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

3rd Department of Internal Medicine, Faculty of Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, Hungary.
European Journal of Gastroenterology & Hepatology (Impact Factor: 2.25). 04/2002; 14(4):389-94. DOI: 10.1097/00042737-200204000-00009
Source: PubMed


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.

10 Reads
  • Source
    • "At the population level, early detection influences national morbidity and mortality figures; at the individual level, this is ultimately a question of life and death. From a financial point of view, healthcare systems could also curb their expenses with early diagnosis provided the disease is detected early enough to widen the range of effective therapeutic options [1]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast and cervical cancers are both common malignancies in Hungarian women. The aim of this study was to evaluate the impact of nationwide screening programs on the incidence and mortality of breast and cervical cancers and to assess the role of primary care providers in this context. Published records from 2000-2011 on breast and cervical cancer screening activities in Hungary were reviewed. Previously unpublished data from the Hungarian National Cancer Registry were also included in this review. Hungarian outcomes were compared to international results. A nationwide screening program for breast cancer was established in Hungary in 2001. A similar program for cervical cancer was subsequently initiated in 2003. As of 2009, 50% of the population at risk took advantage of breast cancer screening, while the exact participation rate for cervical cancer screening could not be established due to deficiencies of reporting by private gynecologists. The Health Visitors Cervical Screening Program, a new initiative within the context of the nationwide cervical screening program, based on involvement of local primary care providers, had encouraging results which substantially raised participation rates. However, deficiencies were identified regarding flow of information between service providers, patients, and family physicians. There was a slight reduction in the incidence of breast cancer and a more pronounced reduction in the incidence of cervical cancer, as well as a reduction in mortality for both breast and cervical cancers associated with these screening initiatives. The inclusion of primary care providers may benefit nationwide screening programs by raising participation rates in the target population.
    European journal of gynaecological oncology 01/2013; 34(5):419-24. · 0.61 Impact Factor
  • Source
    • "81931, 13.7 mg/ml, in a final concentration of 84 μl/11.5 ml gel) recognizes the dipeptide form. The other type of antibody binding to the newly synthesized single chain form of fetuin-a, was raised by immunizing a rabbit with recombinant human protein (final concentration of 568 μl/11.5 ml gel) (Kalabay et al. 2002). Fasting serum samples were also used to examine standard clinical laboratory measurements, CRP, and homocysteine levels in the core laboratory of Semmelweis University (diagnostic instruments: D-Cell 5D—Diagon Ltd., Cobas Integra 400—Roche, STA-Compact—Diagnostica Stago). "
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been previously reported that serum levels of 70-kDa heat shock protein (Hsp70) are elevated in peripheral artery disease. The aim of the present study was to examine whether increased serum Hsp70 levels are related to the extent of arterial calcification and standard laboratory parameters of patients with peripheral artery disease, as well as to markers of inflammation (C-reactive protein), atherosclerosis (homocysteine), and calcification (fetuin-a). One hundred eighty chronic atherosclerotic patients with significant carotid stenosis and/or lower extremity vascular disease were enrolled in this cross-sectional study. Systemic atherosclerosis and calcification was assessed by ultrasound (carotid intima-media thickness (IMT), presence of calcification at the abdominal aorta, carotid and femoral bifurcations, and aortic and mitral cardiac valves). Standard serum markers of inflammation, diabetes, renal function, ankle-brachial indexes, and traditional risk factors for atherosclerosis were noted. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay. Standard laboratory parameters (clinical chemistry), C-reactive protein (CRP), and homocysteine levels were determined by an autoanalyzer using the manufacturer's kits. Fetuin-a levels were measured by radial immunodiffusion. Patients' median age was 64 (57-71) years, 69% were men, and 34.5% had diabetes. Serum heat shock protein 70 levels were significantly higher in patients with more severe arterial calcification (p < 0.02) and showed significant positive correlations with serum bilirubin (r = 0.23, p = 0.002) and homocysteine levels (r = 0.18, p = 0.02). Serum Hsp70 did not correlate with body mass index, IMT, CRP, or fetuin-a levels in this cohort. Logistic regression analysis confirmed the association between sHsp70 and calcification score (OR, 2.189; CI, 1.156-4.144, p = 0.016) and this correlation remained significant (OR, 2.264; CI, 1.021-5.020, p = 0.044) after the adjustment for age, sex, eGFR, smoking, CRP, and homocysteine levels. Our data show that serum Hsp70 levels correlate with the severity of atherosclerosis in patients with carotid artery disease and chronic lower limb ischemia. These data support a putative role for plasma Hsp70 in the development of arterial calcification. Nevertheless, further studies are required to investigate the usefulness of circulating Hsp70 level as a marker of atherosclerotic calcification.
    Cell Stress and Chaperones 11/2010; 16(3):257-65. DOI:10.1007/s12192-010-0237-3 · 3.16 Impact Factor
  • Source
    • "In the case of AHS, our data showed down-regulation of the protein in sera of both cohorts of EOCa and GOCa patients. The low concentration of AHS in ovarian carcinoma serum may be associated with depressed cellular immunity [38] and short-term mortality of patients similar to that reported for patients with liver cancer [39]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples. Enhanced expression of clusterin (CLU), alpha1-antitrypsin, haptoglobin and leucine rich glycoprotein was detected in all patients. However, the levels of alpha1-antichymotrypsin (ACT) was only enhanced in EOCa patients, while patients with GOCa were typically characterized by elevated levels of ceruloplasmin but lower levels of alpha2-HS glycoprotein. The enhanced expression of CLU in EOCa and GOCa patients and up-regulated expression of ACT specifically in EOCa patients were confirmed by ELISA. Immunohistochemical staining of biopsy samples of EOCa and GOCa patients demonstrated correlation of the acute-phase protein expression. Patients with EOCa and GOCa demonstrated distinctive aberrant expression of serum and tissue high abundance acute-phase proteins compared to negative control women.
    Proteome Science 07/2008; 6(1):20. DOI:10.1186/1477-5956-6-20 · 1.73 Impact Factor
Show more

Similar Publications