Late Relapse After Hepatitis C Virus Treatment Is Rare

Clin Infect Dis 2017 Jan 1; 64:44. Sarrazin C et al. -  Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies .

Of Interest
Articles in Press - Journal of Hepatology 
Hepatitis C “true” late relapse beyond 48 weeks of sustained virologic response after direct acting antiviral therapy

Thomas Klag, Julia Dietz, Christoph R. Werner, Julia M. Schwarz, Ulrich M. Lauer, Robert Beck, Nisar P. Malek, Christoph Sarrazin, Christoph P. Berg

DOI: http://dx.doi.org/10.1016/j.jhep.2017.01.002

Publication stage: In Press Corrected Proof

Published online: January 9, 2017

Article Summary Source - NEJM Journal Watch

Late Relapse After Hepatitis C Virus Treatment Is Rare

January 3, 2017
Neil M. Ampel, MD reviewing Sarrazin C et al. Clin Infect Dis 2017 Jan 1.
Few patients treated with a sofosbuvir-containing regimen for hepatitis C virus infection had late recurrent viremia, and most occurrences appeared to be reinfections.

Neil M. Ampel, MD
Use of direct antiviral agents (DAAs) for the treatment of hepatitis C virus (HCV) infection has been associated with sustained viral suppression by 12 weeks after therapy (SVR12) in >90% of patients. Because HCV infection does not confer full protective immunity, it is important to determine the frequency of recurrences after SVR12 is achieved and to distinguish between posttreatment relapse and reinfection.

To explore these issues, researchers in Germany, Russia, France, and the U.S. conducted an industry-supported study, examining samples from 11 phase III trials that used the NS5B inhibitor sofosbuvir, alone or in combination. To distinguish late relapse from reinfection, they conducted NS5B deep sequencing analysis, short-fragment NS5B population sequencing, and phylogenetic analyses.

Among 3004 patients, only 12 (0.4%) were found to have detectable HCV RNA by 24 weeks after SVR12. Deep genetic sequencing and phylogenetic analyses revealed that 5 of these 12 patients had HCV with minimal genetic changes in the NS5B sequence, suggesting that the recurrence was due to relapse. In the other 7, the sequences prior to and after DAA therapy were significantly unrelated, indicating reinfection.

Comment
This well-performed study indicates that absence of detectable HCV RNA by 12 weeks after DAA therapy is a good measure of SVR. It also demonstrates that most cases of recurrence are due to reinfection. Unfortunately, the tools needed to distinguish reinfection from relapse are not generally available to clinicians, suggesting the need for longer follow-up of patients after DAA therapy and better strategies to prevent reinfection.

Late Relapse Versus Hepatitis C Virus Reinfection in Patients With Sustained Virologic Response After Sofosbuvir-Based Therapies