Ribavirin: How does it work and is it still needed?

被引:7
作者
Bunchorntavakul C. [1 ,2 ]
Reddy K.R. [1 ,2 ]
机构
[1] Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, 2 Dulles
[2] Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
关键词
Direct Acting Anti-viral (DAA); Epoetin; Erythropoiesis-stimulating agent; Hemolysis; Hepatitis C Virus (HCV); IMPDH inhibitor; Interferon signaling pathway; ITPA gene; Mechanisms of action; Mutagenesis; Peginterferon-alfa; Pegylated interferon; Relapse; Ribavirin; Ribavirin-induced anemia; Sustained Virologic Response (SVR); Taribavirin; Treatment; Weight-based dosing;
D O I
10.1007/s11901-011-0102-6
中图分类号
学科分类号
摘要
Ribavirin is a synthetic guanosine analogue, which acts against hepatitis C virus (HCV) through several mechanisms that include 1) immune modulation; 2) inhibition of inosine monophosphate dehydrogenase 3) inhibition of RNA-dependent RNA polymerase; 4) induction of HCV mutagenesis; and 5) modulation of interferonstimulated gene expression. Addition of ribavirin to peginterferon-α substantially improves sustained virologic response (SVR) and decreases relapse rates. Ribavirin can be associated with hemolytic anemia. However, recent data suggest that SVR is not negatively impacted by treatmentinduce anemia. Notably, optimal dosing strategy and the proper management of anemia are crucial to achieve the best treatment outcome. Several advances have been made in the areas relevant to ribavirin, such as the discovery of inosine triphosphatase gene as a promising pharmacogenetic marker and a predictor of anemia, and the role for erythropoiesis-stimulating agent in the management of anemia related to ribavirin use. Recent observations indicate that ribavirin will remain as a critical component of HCV therapy, even in the context of direct acting antivirals. © Springer Science+Business Media, LLC 2011.
引用
收藏
页码:168 / 178
页数:10
相关论文
共 59 条
[1]  
Brok J., Gluud L.L., Gluud C., Ribavirin monotherapy for chronic hepatitis C, Cochrane Database Syst Rev, (2009)
[2]  
Schalm S.W., Hansen B.E., Chemello L., Bellobuono A., Brouwer J.T., Weiland O., Cavalletto L., Schvarcz R., Ideo G., Alberti A., Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers, Journal of Hepatology, 26, 5, pp. 961-966, (1997)
[3]  
Mchutchison J.G., Gordon S.C., Schiff E.R., Shiffman M.L., Lee W.M., Rustgi V.K., Goodman Z.D., Ling M.-H., Cort S., Albrecht J.K., Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C, New England Journal of Medicine, 339, 21, pp. 1485-1492, (1998)
[4]  
Poynard T., Marcellin P., Lee S.S., Niederau C., Minuk G.S., Ideo G., Bain V., Heathcote J., Zeuzem S., Trepo C., Albrecht J., Randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus, Lancet, 352, 9138, pp. 1426-1432, (1998)
[5]  
Manns M.P., McHutchison J.G., Gordon S.C., Rustgi V.K., Shiffman M., Reindollar R., Goodman Z.D., Koury K., Ling M.-H., Albrecht J.K., Peginterferon alfa-2b plus ribavirin compared with interferonalfa-2b plus ribavirin for initial treatment of chronic hepatitis C: A randomised trial, Lancet, 358, 9286, pp. 958-965, (2001)
[6]  
Fried M.W., Shiffman M.L., Reddy K.R., Et al., Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection, N Engl J Med., 347, pp. 975-982, (2002)
[7]  
Hadziyannis S.J., Sette Jr. H., Morgan T.R., Et al., Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose, Ann Intern Med., 140, pp. 346-355, (2004)
[8]  
Wade J.R., Snoeck E., Duff F., Lamb M., Jorga K., Pharmacokinetics of ribavirin in patients with hepatitis C virus, British Journal of Clinical Pharmacology, 62, 6, pp. 710-714, (2006)
[9]  
Reddy K.R., Nelson D.R., Zeuzem S., Ribavirin: Current role in the optimal clinical management of chronic hepatitis C, J Hepatol., 50, pp. 402-411, (2009)
[10]  
Herrmann E., Lee J.-H., Marinos G., Modi M., Zeuzem S., Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon, Hepatology, 37, 6, pp. 1351-1358, (2003)