A relationship between the evolution of hepatitis C virus variants, liver damage, and hepatocellular carcinoma in patients with hepatitis C viremia

To clarify the mechanism of Liver damage induced by hepatitis C virus (HCV) and to determine whether the damage is related to hepatocellular carcinoma (HCC), HCV RNA levels were measured serially, and HCV genome mutations wer e analyzed from serum of 274 Japanese patients with chronic HCV viremia dur ing 1993-1998, All patients had alanine aminotransferase (ALT) levels measu red during 1986-1998, Patients with consistently normal ALT levels had iden tical and highly conserved HCV core regions; however, those with consistent ly abnormal ALT levels had quasi species, and the population of the quasi s pecies changed over time, HCV RNA levels did not change in the 274 patients . HCC developed in 31% of 80 patients with consistently abnormal ALT levels and in 4% of 92 patients with intermittently abnormal ALT levels but never in 102 patients with ALT levels consistently normal during 1993-1998. In p atients with chronic HCV viremia, persistent liver damage plays an importan t role in the development of HCC.