Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at w...Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.展开更多
Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and internatio...Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.展开更多
Objective To investigate the efficacy of polyethylene glycol(PEG).interferon a(PEG-IFNct)in treating HBeAg-positive chronic hepatitis B(CHB)and explore the
目的评估HBsAg水平变化对聚乙二醇干扰素(PEG-IFNα-2a)治疗HBeAg阴性慢性乙型肝炎疗效预测价值。方法 HBeAg阴性慢性乙型肝炎患者,采用PEG-IFNα-2a每次180μg,皮下注射,每周1次治疗,疗程48周。Architect HBsAg定量检测系统检测HBsAg,...目的评估HBsAg水平变化对聚乙二醇干扰素(PEG-IFNα-2a)治疗HBeAg阴性慢性乙型肝炎疗效预测价值。方法 HBeAg阴性慢性乙型肝炎患者,采用PEG-IFNα-2a每次180μg,皮下注射,每周1次治疗,疗程48周。Architect HBsAg定量检测系统检测HBsAg,实时荧光定量PCR法检测HBV DNA定量。以治疗24周时HBsAg下降1 lg IU/ml为临界点,比较高于临界点和低于临界点患者持续病毒学应答率差异,分别计算持续病毒学应答(SVR)的阳性预测值、阴性预测值和符合率。结果完成48周疗程61例。其中有43例(70.5%)在48周疗程结束时获得病毒学应答;随访24周,有23例(37.7%)患者获得SVR,20例复发。获得SVR患者HBsAg基线水平低于非SVR患者(P<0.05)。获得SVR患者在治疗24周时HBsAg下降幅度较复发及无应答患者显著(P<0.05)。治疗24周时HBsAg下降≥1 lg IU/ml对获得SVR的阳性预测值为95.5%,阴性预测值为94.9%,符合率为95.1%。结论对于应用PEG-IFNα-2a治疗的HBeAg阴性慢性乙型肝炎患者,治疗前HBsAg的水平以及治疗24周HBsAg的下降幅度是推断治疗应答状况的有效预测指标。展开更多
文摘Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.
基金Supported by National Key Research and Development Program of China 2023,No:2023YFC2308100.
文摘Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.
文摘Objective To investigate the efficacy of polyethylene glycol(PEG).interferon a(PEG-IFNct)in treating HBeAg-positive chronic hepatitis B(CHB)and explore the
文摘目的评估HBsAg水平变化对聚乙二醇干扰素(PEG-IFNα-2a)治疗HBeAg阴性慢性乙型肝炎疗效预测价值。方法 HBeAg阴性慢性乙型肝炎患者,采用PEG-IFNα-2a每次180μg,皮下注射,每周1次治疗,疗程48周。Architect HBsAg定量检测系统检测HBsAg,实时荧光定量PCR法检测HBV DNA定量。以治疗24周时HBsAg下降1 lg IU/ml为临界点,比较高于临界点和低于临界点患者持续病毒学应答率差异,分别计算持续病毒学应答(SVR)的阳性预测值、阴性预测值和符合率。结果完成48周疗程61例。其中有43例(70.5%)在48周疗程结束时获得病毒学应答;随访24周,有23例(37.7%)患者获得SVR,20例复发。获得SVR患者HBsAg基线水平低于非SVR患者(P<0.05)。获得SVR患者在治疗24周时HBsAg下降幅度较复发及无应答患者显著(P<0.05)。治疗24周时HBsAg下降≥1 lg IU/ml对获得SVR的阳性预测值为95.5%,阴性预测值为94.9%,符合率为95.1%。结论对于应用PEG-IFNα-2a治疗的HBeAg阴性慢性乙型肝炎患者,治疗前HBsAg的水平以及治疗24周HBsAg的下降幅度是推断治疗应答状况的有效预测指标。
