Carotti Simone, Morini Sergio, Corradini Stefano Ginanni, Burza Maria Antonella, Molinaro Antonio, Carpino Guido, Merli Manuela, De Santis Adriano, Muda Andrea Onetti, Rossi Massimo, Attili Adolfo Francesco, Gaudio Eugenio
Department of Human Anatomy, University of Rome La Sapienza, Italy, Rome.
Liver Transpl. 2008 Jun;14(6):806-14. doi: 10.1002/lt.21436.
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.
活化的α-平滑肌肌动蛋白（α-SMA）阳性肝星状细胞（HSC）是慢性肝损伤中负责纤维化的周细胞。神经胶质纤维酸性蛋白（GFAP）通常由中枢神经系统中的星形胶质细胞表达，在体内肝脏的静止星状细胞亚群中也有表达。在大鼠中，已观察到损伤急性反应中GFAP表达增加，慢性反应中表达下调，而关于人类肝脏中GFAP表达的报道仍存在矛盾。我们研究了与α-SMA相比，GFAP作为慢性和移植后复发性丙型肝炎中早期活化HSC的免疫组织化学标志物的效用，并将GFAP表达与血管重塑和纤维化进展相关联。通过免疫组织化学和半定量评分系统，分析了来自尸体供体的正常肝脏活检组织[供体肝脏（DL）；n = 21]以及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）和丙型肝炎病毒肝硬化（HCV-C）患者（n = 16）肝脏中HSC中GFAP和α-SMA的表达以及微血管密度。与DL组相比，HCV-PTR、HCV-CH和HCV-C组中α-SMA阳性HSC的百分比显著更高（P < 0.01）。与DL组、HCV-C组（P < 0.01）和HCV-CH组（P < 0.05）相比，HCV-PTR组中GFAP阳性HSC的百分比显著更高，与DL组相比，HCV-CH组中GFAP阳性HSC的百分比也显著更高（P < 0.01），且与纤维化程度和微血管密度呈负相关（P < 0.01）。在HCV-PTR组中，GFAP阳性HSC的百分比与纤维化进展相关（P < 0.01）。总之，GFAP可能是HCV-CH中HSC早期活化的有用标志物，似乎可以预测HCV-PTR中的纤维化进展。
