Polzien F, Ramadori G
Department of Internal Medicine, University of Göttingen, Germany.
J Hepatol. 1996 Dec;25(6):877-86. doi: 10.1016/s0168-8278(96)80292-3.
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.
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), gamma-glutamyl-transpeptidase (gamma-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.
Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251-2620 micrograms/l; median 966 micrograms/l) as well as in patients with extrahepatic cholestasis (257-2961 micrograms/l; median 760 micrograms/l) compared to healthy controls (n = 12; 220-500 micrograms/l; median 318 micrograms/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 gamma-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 micrograms/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 micrograms/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), gamma-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 was detectable in bile fluid (264-919 micrograms/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.
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.
背景/目的：已知胆汁淤积性肝病原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）患者血清中可溶性细胞间黏附分子水平升高，且一直被认为这表明免疫系统被激活以及炎症过程的程度。在肝炎和胆汁淤积性疾病中，在胆管上皮细胞和肝细胞表面发现了黏附分子的表达。
研究了因胆总管结石导致的PBC肝内胆汁淤积患者（n = 42）和肝外胆汁淤积患者（n = 18）血清中sICAM - 1水平。比较了sICAM - 1水平与“经典”胆汁淤积参数，如碱性磷酸酶（ALP）、γ - 谷氨酰转肽酶（γ - GTP）和胆红素水平。此外，分析了熊去氧胆酸（UDCA）治疗前后sICAM - 1浓度和“经典”胆汁淤积参数。另外，在4例因胆总管结石导致胆汁淤积的患者的血清和胆汁中检测了sICAM - 1。使用市售ELISA系统测定血清以及（若可获取）胆汁中的可溶性ICAM - 1水平。采用Wilcoxon符号秩精确检验和Spearman秩相关检验进行统计学分析。通过受试者工作特征（ROC）曲线分析胆汁淤积参数和sICAM - 1浓度的敏感性和特异性。
与健康对照者（n = 12；220 - 500μg/l；中位数318μg/l）相比，PBC患者（范围251 - 2620μg/l；中位数966μg/l）以及肝外胆汁淤积患者（257 - 2961μg/l；中位数760μg/l）的血清sICAM - 1浓度在相似范围内升高。在PBC患者中，sICAM - 1水平与组织学I至IV期（p < 0.001）、ALP（范围107 - 1877 U/l；中位数545 U/l；r = 0.496，p = 0.0008）、胆红素（范围0.3 - 26mg/dl；中位数0.8mg/dl；r = 0.52；p < 0.0004）和γ - GTP水平（范围43 - 705 U/l；中位数221 U/l；r = 0.36；p = 0.02）显著相关。在PBC患者中，如果sICAM - 1水平高于840μg/l，则可以高敏感性（95%）和特异性（85%）预测组织学III或IV期（n = 21）。用UDCA治疗PBC患者后，sICAM - 1水平随其他“经典”胆汁淤积参数的下降而显著降低。肝外胆汁淤积中升高的sICAM - 1水平（范围257 - 2961，中位数745μg/l）也与胆红素血清浓度（r = 0.8；p < 0.01；范围0.3 - 19.7，中位数1.6mg/dl）、γ - GTP（r = 0.55；p = 0.03；范围33 - 1401，中位数179 U/l）和ALP（r = 0.61；p = 0.1；范围110 - 1378，中位数562 U/l）显著相关。在4例进行鼻胆管插管的肝外胆汁淤积患者的胆汁中可检测到sICAM - 1（264 - 919μg/l）。
发现sICAM - 1浓度区分PBC组织学I/II期和III/IV期的敏感性和特异性高于“经典”胆汁淤积参数。肝内和肝外胆汁淤积中血清sICAM - 1浓度升高以及在胆汁中检测到sICAM - 1可能表明sICAM - 1通过胆汁被清除。换句话说，胆汁淤积性肝病患者血清sICAM - 1水平升高不仅可能是由于合成增加，也可能是由于清除减少。
