Abstract: Objective To investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition
in untreated patients with chronic hepatitis C. Methods Eleven patients chronic hepatitis C without previous specific anti-HCV
treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical
parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and
cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV
quasispecies during disease progression in relation to the major clinical parameters. Results A total of 631 HVR1 sequences
were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients
featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of
chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and
AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST
level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.
Conclusion Due to individual differences and immune pressure, HCV quasispecies can present with different patterns of
evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation
with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.