title: [Evolution of hepatitis C virus quasispecies during natural disease progression of chronic hepatitis C and the clinical implications].
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.E-mail: xuyongmin2636@foxmail.com.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Xu
authors.forename: Haiping
authors.initials: H
authors.lastname: Duan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Feng
authors.forename: Lihua
authors.initials: L
authors.lastname: He
authors.forename: Yalin
authors.initials: Y
authors.lastname: Li
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xia
mesh_terms: D001483:Base Sequence; D018450:Disease Progression; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D019562:Viral Load