丙型肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)引起的急性和慢性传染病,自1989年丙型肝炎病毒被发现命名至今,全世界有3.26亿HCV感染者,虽然丙肝没有疫苗可以防控,但因直接抗病毒药物(DAA)的出现,丙肝的治愈率得到极大的提高。本综...丙型肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)引起的急性和慢性传染病,自1989年丙型肝炎病毒被发现命名至今,全世界有3.26亿HCV感染者,虽然丙肝没有疫苗可以防控,但因直接抗病毒药物(DAA)的出现,丙肝的治愈率得到极大的提高。本综述旨在阐述DAA药物对感染HCV的各类人群的治疗进展。展开更多
慢性丙型肝炎病毒（hepatitis C virus,HCV）感染的标准治疗方案（standard of care,SOC）是聚乙二醇干扰素（peginterferon,Peg-IFN）联合利巴韦林（ribavirin,RBV）治疗,对基因1、4、5型HCV感染者疗程为48周,2、3型感染者疗程为24周,...慢性丙型肝炎病毒（hepatitis C virus,HCV）感染的标准治疗方案（standard of care,SOC）是聚乙二醇干扰素（peginterferon,Peg-IFN）联合利巴韦林（ribavirin,RBV）治疗,对基因1、4、5型HCV感染者疗程为48周,2、3型感染者疗程为24周,在基因1型HCV感染者,其持续病毒学应答率为40%～50%,展开更多
目的系统评价Boceprevir联合聚乙二醇干扰素α和利巴韦林治疗基因1型慢性丙型肝炎的疗效及安全性。方法应用计算机检索Medline、CENTRAL和EMBASE数据库中关于Boceprevir联合聚乙二醇干扰素和利巴韦林三联疗法与聚乙二醇干扰素联合利巴...目的系统评价Boceprevir联合聚乙二醇干扰素α和利巴韦林治疗基因1型慢性丙型肝炎的疗效及安全性。方法应用计算机检索Medline、CENTRAL和EMBASE数据库中关于Boceprevir联合聚乙二醇干扰素和利巴韦林三联疗法与聚乙二醇干扰素联合利巴韦林二联疗法治疗基因1型慢性丙型肝炎患者的随机对照试验(RCTs)。应用Rev Man 5.3软件进行Meta分析。主要结局指标为持续病毒学应答(SVR)、不良反应事件发生率,次要结局指标为快速病毒学应答(RVR)和复发率。结果纳入4个RCTs,共2211例患者。无论初治或经治患者,三联疗法均能显著提高患者SVR[初治患者:64.08%(737/1150)对42.20%(176/417),OR=0.34,95%CI(0.27,0.42),P<0.00001;经治患者:63.02%(288/457)对21.09%(31/147),OR=0.16,95%CI(0.10,0.24),P<0.00001];三联疗法复发率显著低于二联疗法[11.33%(115/1015)对24.00%(66/275),OR=2.69,95%CI(1.90,3.81),P<0.00001];在获得RVR方面,两组差异无统计学意义[72.11%(843/1169)对51.861%(265/511),OR=0.48,95%CI(0.13,1.78),P=0.28];三联疗法显示出了较高的严重贫血发生率[3.98%(64/1607)对1.46%(9/614),OR=0.33,95%CI(0.16,0.68),P=0.003]、严重不良反应发生率[10.45%(168/1607)对7.33%(45/614),OR=0.66,95%CI(0.48,0.90),P=0.01]和因不良反应事件导致停药的发生率[12.49%(109/873)对5.18%(13/251),OR=0.37,95%CI(0.20,0.67),P=0.001]。结论 Boceprevir联合聚乙二醇干扰素和利巴韦林能显著提高基因1型慢性丙型肝炎初治或经治患者的SVR,减少复发率,但可能增加了严重不良事件发生率。受纳入研究的数量限制,上述结论尚待开展更多高质量研究加以验证。展开更多
Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognize...Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.展开更多
Chronic hepatitis C virus (HCV) infection is usually asymp-tomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in c...Chronic hepatitis C virus (HCV) infection is usually asymp-tomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84% ) than in those with HCV genotype 1 (36% ). Adverse events led to dose modification in 37 (31% ) and discontinuation in 8 (7% ). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar bet ween children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus.展开更多
文摘丙型肝炎是由丙型肝炎病毒(hepatitis C virus,HCV)引起的急性和慢性传染病,自1989年丙型肝炎病毒被发现命名至今,全世界有3.26亿HCV感染者,虽然丙肝没有疫苗可以防控,但因直接抗病毒药物(DAA)的出现,丙肝的治愈率得到极大的提高。本综述旨在阐述DAA药物对感染HCV的各类人群的治疗进展。
