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Updated: May 6, 2026
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Sequence analysis of hepatitis C virus from patients with relapse after a sustained virological response: relapse or
Koji Hara1, Maria M Rivera, Christopher Koh
1Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Insights
Late relapse of hepatitis C virus (HCV) infection after sustained virological response (SVR) is rare. Viral sequencing suggests this late relapse stems from the original infection, not reinfection.
Area of Science:
- Hepatology
- Virology
- Infectious Diseases
Background:
- Sustained virological response (SVR) is the primary goal for chronic hepatitis C virus (HCV) treatment.
- Late relapse of HCV infection post-SVR is uncommon and not well-understood.
- Three out of 103 patients at NIH experienced late relapse after achieving SVR.
Purpose of the Study:
- To investigate the cause of late relapse in hepatitis C virus (HCV) infection after sustained virological response (SVR).
- To differentiate between viral relapse and reinfection using HCV RNA sequence analysis.
- To characterize the viral sequences in patients experiencing late relapse.
Main Methods:
- Analyzed 5' untranslated region HCV RNA sequences from serum and liver biopsy specimens.
- Evaluated 10-22 clones per patient from pretreatment, SVR, and relapse samples.
- Compared sequence diversity and genotypes between early and late relapse groups.
Main Results:
- Late relapse patients initially tested negative for HCV RNA post-therapy, with positive results appearing 8-78 months after SVR.
- Two of three late relapse patients lacked risk factors for reinfection.
- HCV RNA was detected in liver biopsies of late relapse patients during SVR, with sequences nearly identical to pretreatment and relapse samples.
- Original HCV sequences were largely preserved in both early and late relapse patients.
Conclusions:
- Sequence data strongly suggest that late reappearance of HCV RNA after SVR is due to relapse of the initial infection.
- The findings challenge the notion of reinfection as the cause of late viral resurgence.
- This study provides critical insights into the long-term behavior of hepatitis C virus post-treatment.
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.
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