title: Mutations in the NS5A gene are associated with response to interferon+ribavirin combination therapy in patients with chronic hepatitis C virus 3a infection.
abstract: BACKGROUND
  The clinical correlation between hepatitis C virus (HCV) NS5A gene mutations and response to antiviral treatment in HCV-3a-infected patients is not as well known as that in HCV-1a-infected and HCV-1b-infected patients.
  
  
  OBJECTIVE
  This study attempted to determine mutations in the NS5A gene in isolates of HCV-3a obtained from infected Pakistani patients treated with interferon-α standard therapy and to determine its association with several host factors.
  
  
  METHODS
  A total of 71 consecutive chronically infected HCV patients [43 men and 28 women, mean age 38 years (range, 16-70 years)] without previous antiviral therapy, who fulfilled other criteria of the current study were enrolled for antiviral therapy.
  
  
  RESULTS
  Of the 71 patients enrolled, 53 completed the course of antiviral therapy. Among them, 23 (43.3%) patients showed an end-of-treatment response, 20 (41.4%) showed a sustained virological response, and three (5.6%) patients were HCV-RNA negative at the end of treatment but developed a relapse thereafter. Only seven (13.2%) patients were virologic nonresponders (NR). Probable transmission risk factors were previous major/minor surgery (20%), transfusion of blood or blood products (2%), dental surgery (10%), or sporadic (unknown; 60%). The estimated duration of infection varied from 6 months to 20 years. The correlation between the number of mutations and several factors was also studied. The first factor that was associated with the number of mutations in the NS5A gene was age older than 40 years, where the difference was statistically significant between viral sequences of patients showing an end-of-treatment response and NR (P<0.001). Further, the difference in the average number of mutations was statistically significant between patients showing sustained virological response and NR (P<0.005). The second and third factors that were found to be associated with number of mutations in the NS5A gene were sex and viral load, respectively.
  
  
  CONCLUSIONS
  Along with host factors such as age older than 40 years, female sex, and low baseline viral load, the less number of mutations in the NS5A gene of HCV-3a is associated with a positive outcome of treatment response in HCV patients receiving interferon plus ribavirin therapy.
authors.affiliation: Division of Molecular Virology, Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ullah
authors.forename: Habib U
authors.initials: HU
authors.lastname: Rehman
authors.forename: Muhammad
authors.initials: M
authors.lastname: Idrees
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004252:DNA Mutational Analysis / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D012737:Sex Factors; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase