Quasispecies of hepatitis C virus and genetic drift of the hypervariable region in chronic type C hepatitis.

The sequential variations of amino acid sequences in the hypervariable region (HVR)-1 of hepatitis C virus (HCV) and changes of viremia in 2 patients with different clinicopathologic courses of chronic hepatitis C were studied. By using polymerase chain reaction amplification, cloning, and sequencing of HVR-1, genetic heterogeneity of HCV was shown. The highest annual rate of consensus amino acid variation per 100 sites in HVR-1 of a patient with acute exacerbation was 15.4 versus 2.3 in a patient without acute exacerbation. The serial serum HCV titers were also quantified. An abrupt elevation of serum titer was associated with acute exacerbation, whereas constant viremia was observed when acute exacerbation did not occur. These results show that a quasispecies of HCV exists and patients with different courses of chronic hepatitis may have different sequential changes in virus titer and genetic drift of HVR-1.