Glial fibrillary acidic protein as an early marker of hepatic stellate cell activation in chronic and posttransplant recurrent hepatitis C
Glial fibrillary acidic protein as an early marker of hepatic stellate cell activation in chronic and posttransplant recurrent hepatitis C
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DOI：
10.1002/lt.21436
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发表时间：
2008-06-01
影响因子：
4.6
通讯作者：
Gaudio, Eugenio
中科院分区：
文献类型：
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作者：
Carotti, Simone;Morini, Sergio;Gaudio, Eugenio
活化的α-平滑肌肌动蛋白（α-SMA）阳性肝星状细胞（HSC）是负责慢性肝损伤中纤维化的周细胞。胶质细胞酸性蛋白（GFAP）通常由中枢神经系统中的星形胶质细胞表达，在体内肝脏中以静止星状细胞亚群的形式表达。在大鼠中，已观察到在对损伤的急性反应中GFAP表达增加和在慢性反应中下调，而关于人肝脏中GFAP表达的报道仍然相互矛盾。我们研究了GFAP与alpha-SMA相比作为慢性和移植后复发性丙型肝炎中早期活化HSC的免疫组化标记物的实用性，以及GFAP表达与血管重塑和纤维化进展的相关性。采用免疫组织化学和半定量评分系统，分析了从尸体供体获得的正常肝脏活检组织中GFAP和α-SMA的表达以及微血管密度[供体肝脏（DL）; n = 21]和来自移植后丙型肝炎病毒复发性肝炎（HCV-PTR）患者（n = 19），丙型肝炎病毒慢性肝炎（HCV-CH）患者，（n = 12）和丙型肝炎病毒性肝硬化（HCV-C）患者（n = 16）。HCV-PTR组、HCV-CH组和HCV-C组的α-SMA阳性HSC百分比显著高于DL组（P < 0.01）。HCV-PTR组GFAP阳性HSC的百分比显著高于DL、HCV-C（P < 0.01）和HCV-CH（P < 0.05）组，HCV-CH组显著高于DL组（P < 0.01），与纤维化程度和微血管密度呈负相关（P < 0.01）。HCV-PTR组中GFAP阳性HSC的百分比与肝纤维化进展相关（P < 0.01）。总之，GFAP可以代表HCV-CH中HSC早期活化的有用标志物，并且似乎可以预测HCV-PTR中的纤维化进展。
Activated alpha-smooth muscle actin (alpha-SMA)-positive hepatic stellate cells (HSCs) are pericytes responsible for fibrosis in chronic liver injury. The glial fibrillary acidic protein (GFAP), commonly expressed by astrocytes in the central nervous system, is expressed in vivo in the liver in a subpopulation of quiescent stellate cells. In the rat, increased GFAP expression in the acute response to injury and down-regulation in the chronic response have been observed, whereas reports concerning GFAP expression in human liver are still conflicting. We investigated the utility of GFAP compared to alpha-SMA as an immunohistochemical marker of early activated HSCs in chronic and posttransplant recurrent hepatitis C and correlated GFAP expression with vascular remodeling and fibrosis progression. With immunohistochemistry and a semiquantitative scoring system, the expression of GFAP and alpha-SMA in HSCs and the microvessel density were analyzed in biopsies from normal livers obtained from cadaveric donors [donor liver (DL); n = 21] and from livers from posttransplant hepatitis C virus recurrent hepatitis (HCV-PTR) patients (n = 19), hepatitis C virus chronic hepatitis (HCV-CH) patients, (n = 12), and hepatitis C virus cirrhosis (HCV-C) patients (n = 16). The percentage of alpha-SMA-positive HSCs was significantly higher in the HCV-PTR, HCV-CH, and HCV-C groups compared to the DL group (P < 0.01). The percentage of GFAP-positive HSCs was significantly higher in the HCV-PTR group compared to the DL, HCV-C (P < 0.01), and HCV-CH (P < 0.05) groups and in the HCV-CH group compared to the DL group (P < 0.01), inversely correlating with the extent of fibrosis and microvessel density (P < 0.01). In the HCV-PTR group, the percentage of GFAP-positive HSCs correlated with fibrosis progression (P < 0.01). In conclusion, GFAP could represent a useful marker of early activation of HSCs in HCV-CH and seems to predict fibrosis progression in HCV-PTR.