Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma

Background/Aims: The hepatitis C virus (HCV) genome consists of quasispecie s populations of heterogeneous variants, especially in the hypervariable re gion, To assess the profiles of viral quasispecies in HCV-related hepatocel lular carcinoma, we studied the viral population patterns in serum and live r tissues of 13 HCV-positive patients with hepatocellular carcinoma develop ed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). Methods: HCV genome heterogeneity was analyzed by polymerase chain reaction -mediated single-strand conformation polymorphism analysis, which showed mu ltiple DNA bands representing different hypervariable region sequences. Results: The HCV populations were different between tumorous and nontumorou s tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 withou t 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 comple xity of HCV quasispecies were found in hepatocellular carcinoma with or wit hout underlying cirrhosis, Comparison of the HCV quasispecies profiles in s erum and liver tissues showed a different distribution of HCV variants betw een these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both witho ut cirrhosis, the HCV population in serum was completely different from tha t found in the liver. Conclusions: These results suggest that the complexity of HCV populations i s influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease, The different quasispeci es patterns found in serum and liver may reflect different biological prope rties of circulating and intrahepatic HCV particles or the existence of ext rahepatic sites of replication.