The multifaceted functions of ribavirin: Antiviral, immunomodulator, or both?

Hepatology

Volumn 60, Issue 4, 2014, Pages 1126-1129

  Mondelli, Mario U ^a,b  

^a FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; PEGINTERFERON ALPHA; RIBAVIRIN; STAT1 PROTEIN; STAT4 PROTEIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; ANTIVIRUS AGENT; GAMMA INTERFERON; MACROGOL DERIVATIVE; PEGINTERFERON ALPHA2A; RECOMBINANT PROTEIN;

ADAPTIVE IMMUNITY; ADJUVANT THERAPY; ANTIVIRAL THERAPY; CD4+ T LYMPHOCYTE; CORRELATIONAL STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOKINE RESPONSE; CYTOTOXICITY; DRUG MECHANISM; EDITORIAL; EXHAUSTION; HEPATITIS B VIRUS; HEPATITIS C; HUMAN; IMMUNOMODULATION; IN VITRO STUDY; IN VIVO STUDY; INNATE IMMUNITY; LONG TERM EXPOSURE; MONOTHERAPY; NATURAL KILLER CELL; OUTCOME ASSESSMENT; PERIPHERAL BLOOD MONONUCLEAR CELL; PERSONAL EXPERIENCE; PILOT STUDY; PRIORITY JOURNAL; PROTEIN CONTENT; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); TH1 CELL; TREATMENT FAILURE; UPREGULATION; VIRUS REPLICATION; FEMALE; HEPACIVIRUS; MALE; METABOLISM;

ANTIVIRAL AGENTS; FEMALE; HEPACIVIRUS; HEPATITIS C; HUMANS; INTERFERON-ALPHA; INTERFERON-GAMMA; KILLER CELLS, NATURAL; MALE; POLYETHYLENE GLYCOLS; RECOMBINANT PROTEINS; RIBAVIRIN;

EID: 84927798710     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.27186     Document Type: Editorial

References (27)

1. Hall CB, Walsh EE, Hruska JF, Betts RF, Hall WJ. Ribavirin treatment of experimental respiratory syncytial viral infection. A controlled double-blind study in young adults. JAMA 1983;249:2666-2670.
2. Paeshuyse J, Dallmeier K, Neyts J. Ribavirin for the treatment of chronic hepatitis C virus infection: a review of the proposed mechanisms of action. Curr Opin Virol 2011;1:590-598.
3. Kamar N, Rostaing L, Izopet J. Hepatitis E virus infection. Semin Liver Dis 2013;33:62-70.
4. Crotty S, Maag D, Arnold JJ, Zhong W, Lau JY, Hong Z, et al. The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med 2000;6:1375-1379.
5. Reddy KR, Nelson DR, Zeuzem S. Ribavirin: current role in the optimal clinical management of chronic hepatitis C. J Hepatol 2009;50:402-411.
6. Poordad F, McCone J, Jr., Bacon BR, Bruno S, Manns MP, Sulkowski MS, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011;364:1195-1206.
7. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011;364:2405-2416.
8. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2013;368:1878-1887.
9. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, et al. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med 2014;370:211-221.
10. Pawlotsky JM, Dahari H, Neumann AU, Hezode C, Germanidis G, Lonjon I, et al. Antiviral action of ribavirin in chronic hepatitis C. Gastroenterology 2004;126:703-714.
11. Hultgren C, Milich DR, Weiland O, Sällberg M. The antiviral compound ribavirin modulates the T helper (Th) 1/Th 2 subset balance in hepatitis B and C virus specific immune responses. J General Virol 1998;79:2381-2391.
12. Langhans B, Nischalke HD, Arndt S, Braunschweiger I, Nattermann J, Sauerbruch T, Spengler U. Ribavirin exerts differential effects on functions of CD4+ Th1, Th2, and regulatory T cell clones in hepatitis C. PLoS One 2012;7:e42094.
13. Bergamini A, Bolacchi F, Cepparulo M, Demin F, Uccella I, Bongiovanni B, et al. Treatment with ribavirin and interferon-alpha reduces interferon-gamma expression in patients with chronic hepatitis C. Clin Exp Immunol 2001;123:459-464.
14. Rotman Y, Noureddin M, Feld JJ, Guedj J, Witthaus M, Han H, et al. Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C. Gut 2014;63:161-169.
15. Rijckborst V, ter Borg MJ, Cakaloglu Y, Ferenci P, Tabak F, Akdogan M, et al. A randomized trial of peginterferon alpha-2a with or without ribavirin for HBeAg-negative chronic hepatitis B. Am J Gastroenterol 2010;105:1762-1769.
16. Oliviero B, Varchetta S, Paudice E, Michelone G, Zaramella M, Mavilio D, et al. Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections. Gastroenterology 2009;137:1151-1160.
17. Ahlenstiel G, Titerence RH, Koh C, Edlich B, Feld JJ, Rotman Y, et al. Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferon-alfa-dependent manner. Gastroenterology 2010;138:325-335.
18. Miyagi T, Takehara T, Nishio K, Shimizu S, Kohga K, Li W, et al. Altered interferon-alpha-signaling in natural killer cells from patients with chronic hepatitis C virus infection. J Hepatol 2010;53:424-430.
19. Ahlenstiel G, Edlich B, Hogdal LJ, Rotman Y, Noureddin M, Feld JJ, et al. Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C. Gastroenterology 2011;141:1231-1239.
20. Oliviero B, Mele D, Degasperi E, Aghemo A, Cremonesi E, Rumi MG, et al. Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic hepatitis C virus infection. J Hepatol 2013;59:38-44.
21. Bozzano F, Picciotto A, Costa P, Marras F, Fazio V, Hirsch I, et al. Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment. Eur J Immunol 2011;41:2905-2914.
22. Varchetta S, Mele D, Mantovani S, Oliviero B, Cremonesi E, Ludovisi S, et al. Impaired intrahepatic natural killer cell cytotoxic function in chronic hepatitis C virus infection. 2012;56:841-849.
23. Werner JM, Serti E, Chepa-Lotrea X, Stoltzfus J, Ahlenstiel G, Noureddin M, et al. Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection. Hepatology 2014;60:1160-1169.
24. Mondelli MU, Varchetta S, Negro F. Hepatitis C. In: Gershwin ME, Vierling JM, Manns MP, eds. Liver Immunology. New York, NY: Springer; 2014:207-230.
25. Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Subramanian GM, et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology 2014;146:736-743.
26. Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2014;383:515-523.
27. Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, et al. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 2013;310:804-811.