Viral loads and E2/NS1 region sequences of hepatitis C virus in hepatocellular carcinoma and surrounding liver.

Abstract

ObjectivesNumerous 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 been elucidated. We observed the changes of HCV in HCC to investigate the association of HCV with HCC.MethodsWe 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 two anti-HCV positive patients.ResultsThe copy numbers of HCV-RNA were 1×106 and 4×106/gm wet weight of HCC, and 8×107 and 3.2×108/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.ConclusionThese 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.