丙型肝炎病毒(hepatitis C virus,HCV)是引起丙型肝炎的病原体,感染后极易慢性化并导致肝纤维化、肝硬化甚至肝癌。随着直接抗病毒药物(direct-acting antiviral agents,DAA)类抗HCV药物不断发展,临床上用其治疗后持续病毒学应答率逐渐...丙型肝炎病毒(hepatitis C virus,HCV)是引起丙型肝炎的病原体,感染后极易慢性化并导致肝纤维化、肝硬化甚至肝癌。随着直接抗病毒药物(direct-acting antiviral agents,DAA)类抗HCV药物不断发展,临床上用其治疗后持续病毒学应答率逐渐提高,药品不良反应明显减少。但近年来,DAA类抗HCV药物在国外临床应用中出现了一些严重不良反应事件,因此美国食品药品管理局在这些药物的使用说明书中加入了黑框警告。国内今年已开始陆续上市了多个DAA类抗HCV药物,但尚未大规模应用。本文阐述了此类药物的黑框警告内容(包括引起严重皮肤反应、导致心动过缓、严重肝损伤和乙型肝炎病毒再激活)及其发生机制,并提出预防及解决措施,为我国临床合理用药提供参考。展开更多
AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enr...AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.展开更多
An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alp...An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.展开更多
Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective...Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NS5B polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design, potent and specific inhibitors of NS3 and NS5B have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NS5A are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.展开更多
文摘丙型肝炎病毒(hepatitis C virus,HCV)是引起丙型肝炎的病原体,感染后极易慢性化并导致肝纤维化、肝硬化甚至肝癌。随着直接抗病毒药物(direct-acting antiviral agents,DAA)类抗HCV药物不断发展,临床上用其治疗后持续病毒学应答率逐渐提高,药品不良反应明显减少。但近年来,DAA类抗HCV药物在国外临床应用中出现了一些严重不良反应事件,因此美国食品药品管理局在这些药物的使用说明书中加入了黑框警告。国内今年已开始陆续上市了多个DAA类抗HCV药物,但尚未大规模应用。本文阐述了此类药物的黑框警告内容(包括引起严重皮肤反应、导致心动过缓、严重肝损伤和乙型肝炎病毒再激活)及其发生机制,并提出预防及解决措施,为我国临床合理用药提供参考。
文摘AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.
基金supported by National Institutes of Health grants AI070827 and CA33266American Cancer Society grant RSG-09-076-01 and the UIC Walter Payton Center GUILD
文摘An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.
文摘Over 170 million people worldwide are infected with hepatitis C virus (HCV), a major cause of liver diseases. Current interferon-based therapy is of limited efficacy and has significant side effects and more effective and better tolerated therapies are urgently needed. HCV is a positive, single-stranded RNA virus with a 9.6 kb genome that encodes ten viral proteins. Among them, the NS3 protease and the NS5B polymerase are essential for viral replication and have been the main focus of drug discovery efforts. Aided by structure-based drug design, potent and specific inhibitors of NS3 and NS5B have been identified, some of which are in late stage clinical trials and may significantly improve current HCV treatment. Inhibitors of other viral targets such as NS5A are also being pursued. However, HCV is an RNA virus characterized by high replication and mutation rates and consequently, resistance emerges quickly in patients treated with specific antivirals as monotherapy. A complementary approach is to target host factors such as cyclophilins that are also essential for viral replication and may present a higher genetic barrier to resistance. Combinations of these inhibitors of different mechanism are likely to become the essential components of future HCV therapies in order to maximize antiviral efficacy and prevent the emergence of resistance.
