Abstract
OBJECTIVES: Numerous epidemiologic data have documented that chronic infection by hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular carcinoma (HCC). But the molecular mechanism underlying these strong epidemiologic associations between HCV and HCC has not be elucidated. We observed the changes of HCV in HCC to investigate the association of HCV with HCC. METHODS: We used competitive and quantitative polymerase chain reaction and dideoxy-nucleotide chain termination method to compare HCV titers and sequences of the hypervariable region of E2/NS1 region of four isolates from the HCC and surrounding cirrhotic liver tissues in tow anti-HCV positive patients. RESULTS: The copy numbers of HCV-RNA were 1 x 10(6) and 4 x 10(6)/gm wet weight of HCC, and 8 x 10(7) and 3.2 x 10(8)/gm wet weight of cirrhotic liver tissues from patient-1 and -2. The sequence differences between HCV RNA in HCC and in cirrhotic liver were two and five nucleotides in patient-1 and in patient-2 respectively. The amino acid sequences were changed in one and two site in each patient. CONCLUSION: These findings may suggest the possible etiological role of HCV in carcinogenesis of HCC, but complete sequence analysis of HCV including multiple isolates in the same patient, should be performed in many cases.