文摘慢性丙型肝炎病毒（hepatitis C virus,HCV）感染的标准治疗方案（standard of care,SOC）是聚乙二醇干扰素（peginterferon,Peg-IFN）联合利巴韦林（ribavirin,RBV）治疗,对基因1、4、5型HCV感染者疗程为48周,2、3型感染者疗程为24周,在基因1型HCV感染者,其持续病毒学应答率为40%～50%,
文摘目的系统评价Boceprevir联合聚乙二醇干扰素α和利巴韦林治疗基因1型慢性丙型肝炎的疗效及安全性。方法应用计算机检索Medline、CENTRAL和EMBASE数据库中关于Boceprevir联合聚乙二醇干扰素和利巴韦林三联疗法与聚乙二醇干扰素联合利巴韦林二联疗法治疗基因1型慢性丙型肝炎患者的随机对照试验(RCTs)。应用Rev Man 5.3软件进行Meta分析。主要结局指标为持续病毒学应答(SVR)、不良反应事件发生率,次要结局指标为快速病毒学应答(RVR)和复发率。结果纳入4个RCTs,共2211例患者。无论初治或经治患者,三联疗法均能显著提高患者SVR[初治患者:64.08%(737/1150)对42.20%(176/417),OR=0.34,95%CI(0.27,0.42),P<0.00001;经治患者:63.02%(288/457)对21.09%(31/147),OR=0.16,95%CI(0.10,0.24),P<0.00001];三联疗法复发率显著低于二联疗法[11.33%(115/1015)对24.00%(66/275),OR=2.69,95%CI(1.90,3.81),P<0.00001];在获得RVR方面,两组差异无统计学意义[72.11%(843/1169)对51.861%(265/511),OR=0.48,95%CI(0.13,1.78),P=0.28];三联疗法显示出了较高的严重贫血发生率[3.98%(64/1607)对1.46%(9/614),OR=0.33,95%CI(0.16,0.68),P=0.003]、严重不良反应发生率[10.45%(168/1607)对7.33%(45/614),OR=0.66,95%CI(0.48,0.90),P=0.01]和因不良反应事件导致停药的发生率[12.49%(109/873)对5.18%(13/251),OR=0.37,95%CI(0.20,0.67),P=0.001]。结论 Boceprevir联合聚乙二醇干扰素和利巴韦林能显著提高基因1型慢性丙型肝炎初治或经治患者的SVR,减少复发率,但可能增加了严重不良事件发生率。受纳入研究的数量限制,上述结论尚待开展更多高质量研究加以验证。
文摘Nitazoxanide,the first thiazolide,was originally developed for the treatment of Cryptosporidium parvum.More recently,antiviral activity of nitazoxanide against hepatitis B virus(HBV)and hepatitis C virus was recognized in in vitro systems.These basic studies led to phaseⅡclinical trials that demonstrated the safety and efficacy of nitazoxanide in combination with peginterferon,with or without ribavirin,in the treatment of chronic hepatitis C genotype 4.The sustained virologic response rate was 79%and 80%in two studies,which was higher than the response rate of 50%with the standard of care with peginterferon plus ribavirin.In very preliminary studies of patients with chronic hepatitis B,nitazoxanide suppressed serum HBV DNA and led to loss of hepatitis B e antigen in the majority of patients and hepatitis B surface antigen in approximately a quarter of patients.Randomized controlled studies of naive and nonresponder patients with chronic hepatitis C genotype 1 are underway,new second generation and controlled release thiazolides are being developed,and future studies of patients with chronic hepatitis B are planned.
文摘Chronic hepatitis C virus (HCV) infection is usually asymp-tomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84% ) than in those with HCV genotype 1 (36% ). Adverse events led to dose modification in 37 (31% ) and discontinuation in 8 (7% ). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar bet ween children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus.
