Persistent infection by hepatitis C virus is a major risk factor for the development of hepatocellular carcinoma, but the mechanism of hepatocarcinogenesis is unknown. To study the association of hepatitis C virus with hepatocellular carcinoma, we sequenced part of the 5' untranslated region of hepatitis C virus from the tumor tissue and the surrounding nontumorous liver of three patients with hepatocellular carcinoma. No sequence differences between tumor-derived and liver-derived hepatitis C virus isolates were detected. The conservation of the 5' untranslated region of hepatitis C virus-not only in infected hepatocytes, but also in neoplastic cellssuggests that the regulatory elements at the 5' terminus of the viral genome play an important role in the pathobiology of hepatitis C virus. (HEPATOLOGY 1994; 19551-553.) Hepatitis C virus (HCVI is a major pathogenic agent of chronic hepatitis which often leads to cirrhosis and HCC ( 1 ). The virus contains a positive-stranded RNA genome of approximately 9,400 nucleotides and presumably replicates through formation of negative-stranded RNA intermediates (2). Several complete sequences of HCV have been reported, revealing a single large translational open reading frame preceded at the 5' end by a relatively long untranslated region (5' UTR) ( 3 , 4). This 5' terminal region is 324 to 340 nucleotides long and represents the most highly conserved sequence among different HCV isolates (5 1. Recent studies suggest that the 5' UTR of HCV contains positive and negative translational control elements and may play a role in the pathobiology of chronic HCV infection ( 6 ) .
Many reports from around the world demonstrated a close association between chronic HCV infection and the development of HCC. The mechanism of malignant transformation, however, is not known. We and others recently demonstrated positive-stranded and negativestranded HCV RNA sequences. both in chronically