title: Clinical implications of viral quasispecies heterogeneity in chronic hepatitis C.
abstract: To determine the clinical significance of viral quasispecies heterogeneity, 59 patients with chronic hepatitis C were studied using singlestranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1); of these, 48 were subsequently treated with interferon-alpha. The SSCP method was validated using clones of known nucleotide sequence. HVR1 was amplified in 54 of 59 (92%) patients. The median number of SSCP bands per sample was 6 (range: 2-12). Increased quasispecies heterogeneity correlated with the estimated duration of HCV infection (P < 0.05), parenteral-acquired HCV infection (vs. sporadic, P < 0.05), serum HCV RNA levels (P < 0.05), and HCV genotype 1 infection (P < 0.05), but not with age, serum AST, ALT, or Knodell score. Patients who had complete and sustained response to interferon-alpha (n = 11) had lower pre-treatment quasispecies heterogeneity compared to patients who had complete response with relapse (n = 18, P < 0.05) or no complete response (n = 16, P < 0.01). However, multivariate analysis revealed that HCV viremia was a stronger predictor of response to interferon-alpha. These findings indicate that the estimated duration of HCV carriage, serum HCV RNA levels, and HCV type 1 are important determinants for the evolution of HCV quasispecies heterogeneity; and that increased HCV quasispecies heterogeneity is another marker associated with a poor subsequent response to interferon-alpha.
authors.affiliation: Department of Medicine, University of Florida, Gainesville 32610, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: González-Peralta
authors.forename: K
authors.initials: K
authors.lastname: Qian
authors.forename: J Y
authors.initials: JY
authors.lastname: She
authors.forename: G L
authors.initials: GL
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Mizokami
authors.forename: J Y
authors.initials: JY
authors.lastname: Lau
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D018740:Genetic Heterogeneity; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000097:blood*; D015203:Reproducibility of Results; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus