Sequence Analysis of the Hepatitis C Virus in Relapse after Sustained Virological Response: Relapse or Reinfection?

J Infect Dis. (2013) doi: 10.1093/infdis/jit541 First published online: October 14, 2013

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

+ Author Affiliations

Translational Hepatology Unit Liver Diseases Branch, National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Address Correspondence to: Theo Heller, MD, Liver Diseases Branch/NIDDK/NIH, Building 10, room 9B16, 10 Center Drive MSC 1800, Bethesda MD 20892-1800, Phone: 301 496 1721, Fax: 301 402 0491, Email: Theller@nih.gov

Abstract

Background. A sustained virological response (SVR) is the major endpoint of therapy of chronic HCV infection. Late relapse is rare and poorly characterized. Three of 103 SVR patients 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 to 22 clones of amplified 5'UTR were evaluated in pretreatment and relapse sera, and SVR liver biopsies. Genotypes and sequence diversity were evaluated. Four patients who relapsed prior to SVR were compared as early relapsers.

Results. Serum HCV RNA for the first 24 weeks post-therapy in all late relapsers were repeatedly negative, but became positive at 8, 75 and 78 months post SVR. Reinfection risk factors were absent in 2 of 3 patients. In all early and late relapsers, apart from minor variations, the original HCV sequence was present before treatment and after relapse. All late relapser liver biopsies were HCV RNA positive at SVR, with near-identical sequence to other time points.

Conclusion. Sequence comparisons suggest that reappearance of HCV RNA years after an SVR can be from relapse of the initial viral infection rather than reinfection from a different virus.

Received June 7, 2013.
Revision received July 9, 2013.
Accepted July 17, 2013.

Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013.

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