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

Abstract

Objective: Human fetuin/2HS-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. Design: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 one month.Methods: Serum AHSG was determined by radial immunodiffusion. Results:Compared to controls, significantly lower levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin, prothrombin was found.Febrile episodes were not associated with significantly decreased AHSG levels.Concentrations below 300 g/ml were associated with high mortality rate (52.0%, relative risk: 5.497, 95% C.I.: 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 patients is independent from all other variables that were found decreased in deceased patients. Conclusions: 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.

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

“…The protein is synthesized predominantly in the liver, and its serum level is decreased in patients with liver cirrhosis and hepatocellular cancer because of an impaired hepatic synthetic capacity. 25,26 The synthesis of human AHSG in the liver is downregulated by pro-inflammatory cytokines, indicating that this protein is a negative acute-phase reactant. 27 Estrogen might also influence the production of the protein, as suggested by the changes in its serum levels after menopause and estrogen therapy.…”

Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

“…AHSG is considered as a negative acute phase reactant, the concentration of which decreases during infections, trauma and liver cirrhosis (15)(16)(17). It is tempting to speculate on the biological significance of this protein in clinical settings where its concentration increases, i.e.…”

Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature

“…Studies in humans with severe liver damage such as cirrhosis (alcoholic liver cirrhosis, primary biliary cirrhosis), chronic hepatitis and cancer indicate that serum fetuin-A levels are decreased in such patients 5,31,32 . It may be the consequence of reduced fetuin-A synthesis by hepatocytes.…”

“…al postulated that acute phase response does not play the crucial role of fetuin-A concentrations in subjects with liver diseases because fetuin-A is not markedly reduced during febrile states or episodes of infections (sepsis or pneumonias) and its serum level is strongly correlated with prothrombin activity-the best indicator of protein synthetic liver function 32 . What is more, Kalabay et al proved that decreased serum fetuin-A level is a predictor of short-term mortality in patients with liver cirrhosis and hepatocellular cancer 32 . The situation is different in the case of diseases with fat accumulation in the liver, i.e.…”