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乙型肝炎 e 抗原水平与聚乙二醇干扰素应答:前核心和基本核心启动子突变体的影响。

Hepatitis B e antigen levels and response to peginterferon: influence of precore and basal core promoter mutants.

机构信息

Departments of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

出版信息

Antiviral Res. 2013 Mar;97(3):312-7. doi: 10.1016/j.antiviral.2012.12.023. Epub 2012 Dec 26.

Abstract

Hepatitis B e antigen (HBeAg) levels may predict response to peginterferon (PEG-IFN) but are also influenced by presence of precore (PC) and core promoter (BCP) mutants. HBeAg was measured in 214 patients treated with PEG-IFN±lamivudine for 52weeks. Patients were classified at baseline as wildtype (WT) or non-WT (detectable PC/BCP mutants). Combined response (HBeAg loss with HBV DNA<2000IU/mL), HBeAg response (HBeAg loss with HBV DNA>2000IU/mL) or non-response was assessed at week78. Mean baseline HBeAg levels were 2.65logIU/mL in combined responders, 2.48 in non-responders and 2.24 in HBeAg responders (p=0.034). Baseline HBeAg levels were not associated with combined response after stratification by WT/non-WT. Within the PEG-IFN monotherapy group (n=104), patients with HBeAg<1logIU/mL at week24 had a higher probability of combined response (29% versus 12%, p=0.041). After stratification by WT/non-WT, WT patients with HBeAg<1logIU/mL at week24 had a probability of combined response of 78% (versus 19% in patients with >1logIU/mL, p<0.001), whereas no difference in response rates was observed in non-WT patients (p=0.848). The relationship between HBeAg levels and response to PEG-IFN depends upon the presence of PC/BCP mutants. HBeAg levels should therefore not be routinely used to select patients for PEG-IFN, nor for monitoring of therapy.

摘要

乙型肝炎 e 抗原 (HBeAg) 水平可能预测对聚乙二醇干扰素 (PEG-IFN) 的反应,但也受前核心 (PC) 和核心启动子 (BCP) 突变体的影响。对 214 例接受 PEG-IFN±拉米夫定治疗 52 周的患者进行了 HBeAg 检测。根据基线时是否存在野生型 (WT) 或非 WT (可检测到 PC/BCP 突变体),将患者分为两类。在第 78 周评估联合应答 (HBeAg 丢失和 HBV DNA<2000IU/mL)、HBeAg 应答 (HBeAg 丢失和 HBV DNA>2000IU/mL) 或无应答。联合应答者的基线 HBeAg 水平为 2.65logIU/mL,无应答者为 2.48logIU/mL,HBeAg 应答者为 2.24logIU/mL(p=0.034)。在按 WT/非 WT 分层后,基线 HBeAg 水平与联合应答无关。在 PEG-IFN 单药治疗组(n=104)中,第 24 周 HBeAg<1logIU/mL 的患者联合应答的可能性更高(29%对 12%,p=0.041)。按 WT/非 WT 分层后,第 24 周 HBeAg<1logIU/mL 的 WT 患者联合应答的概率为 78%(而 HBeAg>1logIU/mL 的患者为 19%,p<0.001),而非 WT 患者的应答率无差异(p=0.848)。HBeAg 水平与 PEG-IFN 反应之间的关系取决于 PC/BCP 突变体的存在。因此,HBeAg 水平不应常规用于选择 PEG-IFN 的患者,也不应用于监测治疗。

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