De Mitri M S, Mele L, Chen C H, Piccinini A, Chianese R, D'Errico A, Alberti A, Pisi E
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, Italy.
J Hepatol. 1998 Dec;29(6):887-92. doi: 10.1016/s0168-8278(98)80115-3.
BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively).
HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences.
The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver.
These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.
背景/目的：丙型肝炎病毒（HCV）基因组由异质变异体的准种群体组成，尤其是在高变区。为了评估HCV相关肝细胞癌中病毒准种的特征，我们研究了13例HCV阳性肝细胞癌患者血清和肝组织中的病毒群体模式，这些患者分别在肝硬化和非肝硬化肝脏上发生肝细胞癌（分别为5例和8例）。
通过聚合酶链反应介导的单链构象多态性分析来分析HCV基因组的异质性，该分析显示出代表不同高变区序列的多个DNA条带。
在3/5例肝硬化的肝细胞癌和6/8例非肝硬化的肝细胞癌中，肿瘤组织和非肿瘤组织中的HCV群体不同。除1例病例外，在所有病例的两个区域中均检测到至少一个或多个共同条带。在有或没有潜在肝硬化的肝细胞癌中，HCV准种的复杂性没有显著差异。血清和肝组织中HCV准种特征的比较显示，在6/7例患者中，这两个区域之间HCV变异体的分布不同。在4例病例中，检测到了共同序列和分区序列，而在2例非肝硬化病例中，血清中的HCV群体与肝脏中发现的完全不同。
这些结果表明，HCV群体的复杂性受肝细胞癌的存在影响，而非潜在慢性肝病的严重程度。血清和肝脏中发现的不同准种模式可能反映了循环和肝内HCV颗粒的不同生物学特性或肝外复制位点的存在。
