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World J Hepatol. Jan 18, 2016; 8(2): 123-130
Published online Jan 18, 2016. doi: 10.4254/wjh.v8.i2.123
Ribavirin: Past, present and future
Véronique Loustaud-Ratti, Marilyne Debette-Gratien, Jérémie Jacques, Sophie Alain, Pierre Marquet, Denis Sautereau, Annick Rousseau, Paul Carrier
Véronique Loustaud-Ratti, Marilyne Debette-Gratien, Jérémie Jacques, Denis Sautereau, Paul Carrier, Fédération Hépatologie, Service d’Hépato-gastroentérologie, CHU Limoges, 87042 Limoges, France
Véronique Loustaud-Ratti, Marilyne Debette-Gratien, Pierre Marquet, Annick Rousseau, Paul Carrier, Université de Limoges, UMR 850 INSERM, 87025 Limoges, France
Sophie Alain, Service de Bactériologie Virologie, CHU Limoges, 87042 Limoges, France
Sophie Alain, U1092 INSERM, Université de Limoges, CHU Limoges, 87042 Limoges, France
Pierre Marquet, Service de Pharmacologie, CHU Limoges, 87042 Limoges, France
Author contributions: Loustaud-Ratti V and Carrier P wrote the manuscript; Debette-Gratien M, Jacques J, Alain S, Marquet P, Sautereau D and Rousseau A read the manuscript and conducted a critical analysis.
Conflict-of-interest statement: The authors have no conflict of interest concerning this work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Véronique Loustaud-Ratti, Professor, Fédération Hépatologie, Service d’Hépato-gastroentérologie, CHU Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. veronique.loustaud-ratti@unilim.fr
Telephone: +33-5-55058484 Fax: +33-5-55056767
Received: September 2, 2015
Peer-review started: September 5, 2015
First decision: October 16, 2015
Revised: November 6, 2015
Accepted: December 29, 2015
Article in press: January 4, 2016
Published online: January 18, 2016
Processing time: 135 Days and 10.6 Hours
Abstract

Before the advent of direct acting antiviral agents (DAAs) ribavirin, associated to pegylated-interferon played a crucial role in the treatment of chronic hepatitis C, preventing relapses and breakthroughs. In the present era of new potent DAAs, a place is still devoted to the drug. Ribavirin associated with sofosbuvir alone is efficient in the treatment of most cases of G2 infected patients. All options currently available for the last difficult-to-treat cirrhotic G3 patients contain ribavirin. Reducing treatment duration to 12 wk in G1 or G4 cirrhotic compensated patients is feasible thanks to ribavirin. Retreating patients with acquired anti NS5A resistance-associated variants using ribavirin-based strategies could be useful. The addition of ribavirin with DAAs combinations however, leads to more frequent but mild adverse events especially in cirrhotic patients. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized even in difficult-to-treat patients: The optimization of ribavirin dosage according to an early monitoring of blood levels has been suggested to be relevant in double therapy with peginterferon or sofosbuvir but not with very potent combinations of more than two DAAs.

Keywords: Ribavirin; Hepatitis C; Peginterferon; Direct acting antiviral agents

Core tip: Ribavirin plays a crucial role when associated with peginterferon, preventing relapses and breakthroughs and doubling the support vector regression rate. Its antiviral effect is weak and ribavirin could enhance the response of interferon-stimulated genes in the combination. Ribavirin is still useful in the era of approved new direct acting antiviral agents (DAAs), in order to shorter treatment duration in genotype 1 or 4 cirrhotic patients, in all options available for genotype 3 cirrhotic patients, and as the only drug associated with sofosbuvir in genotype 2. Preliminary data with interferon-free second generation DAAs combinations without ribavirin suggest that future of the drug is jeopardized.