HBsAg阴性慢性乙型肝炎患者停用核苷酸类似物的长期临床结果

StephenW

Long-term clinical outcome of HBeAg-negative chronic hepatitis B patients who discontinued nucleos(t)ide analogues
Spilios Manolakopoulos  1   2 , Hariklia Kranidioti  1 , Anastasia Kourikou  1 , Melanie-Maria Deutsch  1 , Christos Triantos  3 , Chrysostomos Tsolias  3 , Emanuel K Manesis  4 , Nicoletta Mathou  5 , Alexandra Alexopoulou  1 , Emilia Hadziyannis  1 , George Papatheodoridis  2
Affiliations
Affiliations

    1
    Liver-GI Unit, 2nd Academic Department of Internal Medicine, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    2
    Academic Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
    3
    Division of Gastroenterology, Department of Internal Medicine, Medical School, University of Patras, Athens, Greece.
    4
    Liver Unit, Euroclinic, Athens, Greece.
    5
    Department of Gastroenterology, "Konstantopoulio-Patission" General Hospital, Nea Ionia, Athens, Greece.

    PMID: 33373114 DOI: 10.1111/liv.14654

Abstract

Background & aims: Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg-negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg-negative CHB patients who discontinued NA therapy.

Methods: This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6 years. All patients had regular blood tests. Virological relapse was defined as HBV DNA > 2000 IU/mL or >20 000 IU/mL and biochemical relapse as ALT > ULN (40 IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir.

Results: Of the 57 patients, 29 remained without retreatment after median follow-up of 65 months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48 months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA < 2000 IU/mL and ALT < ULN were 73%, 60%, 52%, 52%, 47% and 37% respectively. All patients had virological and biochemical response after retreatment. No patient developed liver failure, hepatocellular carcinoma or death. Cumulative rates of HBsAg loss were 2%, 4%, 7%, 10% and 20% at 3, 6, 12, 24 and 36 months. HBsAg levels < 100 IU/mL at the end of NA treatment could predict HBsAg loss (P = .001).

Conclusions: Our study supports that NA therapy can be safely stopped in non-cirrhotic patients with HBeAg-negative CHB. Over a median follow-up of more than 5 years, half of the patients remained without retreatment with a substantial proportion of them achieving functional cure.

Keywords: HBsAg clearance; retreatment rates; treatment discontinuation; virological relapse.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

StephenW

HBsAg阴性慢性乙型肝炎患者停用核苷酸类似物的长期临床结果
Spilios Manolakopoulos 1 2，Hariklia Kranidioti 1，Anastasia Kourikou 1，Melanie-Maria Deutsch 1，Christos Triantos 3，Chrysostomos Tsolias 3，Emanuel K Manesis 4，Nicoletta Mathou 5，Alexandra Alexopoulou 1，Emilia Hadziyannis 1，George Papatheodor 2
隶属关系
隶属关系

    1个
    希腊雅典国立和卡波德斯第安大学希波勒总医院第二内科肝内科肝脏肝脏科。
    2
    希腊雅典国立和卡波德斯第安大学莱科总医院消化内科。
    3
    希腊雅典帕特雷大学医学院内科，消化内科。
    4
    肝脏部，Euroclinic，雅典，希腊。
    5
    希腊雅典爱奥尼亚州“康斯坦托普利奥-帕蒂森”综合医院消化内科。

    PMID：33373114 DOI：10.1111 / liv.14654

抽象

背景与目的：在HBeAg阴性慢性乙型肝炎（CHB）中，终止核苷酸类似物（NA）仍是有争议的问题。这项研究旨在解决停止NA治疗的HBeAg阴性CHB患者的结局。

方法：这项前瞻性研究包括57名非肝硬化HBeAg阴性的白种人CHB患者，他们在中位病毒学缓解6年后中止了NA治疗。所有患者均接受定期血液检查。病毒学复发定义为HBV DNA> 2000 IU / mL或> 20 000 IU / mL，生化复发定义为ALT> ULN（40 IU / mL）或> 2xULN。所有符合预治疗标准的患者均重新开始使用恩替卡韦或替诺福韦。

结果：在这57例患者中，有29例在中止治疗后的65个月（范围：36-87）中位随访后仍未接受治疗。在3、6、12、24、36和48个月时，再治疗的累积率分别为16％，20％，32％，35％，46％和50％，而HBV DNA <2000 IU / mL的患者比例ALT <ULN分别为73％，6​​0％，52％，52％，47％和37％。所有患者复治后均具有病毒学和生化反应。没有患者出现肝功能衰竭，肝细胞癌或死亡。在3、6、12、24和36个月时，HBsAg的累积流失率分别为2％，4％，7％，10％和20％。 NA治疗结束时HBsAg水平<100 IU / mL可以预测HBsAg丢失（P = .001）。

结论：我们的研究支持非HBeAg阴性CHB的非肝硬化患者可以安全地停止NA治疗。在超过5年的中位随访中，一半的患者没有进行再治疗，其中很大一部分达到了功能治愈。

关键词：HBsAg清除率；再治疗率；中止治疗；病毒学复发。

©2020 John Wiley＆Sons A / S。由John Wiley＆Sons Ltd.发布。