Polzien, F.
(Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Gottingen, ,, Gottingen, Germany)
,
Ramadori, G.
Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade...
Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and ''classical'' cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and ''classical'' cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251-2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257-2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220-500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107-1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3-26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43-705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other ''classical'' cholestasis parameters. Increased sICAM-1 levels (range 257-2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3-19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33-1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110-1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264-919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than ''classical'' cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.
Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and ''classical'' cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and ''classical'' cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251-2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257-2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220-500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107-1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3-26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43-705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other ''classical'' cholestasis parameters. Increased sICAM-1 levels (range 257-2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3-19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33-1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110-1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264-919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than ''classical'' cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.
참고문헌 (36)
Dienstag 135 1984 Immunological mechanisms in chronic viral hepatitis
Hepatology Vallbracht 6 1308 1986 10.1002/hep.1840060614 Cell mediated cytotoxicity in hepatitis A virus infection
Eur J Immunol Dougherty 18 35 1988 10.1002/eji.1830180107 The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response
J Immunol Dustin 137 245 1986 10.4049/jimmunol.137.1.245 Induction by IL-1 and interferon-γ. Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1)
Hepatology Adams 14 426 1991 10.1002/hep.1840140305 Increased expression of ICAM-1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis
Clin Exp Immunol Thomson 95 83 1994 10.1111/j.1365-2249.1994.tb06019.x Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes
Gastroenterology Malizia 100 749 1991 10.1016/0016-5085(91)80021-Z Expression of leucocyte adhesion molecules in the liver of patients with chronic hepatitis-B virus infection
Hepatology Zöhrens 18 798 1993 10.1002/hep.1840180408 Intercellular adhesion molecule-1 concentration in sera of patients with acute and chronic liver disease: relationship to disease activity and cirrhosis
Gut Nouri-Aria 36 599 1995 10.1136/gut.36.4.599 Serum intercellular adhesion molecule-1 levels in chronic hepatitis C: association with disease activity and response to interferon a
Hepatology Manns 7 893 1987 10.1002/hep.1840070517 Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: identification and characterisation by radioimmunoassay and immunoblotting
Hepatology Beuers 15 603 1991 10.1002/hep.1840150409 Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease
Dig Dis Sci Mazzella 38 896 1993 10.1007/BF01295917 Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis
Hepatology Crosignani 14 1000 1991 10.1002/hep.1840140609 Changes in bile acid composition in patients with primary biliary cirrhosis induced by ursodeoxycholic acid administration
Ann Intern Med Fried 116 624 1992 10.7326/0003-4819-116-8-624 Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver
Gastroenterology Calmus 103 617 1992 10.1016/0016-5085(92)90855-S Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the mouse
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