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聚乙二醇化干扰素α-2a治疗HBeAg阳性慢性乙型肝炎患者及对核苷类似物治疗部分病毒学应答的疗效

[Efficacy of pegylated-interferon alpha-2a treatment in patients with HBeAg-positive chronic hepatitis B and partial viral response to nucleoside analogue therapy].

作者信息

Li Ming-Hui, Hu Lei-Ping, Zhang Lu, Lu Yao, Shen Ge, Wu Shu-Ling, Chang Min, Mu Cai-Qin, Wu Yun-Zhong, Yang Min, Song Shu-Jing, Zhang Shu-Feng, Hua Wen-Hao, Xie Yao, Cheng Jun, Xu Dao-Zhen

机构信息

Medical Department 2 of Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2015 Nov;23(11):826-31. doi: 10.3760/cma.j.issn.1007-3418.2015.11.006.

Abstract

OBJECTIVE

To investigate the efficacy and related factors of pegylated-interferon alpha-2a (PEG-IFN-2a) treatment in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) who achieved partial viral response with nucleoside analogue (NA) therapy.

METHODS

Patients with HBeAg-positive CHB and partial viral response to NA treatment were administered a PEG-IFN-2a therapy regimen of 180 g subcutaneous injection once weekly for a personlized duration of time. The existing NA therapy was continued in combination with the new PEG-IFN-2a treatment for 12 weeks. Measurements of serum HBV DNA load, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg and hepatitis B e antibody (anti-HBe) were taken at baseline (prior to addition of the PEG-IFN-2a therapy) and every 3 months afterwards.For determining response to treatment, primary efficacy was defined as undetectable HBsAg and seroconversion, and secondary efficacy was defined as HBsAg less than 10 IU/mL and HBeAg seroconversion.Statistical analysis was carried out using SPSS statistical software.

RESULTS

A total of 81 consecutive patients with an average of 12.0 months (range: 6.0-24.0 months) of NA therapy were included in the study and received an average of 19.6 months (range: 15.5-33.3 months) of PEG-IFN-2a treatment. At the end of PEG-IFN-2a therapy, 7 (8.6%) of the patients achieved undetectable HBsAg and seroconversion, and 14 (17.3%) showed HBsAg less than 10IU/mL. In addition, 40.7% achieved undetectable HBeAg and seroconversion, a rate that was slightly higher than that (38.3%) seen in treatment-naive patients who received PEG-IFN-2a. Statistical analyses suggest that baseline level of HBsAg at less than 1500 IU/mL may predict end of PEG-IFN-2a treatment response for HBsAg less than 10 IU/mL, as evidenced by the area under the curve measure of 0.747, sensitivity measure of 87.3%, specificity measure of 33.3%, positive predictive value of 82.1% and negative predictive value of 42.8%.

CONCLUSION

Patients with HBeAg-positive CHB and partial viral response to NA therapy can achieve undetectable HBsAg and HBeAg seroconversion after switching to PEG-IFN-2a treatment. Baseline HBsAg level may be predictive of response to this therapeutic strategy.

摘要

目的

探讨聚乙二醇化干扰素α-2a(PEG-IFN-2a)治疗对核苷类似物(NA)治疗获得部分病毒学应答的乙肝e抗原(HBeAg)阳性慢性乙型肝炎(CHB)患者的疗效及相关因素。

方法

对HBeAg阳性CHB且对NA治疗有部分病毒学应答的患者给予皮下注射PEG-IFN-2a 180μg,每周1次,个体化治疗一段时间。继续原有的NA治疗并联合新的PEG-IFN-2a治疗12周。在基线(加用PEG-IFN-2a治疗前)及之后每3个月检测血清HBV DNA载量、乙肝表面抗原(HBsAg)、乙肝表面抗体(抗-HBs)、HBeAg和乙肝e抗体(抗-HBe)。为确定治疗反应,主要疗效定义为HBsAg检测不到且血清学转换,次要疗效定义为HBsAg低于10IU/mL且HBeAg血清学转换。使用SPSS统计软件进行统计分析。

结果

共纳入81例连续患者,平均接受NA治疗12.0个月(范围:6.0 - 24.0个月),平均接受PEG-IFN-2a治疗19.6个月(范围:15.5 - 33.3个月)。在PEG-IFN-2a治疗结束时,7例(8.6%)患者HBsAg检测不到且发生血清学转换,14例(17.3%)患者HBsAg低于10IU/mL。此外,40.7%的患者HBeAg检测不到且发生血清学转换,该比例略高于接受PEG-IFN-2a初治患者的比例(38.3%)。统计分析表明,基线HBsAg水平低于1500IU/mL可能预测PEG-IFN-2a治疗结束时HBsAg低于10IU/mL的反应,曲线下面积为0.747,敏感度为87.3%,特异度为33.3%,阳性预测值为82.1%,阴性预测值为42.8%。

结论

HBeAg阳性CHB且对NA治疗有部分病毒学应答的患者换用PEG-IFN-2a治疗后可实现HBsAg检测不到及HBeAg血清学转换。基线HBsAg水平可能预测该治疗策略的反应。

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