Ribavirin induced hemolysis:A novel mechanism of action against chronic hepatitis C virus infection

作     者：Kaartik Soota Benedict Maliakkal 

作者机构：Department of Internal MedicineUnity Health SystemRochesterNY 14626United States Department of Gastroenterology and HepatologyUniversity of Rochester Medical CenterRochesterNY 14642United States 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2014年第20卷第43期

页      面：16184-16190页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100401[医学-流行病与卫生统计学] 10[医学] 

主　　题：Chronic hepatitis C Therapy Ribavirin Hemolysis He 

摘      要：Hepatitis C virus(HCV)is not usually cleared by our immune system,leading to the development of chronic hepatitis C *** HCV induces the production of various cytokines,predominantly by Kupffer cells(KCs),and creates a pro-inflammatory state in the *** chronic dysregulated production of interferon(IFN)and other cytokines by KCs also promotes innate immune ***(RBV)monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis *** virological response(SVR)is significantly higher when IFN is combined with RBV in chronic HCV(c HCV)***,the mechanism of their synergy remains *** theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system;however,these theories have serious *** propose that hemolysis,which universally occurs with RBV therapy and which is considered a limiting side effect,is precisely the mechanism by which the anti-HCV effect is *** hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance,leading to the synergy ofRBV with IFN-α.Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme,which is metabolized and detoxified by heme oxygenase-1(HMOX1)to carbon monoxide(CO),biliverdin and free iron(which induces ferritin).These metabolites of heme possess anti-inflammatory and antioxidant ***,HMOX1 plays an extremely important anti-oxidant,anti-inflammatory and cytoprotective role,particularly in KCs and ***1 has been noted to have anti-viral effects in hepatitis C infected cell ***,it has been shown to enhance the response to IFN-αby restoring interferon-stimulated genes(ISGs).This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN combination therapy for c HCV:(1)SVR rates are higher in pati