Sequence analysis of hepatitis c virus from patients with relapse after a sustained virological response: Relapse or reinfection?

Koji Hara, Maria M. Rivera, Christopher Koh, Mary Demino, Sandra Page, Pothu Raju Nagabhyru, Barbara Rehermann, T. Jake Liang, Jay H. Hoofnagle, Theo Heller

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)38-45
Number of pages8
JournalJournal of Infectious Diseases
Issue number1
StatePublished - Jan 1 2014
Externally publishedYes


  • Hepatitis C virus
  • late relapse
  • liver
  • sequence

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy


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