Ribavirin: How Does it Work and is it Still Needed?
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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 interferon-stimulated 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 treatment-induce 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.
KeywordsRibavirin Hepatitis C Virus (HCV) Treatment Sustained Virologic Response (SVR) Relapse Mechanisms of action IMPDH inhibitor Mutagenesis Ribavirin-induced anemia Hemolysis Pegylated interferon Peginterferon-alfa ITPA gene Taribavirin Interferon signaling pathway Weight-based dosing Direct Acting Anti-viral (DAA) Erythropoiesis-stimulating agent Epoetin
K. Rajender Reddy received grants from Merck, Roche, Vertex, Tiboec, BMS and Gilead. He has received payment for development of educational presentations from CME activites-ViralEd and Rush University, and has also received payment from the American Board of Internal Medicine, Gastroenterology, Uptodate, and the Chronic Liver Disease Foundation; Chalermrat Bunchorntavakul reported no potential conflicts of interest relevant to this article.
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