious health problem worldwide. The current gold standard to assess malignant changes in cells and structural liver damage is through a biopsy, which has several disadvantages. A non-invasive simple test to diagnose malignancy and liver pathology would be highly desirable. Protein glycosylation has drawn the attention of many researchers with an aim to achieve this goal. Glycosylation is the post-translational modification of many secreted proteins and it has been known for decades that structural changes in the glycan structures of serum proteins are an indication of carcinogenesis and liver damage. The aim of this paper is to give an overview of the altered protein glycosylation in different etiologies of liver diseases, autoimmune diseases, and cancer. Although individual carcinoma and liver diseases have their own specific markers, the same alteration seems to reappear continuously in all malignant transformation and liver diseases like hyperfucosylation, sialylation, increased branching and bisecting N-acetylglucosamine.0Comments 1Citation
- "For example, increased branching has been demonstrated in a-2-HS-glycoprotein (AHSG) in alcoholic liver cirrhosis . AHSG concentration decreases in liver diseases such as in patients with acute alcoholic hepatitis, chronic autoimmune hepatitis, fatty liver disease, alcoholic and primary biliary cirrhosis and hepatocellular cancer . Decreased AHSG concentration and reduced sialylation was observed in RA . "
[Show abstract] [Hide abstract] ABSTRACT: To assess the serum fetuin A concentration as a potential marker of subclinical atherosclerosis in obese children with NAFLD. A prospective analysis of 45 obese children initially diagnosed with liver pathology (elevated serum ALT activity and/or ultrasonographic liver brightness and/or hepatomegaly) was conducted. The diagnosis of NAFLD was established in the children with elevated serum ALT activity and liver steatosis on ultrasound examination. Viral hepatitis, autoimmune, metabolic liver diseases (Wilson disease, alpha-1-antitrypsin deficiency, cystic fibrosis) and drug and toxin-induced liver injury were excluded in all children. The degree of liver steatosis was graded according to Saverymuttu scale and the total liver lipids concentration was assessed using proton magnetic resonance spectroscopy ((1)H MRS). Serum fetuin A concentration was significantly higher in examined children compared to the control group (n=30) (p=0.00002). Higher serum fetuin A concentration was also observed in children with NAFLD (n=19) in comparison to the controls (p=0.000026). Additionally, higher BMI values, waist circumferences, ALT and GGT activity, intensity of liver steatosis on ultrasound and total concentration of lipids in the liver in (1)H MRS were found in children with NAFLD compared to the rest of the examined obese patients (n=26). There was not found any correlation of the investigated glycoprotein with any other assessed parameters both in children with NAFLD and obese children without NAFLD. Higher serum fetuin A concentration found in children with NAFLD compared to the control group support the hypothesis that atherosclerotic processes may develop faster in hepatopatic obese patients.0Comments 5Citations
- "On the contrary to data obtained in adults with NAFLD, patients who had acute liver diseases (e.g. alcoholic hepatitis, drug-induced hepatitis ) and autoimmune hepatitis, showed lower serum fetuin A concentration . Moreover, the tendency to decrease the serum fetuin A concentration was a reliable and sensitive indicator of mortality in the patients with alcoholic liver cirrhosis . "