Hu Zhong-jie, Lang Zhen-wei, Song Chen-zhao, Zhang Shi-jie
You'an Hospital, Beijing 100054, China.
Zhonghua Gan Zang Bing Za Zhi. 2003 Jul;11(7):394-7.
To identify hepatic progenitor cells (HPCs) in patients with severe hepatitis (SH) by detecting their markers and investigate the features of their distribution and location.
Liver tissues taken from 59 SH patients were tested for the receptor of stem cell factor (c-kit), pi-class glutathione S-transferase (GST-pi), cluster of differentiation 34 (CD34), cytokeratin 19 (CK19), cytokeratin 18 (CK18) and alpha fetoprotein (AFP) by immunohistochemistry (IHC). Meanwhile, 58 patients with acute or chronic hepatitis were also detected to act as controls.
Hepatic progenitor cells could be seen in SH patients. Most of them existed as ductular cells that had been called "typical ductular proliferation (ADP)" or "typical ductular reaction" in previous research. These ductular cells were mainly located at the portal areas, fibro septa, periportal parenchyma and the border of the pseudolobuli and inflammatory foci. Further, c-kit, GST-pi, CK19 and CK18, but not CD34 and AFP could be detected in these cells. Another kind of HPC was the small hepatocyte-like cell (SHLC), which could express c-kit, GST-pi, and CK18, but not CK19, CD34 and AFP. The semi-quantitative analysis showed that the scope of ADP in SH patients was significantly larger than that in acute and chronic hepatitis patients (chi2= 63.62, P<0.05), and the scope of ADP in subacute severe hepatitis and chronic severe hepatitis patients was also significantly larger than that in acute severe hepatitis patients.
In the course of regeneration of viral hepatitis, different types of pathology have different features. In acute and chronic hepatitis (G1-2), the regeneration is mainly owing to the proliferation of mature hepatocytes, and in chronic hepatitis (G3-4), there is the participation of HPCs, although they are limited. In severe hepatitis, however, since the replicative capacity of normal hepatocytes is impaired or prohibited, liver regenerates and restores mainly by the means of hepatic stem cells activation and proliferation. But the hepatic stem cells don't differentiate into their mature functional compartments directly at all. There are several intermediary or transition populations. In human severe hepatitis, they are mainly ductular cells, and parts of them are small hepatocyte-like cells.
通过检测肝祖细胞（HPCs）标志物来鉴定重型肝炎（SH）患者中的肝祖细胞，并研究其分布和定位特征。
采用免疫组织化学（IHC）法检测59例重型肝炎患者肝组织中的干细胞因子受体（c-kit）、π类谷胱甘肽S-转移酶（GST-π）、分化簇34（CD34）、细胞角蛋白19（CK19）、细胞角蛋白18（CK18）和甲胎蛋白（AFP）。同时，检测58例急性或慢性肝炎患者作为对照。
重型肝炎患者中可见肝祖细胞。其中大多数以导管样细胞形式存在，在以往研究中被称为“典型导管样增生（ADP）”或“典型导管样反应”。这些导管样细胞主要位于门管区、纤维间隔、汇管区周围实质以及假小叶与炎症灶的交界处。此外，在这些细胞中可检测到c-kit、GST-π、CK19和CK18，但未检测到CD34和AFP。另一种肝祖细胞是小肝细胞样细胞（SHLC），它可表达c-kit、GST-π和CK18，但不表达CK19、CD34和AFP。半定量分析显示，重型肝炎患者中ADP的范围明显大于急性和慢性肝炎患者（χ2 = 63.62，P < 0.05），亚急性重型肝炎和慢性重型肝炎患者中ADP的范围也明显大于急性重型肝炎患者。
在病毒性肝炎再生过程中，不同类型的病理变化具有不同特征。在急性和慢性肝炎（G1-2）中，再生主要归因于成熟肝细胞的增殖，而在慢性肝炎（G3-4）中，肝祖细胞参与其中，尽管数量有限。然而，在重型肝炎中，由于正常肝细胞的复制能力受损或被抑制，肝脏主要通过肝干细胞的激活和增殖来再生和恢复。但肝干细胞根本不会直接分化为成熟的功能区室。存在几个中间或过渡群体。在人类重型肝炎中，它们主要是导管样细胞，部分是小肝细胞样细胞。
