血清抗乙型肝炎核心蛋白抗体与停用核苷类似物治疗后的临

StephenW

Clin Gastroenterol Hepatol. 2018 Jun 11. pii: S1542-3565(18)30600-1. doi: 10.1016/j.cgh.2018.05.047. [Epub ahead of print]
Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated With Clinical Relapse After Discontinuation of Nucleos(t)ide Analogue Therapy.
Chi H1, Li Z2, Hansen BE3, Yu T2, Zhang X2, Sun J2, Hou J2, Janssen HLA4, Peng J5.
Author information

1
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
2
    Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
3
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Toronto Centre of Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
4
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Toronto Centre of Liver Disease, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: [email protected].
5
    Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: [email protected].

Abstract
BACKGROUND & AIMS:

Levels of antibodies against the hepatitis B virus (HBV) core protein (anti-HBc) have been associated with response to nucleos(t)ide analogue and (peg)interferon therapy in patients with chronic HBV infection. We performed a prospective study to determine whether the total serum level of anti-HBc level (immunoglobulins M and G) is associated with clinical relapse after discontinuation of nucleos(t)ide analogue-based therapy.
METHODS:

We collected data from patients with chronic HBV infection who discontinued nucleos(t)ide analogue therapy according to pre-specified stopping criteria, recruited from November 2012 through July 2016 at an academic hospital in Guangzhou, China. Patients were followed through February 2017. We performed comprehensive biochemical and virologic tests at every visit, and anti-HBc was quantified for 2 years after treatment cessation (at baseline and weeks 4, 8, 12, 24, 48, and 96). The primary endpoint was clinical relapse, defined as level of HBV DNA >2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal-these were also the criteria for retreatment.
RESULTS:

We followed 100 patients (71% positive for HB e antigen [HBeAg] at the start of nucleos(t)ide analogue therapy, 43% treated with entecavir or tenofovir) for a median of 2.5 years after stopping therapy. Clinical relapse occurred in 39 patients (in 46% of patients at year 4 after discontinuation). High level of anti-HBc at the end of treatment (hazard ratio [HR], 0.31 per log IU/mL; P=.002) and low level of HB surface antigen (HBsAg) at the end of treatment (HR, 1.71 per log IU/mL; P=.032) were associated with a reduced risk of clinical relapse after adjusting for age, start of nucleos(t)ide analogue therapy HBeAg-status, and consolidation therapy duration. At year 4, 21% of patients with anti-HBc levels at the end of treatment ≥1000 IU/mL developed a clinical relapse compared to 85% of patients with levels <100 IU/mL (P<.001). An HBsAg level at the end of treatment ≤100 IU/mL was associated with a reduced risk of relapse (HR 0.30; P=.045). However, 82% of patients had levels of HBsAg above 100 IU/mL; for these patients, level of anti-HBc at the end of treatment could be used to determine the risk of relapse (HR 0.39 per log IU/mL; P=.005).
CONCLUSION:

In a median 2.5-year follow-up study of patients with chronic HBV infection who stopped nucleos(t)ide analogue therapy, total serum level of anti-HBc at the end of treatment was associated with risk of clinical relapse. Serum level of anti-HBc might be used to select patients suitable for discontinuing nucleos(t)ide analogue therapy.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:

CHB; antiviral agents; prognostic factor; treatment cessation

PMID:
    29902645
DOI:
    10.1016/j.cgh.2018.05.047

StephenW

Clin Gastroenterol Hepatol。 2018年6月11日，pii：S1542-3565（18）30600-1。 doi：10.1016 / j.cgh.2018.05.047。 [电子版提前打印]
血清抗乙型肝炎核心蛋白抗体与停用核苷类似物治疗后的临床复发相关。
Chi H1，Li Z2，Hansen BE3，Yu T2，Zhang X2，Sun J2，Hou J2，Janssen HLA4，Peng J5。
作者信息

1
    荷兰鹿特丹鹿特丹Erasmus MC大学医学中心胃肠病学和肝病学系。
2
    广东省南方医科大学南方医院病毒性肝炎研究重点实验室传染病研究室。
3
    荷兰鹿特丹鹿特丹Erasmus MC大学医学中心胃肠病学和肝病学系;多伦多肝病中心，大学健康网络，多伦多综合医院，多伦多大学，加拿大安大略省多伦多。
4
    荷兰鹿特丹鹿特丹Erasmus MC大学医学中心胃肠病学和肝病学系;多伦多肝病中心，大学健康网络，多伦多综合医院，多伦多大学，加拿大安大略省多伦多。电子地址：[email protected]。
五
    广东省南方医科大学南方医院病毒性肝炎研究重点实验室传染病研究室。电子地址：[email protected]。

抽象
背景＆目标：

针对乙型肝炎病毒（HBV）核心蛋白（抗-HBc）的抗体水平与慢性HBV感染患者对核苷（三）酸类似物和（peg）干扰素治疗的反应相关。我们进行了一项前瞻性研究，以确定在停用基于核苷（酸）类似物的疗法后，抗-HBc水平的总血清水平（免疫球蛋白M和G）是否与临床复发相关。
方法：

我们从2012年11月至2016年7月在中国广州的一家学术医院招募的慢性HBV感染患者中，根据预先设定的停药标准停止了核苷（酸）类似物治疗。患者随访至2017年2月。我们在每次随访时进行全面的生化和病毒学检测，治疗停止后（基线时和第4,8,12,24,48和96周）对抗HBc进行量化2年。主要终点是临床复发，定义为HBV DNA水平> 2000 IU / mL，丙氨酸转氨酶水平超过正常上限的2倍 - 这些也是复治的标准。
结果：

我们随访了100例患者（核苷类似物治疗开始时HBeAg阳性71例阳性[HBeAg]，恩替卡韦或替诺福韦治疗43例）停止治疗后平均2.5年。 39例患者发生临床复发（停药后第4年46％的患者）。治疗结束时高水平的抗-HBc（危险比[HR]，0.31每log IU / mL; P = .002）和治疗结束时HB表面抗原（HBsAg）低水平（HR，1.71 log IU / mL; P = 0.032）与校正年龄，核苷（酸）类似物治疗HBeAg状态开始和巩固治疗持续时间后的临床复发风险降低相关。在第4年，治疗结束时抗-HBc水平≥1000IU / mL的患者中有21％发生临床复发，而<100 IU / mL水平的患者中有85％（P <.001）。治疗结束时HBsAg水平≤100IU / mL与复发风险降低有关（HR 0.30; P = 0.045）。但是，82％的患者HBsAg水平超过100 IU / mL;对于这些患者，治疗结束时抗-HBc水平可用于确定复发风险（HR为0.39 / log IU / mL; P = .005）。
结论：

在对停止核苷（酸）类似物治疗的慢性HBV感染患者进行的一项为期2.5年的随访研究中，治疗结束时抗-HBc总血清水平与临床复发风险相关。血清抗-HBc水平可用于选择适合停止核苷（酸）类似物治疗的患者。

版权所有©2018 AGA研究所。由Elsevier Inc.出版。保留所有权利。
关键词：

CHB;抗病毒药物;预后因素;治疗停止

结论：
    29902645
DOI：
    10.1016 / j.cgh.2018.05.047

Hepbest

不错。
停药4年后，46%的复发，需要重新抗病毒。也就是说54%的在停药4年后还是安全的。
当然，这个是否有肝损伤，就不清楚。
对于那些吃药副作用大，同时表抗低，核心抗体低的战友，是个选择。

另外，可以和这个一起看，停药后，宿主的免疫激活，表抗降低，得金牌
http://hbvhbv.info/forum/thread-1702061-1-1.html