Human fetuin/alpha 2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer
ABSTRACT 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.
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ABSTRACT: This article describes a highly-sensitive surface plasmon resonance (SPR)-based immunoassay (IA) for human fetuin A (HFA), a specific biomarker for atherosclerosis and hepatocellular carcinoma. The assay is based on a novel immobilization procedure that simply involves the dilution of an anti-HFA capture antibody (Ab) in 1% (v/v) 3-aminopropyltriethoxysilane (APTES), followed by its dispensing on a KOH-treated gold (Au)-coated SPR chip and incubation for 30 min. The developed SPR IA detected 0.3-20 ng mL(-1) of HFA with a limit of detection and sensitivity of 0.7 ng mL(-1) and 1 ng mL(-1), respectively. The highly-simplified Ab immobilization procedure is also 5-fold more rapid than conventional procedures. It leads to the leach-proof binding of the capture Ab, which means that the developed SPR IA is highly cost-effective, as the Ab-bound SPR chip could be reused for many repeated HFA IAs after regeneration with 10 mM glycine-HCl, pH 2.0. The Ab-bound SPR chip, stored at 4 °C, lost only 18% of its original activity after 4 months. For the detection of HFA spiked in diluted human whole blood and plasma, the results obtained by the developed SPR IA agreed well with the commercial HFA sandwich ELISA.The Analyst 03/2014; 139(9). DOI:10.1039/c4an00149d · 3.91 Impact Factor
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ABSTRACT: A rapid sandwich enzyme-linked immunosorbent assay (ELISA)-based in vitro diagnostic (IVD) procedure has been developed for human fetuin A (HFA), an important disease biomarker for inflammatory diseases as well as malignancies. In this simplified and cost-effective procedure, the EDC-activated anti-HFA antibody (Ab) was admixed with 1% (v/v) 3-aminopropyltriethoxysilane (APTES) in 1:1 (v/v) and dispensed in a KOH-pretreated microtiter plate (MTP). APTES formed a stable complex with the capture antibody that was in turn covalently bonded on the KOH-treated surface in 30min. The resulting immunoassay (IA) format detects HFA with a dynamic range of 0.1-243ngmL(-1), and a limit of detection (LOD) and analytical sensitivity of 0.3ngmL(-1) and 1.0ngmL(-1), respectively. For the determination of HFA spiked in diluted human whole blood and serum, and HFA in ethylenediaminetetraacetic acid (EDTA)-plasma of patients, the obtained analytical precision is similar to that of the conventional sandwich ELISA. The anti-HFA Ab-bound MTPs, stored at 4°C in 0.1M PBS, pH 7.4, retained its biological activity for 8 weeks, thereby demonstrating excellent storage stability. This generic sandwich ELISA procedure can be extended for rapid, simplified and cost-effective detection of other disease biomarkers.Biosensors & Bioelectronics 07/2014; 67. DOI:10.1016/j.bios.2014.06.058 · 6.45 Impact Factor
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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.Advances in Medical Sciences 03/2014; 59(1):81-4. DOI:10.1016/j.advms.2013.08.003 · 0.80 Impact Factor