【摘要】 目的 在乙型肝炎病毒(HBV)所致的终末期肝病患者肝组织内，常可见大量的胆管增生，但其发生机制及临床意义尚不清楚。为阐明该类患者胆管增生的发生机制及其与卵圆细胞增生及肝细胞再生的关系，我们对8例HBV相关的终末期肝病患者及2例正常人肝组织进行了免疫组化染色及图像分析。方法 肝组织连续切片后进行免疫组化染色，观察指标为细胞角蛋白CK7、CK8、CK18、CK19、OV6、增殖细胞核抗原(PCNA)、谷胱甘肽S转移酶(GSTπ)、白蛋白(ALB)及甲胎蛋白(AFP)。结果 在所有8例患者肝组织汇管区内均可见典型增生的胆管及非典型增生的胆管，且对CK7、CK8、CK9、CK19、OV6及PCNA染色呈阳性反应，但两种类型的胆管在染色强度上存在明显差异。一些非典型增生的胆管细胞表现出肝卵圆细胞的形态学及免疫组化特征。某些小型肝细胞样细胞在形态及免疫组化特征方面介于肝卵圆细胞及成熟肝细胞之间。结论 在HBV相关的终末期肝病患者肝组织内，胆管增生可能存在不同起源。某些非典型增生的胆管细胞实际上就是活化的肝卵圆细胞。非典型增生的胆管细胞与肝细胞再生密切相关。小型肝细胞样细胞可能是肝卵圆细胞与成熟肝细胞之间的中间过渡细胞。

    【关键词】 肝病；胆管增生；肝干细胞；免疫组织化学

    Ductular proliferation in patients with hepatitis B virus induced end-stage chronic liver disease

    CHEN Yao-kai,QIAN Yi-dan,WANG Yu-ming.

    Institute of Infectious Diseases,Southwest Hospital,Third Military Medical University,Chongqing 400038,China

    【Abstract】 Objective Ductular proliferation is frequently observed in the liver tissue sections of patients with end-stage chronic liver disease induced by hepatitis B virus (HBV),but its pathogenesis and significance remain unclear.In order to clarify the pathogenesis of ductular proliferation and its possible association with oval cell activation and hepatocyte regeneration,we performed immunohistochemical staining and image analysis of the ductular structures in the liver tissues from 8 patients with HBV-induced end-stage chronic liver disease and 2 healthy individuals.Methods The liver specimens were sectioned serially,and then cytokeratin (CK) 7,CK8,CK9,CK19,OV6,proliferating cell nuclear antigens (PCNA),glutathione-S-transferase,α-fetal protein and albumin were stained immunohistochemically.Results Typical type and atypical type of ductular proliferation were observed in the portal tracts of the liver tissues in all 8 patients.The proliferating ductular cells were positive for CK7,CK8,CK9,CK19,OV6 and PCNA staining,however,typical proliferating ductular cells differed significantly from atypical ones in the intensity and extent of staining.Some atypical ductular cells displayed the morphological and immunohistochemical characteristics of hepatic oval cells.Some small hepatocyte-like cells were between hepatic oval cells and mature hepatocytes morphometrically and immunohistochemically.Conclusion We conclude that the proliferating ductules in the liver of patients with HBV-related end-stage chronic liver disease may have different origins.Some atypical ductular cells are actually activated hepatic oval cells.Atypical ductular proliferation is related to hepatocyte regeneration and small hepatocyte-like cells may be intermediate transient cells between hepatic oval cells and mature heptocytes. ......