title: Sequence analysis of hepatitis C virus from patients with relapse after a sustained virological response: relapse or reinfection?
abstract: BACKGROUND
  A sustained virological response (SVR) is the major end point of therapy for chronic hepatitis C virus (HCV) infection. Late relapse of infection is rare and poorly characterized. Three of 103 patients with a SVR treated at the National Institutes of Health had late relapse. We evaluated HCV RNA sequences in serum and liver tissue to distinguish relapse from reinfection.
  
  
  METHODS
  Per patient, 10-22 clones of amplified 5' untranslated region were evaluated in pretreatment and relapse serum specimens and in liver biopsy specimens obtained during SVR. Genotypes and sequence diversity were evaluated. Four patients whose infection relapsed before they reached a SVR (ie, the early relapse group) were used as a comparison.
  
  
  RESULTS
  Results of tests for detection of serum HCV RNA in all patients with late relapse were repeatedly negative during the first 24 weeks after therapy but became positive 8, 75, and 78 months after SVR. Reinfection risk factors were absent in 2 of 3 patients. In all patients with early or late relapse, apart from minor variations, the original HCV sequence was present before treatment and after relapse. All liver biopsy specimens from patients with late relapse were HCV RNA positive at SVR, with sequences nearly identical to those of specimens obtained at other time points.
  
  
  CONCLUSIONS
  Sequence comparisons suggest that reappearance of HCV RNA years after a SVR can be from relapse of the initial viral infection rather than reinfection from a different virus.
authors.affiliation: Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Koji
authors.initials: K
authors.lastname: Hara
authors.forename: Maria M
authors.initials: MM
authors.lastname: Rivera
authors.forename: Christopher
authors.initials: C
authors.lastname: Koh
authors.forename: Mary
authors.initials: M
authors.lastname: Demino
authors.forename: Sandra
authors.initials: S
authors.lastname: Page
authors.forename: Pothu Raju
authors.initials: PR
authors.lastname: Nagabhyru
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
authors.forename: Theo
authors.initials: T
authors.lastname: Heller
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000821:virology; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012008:Recurrence; D016415:Sequence Alignment
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral
keywords: Hepatitis C virus; late relapse; liver; sequence