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联合使用乙型肝炎病毒抗原可预测核苷酸类似物/聚乙二醇干扰素序贯治疗的应答。

Combinational use of hepatitis B viral antigens predicts responses to nucleos(t)ide analogue/peg-interferon sequential therapy.

机构信息

Department of Medicine, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, 390-8621, Japan.

Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.

出版信息

J Gastroenterol. 2018 Feb;53(2):247-257. doi: 10.1007/s00535-017-1360-z. Epub 2017 Jun 20.

DOI:
10.1007/s00535-017-1360-z
PMID:28634723
Abstract

BACKGROUND

This prospective cohort study searched for factors associated with a response to nucleos(t)ide analogue/peg-interferon (NUC/peg-IFN) sequential therapy.

METHODS

A total of 95 patients with chronic hepatitis B being treated with NUCs were enrolled. Immediately following NUC cessation, peg-IFN was administered at 180 µg/dose weekly for 48 weeks.

RESULTS

Twenty-six patients (27%) were judged to be responders at 48 weeks after the completion of peg-IFN. Analysis of baseline factors revealed that hepatitis B surface antigen (HBsAg) <3.1 log IU/ml and HB core-related antigen (HBcrAg) <3.9 log U/ml were significant indicators of a treatment response. The levels of the markers decreased in both responders and non-responders during peg-IFN therapy but continued falling in responders only after halting peg-IFN. Lower HBsAg (<2.0 log IU/ml) and HBcrAg (<3.8 log U/ml) levels at the time of response judgment were also significantly associated with a favorable response. While lower HBcrAg at baseline was the sole predictor of decreased HBcrAg levels at judgment, lower HBsAg, lower HBcrAg, and the use of adefovir dipivoxil at baseline predicted decreased HBsAg levels at the study endpoint. The use of adefovir dipivoxil was also associated with higher serum IFN-λ3, which might have contributed to the reduction in patient HBsAg levels.

CONCLUSIONS

The combinational use of HBsAg and HBcrAg levels at baseline and their changes throughout sequential therapy may be useful for predicting a response to NUC/peg-IFN sequential therapy.

摘要

背景

本前瞻性队列研究旨在寻找与核苷(酸)类似物/聚乙二醇干扰素(NUC/peg-IFN)序贯治疗应答相关的因素。

方法

共纳入 95 例接受 NUC 治疗的慢性乙型肝炎患者。NUC 停药后,立即给予聚乙二醇干扰素 180μg/次,每周 1 次,共 48 周。

结果

48 周时,26 例(27%)患者被判定为应答者。对基线因素进行分析发现,乙肝表面抗原(HBsAg)<3.1logIU/ml和 HB 核心相关抗原(HBcrAg)<3.9logU/ml是治疗应答的显著指标。应答者和无应答者在聚乙二醇干扰素治疗期间标志物水平均下降,但仅在停止聚乙二醇干扰素后应答者继续下降。应答判断时较低的 HBsAg(<2.0logIU/ml)和 HBcrAg(<3.8logU/ml)水平也与良好的应答显著相关。虽然较低的 HBcrAg 是判断时 HBcrAg 水平降低的唯一预测因素,但较低的 HBsAg、HBcrAg 和基线时使用阿德福韦酯可预测研究终点时 HBsAg 水平降低。阿德福韦酯的使用还与较高的血清 IFN-λ3 相关,这可能有助于降低患者的 HBsAg 水平。

结论

基线时 HBsAg 和 HBcrAg 水平及其在序贯治疗过程中的变化联合使用,可能有助于预测 NUC/peg-IFN 序贯治疗的应答。

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Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection.核苷酸类似物而非核苷类似物的额外作用诱导IFN-λ3:乙肝病毒感染的一个新潜在靶点。
Gut. 2018 Feb;67(2):362-371. doi: 10.1136/gutjnl-2016-312653. Epub 2016 Oct 27.
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Baseline HBsAg and HBcrAg titres allow peginterferon-based 'precision medicine' in HBeAg-negative chronic hepatitis B patients.基线乙肝表面抗原(HBsAg)和乙肝核心相关抗原(HBcrAg)滴度有助于对e抗原阴性慢性乙型肝炎患者进行基于聚乙二醇干扰素的“精准医学”治疗。
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