Kojima S, Tanaka Y, Enomoto N, Marumo F, Sato C
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Liver. 1996 Feb;16(1):55-60. doi: 10.1111/j.1600-0676.1996.tb00704.x.
To investigate a cellular mode of HCV-infection in the liver and its pathological implications in relation to histopathological changes or clinical data, we studied the distribution of HCV-RNA in the livers of 21 patients with HCV-related chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases) using the in situ hybridization technique. In situ hybridization was performed on 4% paraformaldehyde-fixed frozen sections with digoxigenin-labeled DNA probe deduced from the core region of HC-J4. In situ hybridization showed positive signals in the liver specimens of 20/21 cases. The signals were localized in the cytoplasm of hepatocytes. The distribution pattern of positive cells was individually different, whereas the pattern was identical in the right and left lobes. There were no correlations of the HCV-positive cell number with serum aminotransferase levels at biopsy or with genotypes of HCV. The positive hepatocytes were occasionally associated with infiltrating mononuclear cells, and they were sparsely distributed in the area of piecemeal necrosis. These findings suggest that factors such as host immunoreaction to the virus may be more important than its direct cytopathy in the pathogenesis of chronic hepatitis C virus infection.
为了研究丙型肝炎病毒（HCV）在肝脏中的细胞感染模式及其与组织病理学变化或临床数据相关的病理意义，我们使用原位杂交技术研究了21例HCV相关慢性肝病患者（14例慢性活动性肝炎，7例肝硬化）肝脏中HCV-RNA的分布。用从HC-J4核心区域推导的地高辛标记DNA探针，对4%多聚甲醛固定的冰冻切片进行原位杂交。原位杂交显示21例中有20例肝脏标本呈阳性信号。信号定位于肝细胞的细胞质中。阳性细胞的分布模式个体不同，但左右叶的模式相同。活检时HCV阳性细胞数与血清转氨酶水平或HCV基因型之间无相关性。阳性肝细胞偶尔与浸润的单核细胞相关，且稀疏分布于桥接坏死区域。这些发现表明，在慢性丙型肝炎病毒感染的发病机制中，宿主对病毒的免疫反应等因素可能比其直接细胞病变更为重要。
