乙型肝炎病毒引起的急性肝衰竭的临床结果和病毒基因组变

StephenW

Hepatology. 2018 Sep 19. doi: 10.1002/hep.30279. [Epub ahead of print]
Clinical outcome and viral genome variability of hepatitis B virus induced acute liver failure (HEP-18-0579).
Anastasiou OE1,2, Widera M1, Westhaus S1, Timmer L1, Korth J1, Gerken G2, Canbay A3, Todt D4, Steinmann E4, Schwarz T5, Timm J5, Verheyen J1, Ciesek S1.
Author information

1
    Institute of Virology, University Hospital of Essen, University of Duisburg, Essen, Germany.
2
    Department of Gastroenterology and Hepatology, University Hospital of Essen, Germany.
3
    Department of Gastroenterology and Hepatology, University Hospital of Magdeburg, Germany.
4
    Department of Molecular and Medical Virology, Ruhr University, Germany.
5
    Institute of Virology, University Hospital of Düsseldorf University of Düsseldorf, Germany.

Abstract
INTRODUCTION:

Acute hepatitis B virus (HBV) infection remains a frequent cause of acute liver failure (ALF) worldwide. ALF occurs in 0.1-0.5% of infected patients. Aim of this study was to scrutinize the outcome of patients with HBV induced ALF and mutational patterns of HBV variants, which might contribute to ALF.
METHODS:

From 2005 to 2016, 42 patients were treated for HBV-induced ALF in the University Hospital Essen, Germany. Clinical and virological data from these patients were collected. As a control, 38 patients with acute hepatitis B (AHB) without liver failure were included. The HBV genome was sequenced by Next Generation Sequencing (NGS). Mutations that were found by NGS were analyzed in vitro.
RESULTS:

8/42 patients had ALF without spontaneous recovery (NSR): 7 patients underwent liver transplantation (LTx) and one patient died before LTx. 34/42 patients (81%) had spontaneous recovery (SR) and cleared the infection, achieving either anti-HBs seroconversion or HBsAg loss. HBV genotype (GT)-D was the most frequent GT in ALF patients. Mutations in HBV core, preS2 and SHB (small hepatitis B surface antigen) were more frequent in patients with ALF -non spontaneous recovery (NSR) compared to ALF-spontaneous recovery (SR) or AHB patients. Amino acid deletions (16-22 and 20-22) in preS2 and SHB mutation L49R were exclusively detected in ALF-NSR patients. In vitro analyses reveal that these mutations did not influence HBsAg secretion or infectivity.
CONCLUSIONS:

HBV GT-D and increased variability in HBV core, preS2 region and SHB are associated with a worse clinical outcome of acute HBV infection. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HBV ; HLA ; NGS ; HBsAg; core protein

PMID:
    30229977
DOI:
    10.1002/hep.30279

StephenW

肝病。 2018年9月19日doi：10.1002 / hep.30279。 [提前打印]
乙型肝炎病毒引起的急性肝衰竭的临床结果和病毒基因组变异性（HEP-18-0579）。
Anastasiou OE1,2，Widera M1，Westhaus S1，Timmer L1，Korth J1，Gerken G2，Canbay A3，Todt D4，Steinmann E4，Schwarz T5，Timm J5，Verheyen J1，Ciesek S1。
作者信息

1
    德国埃森杜伊斯堡大学埃森大学医院病毒学研究所。
2
    德国埃森大学医院消化内科和肝脏病科。
3
    德国马格德堡大学医院消化内科和肝病学系。
4
    德国鲁尔大学分子与医学病毒学系。
五
    德国杜塞尔多夫杜塞尔多夫大学医学院病毒学研究所。

抽象
介绍：

急性乙型肝炎病毒（HBV）感染仍然是全世界急性肝衰竭（ALF）的常见原因。 ALF发生在0.1-0.5％的感染患者中。本研究的目的是仔细检查HBV诱导的ALF患者的结果和HBV变异的突变模式，这可能有助于ALF。
方法：

从2005年到2016年，42名患者在德国埃森大学医院接受了HBV诱导的ALF治疗。收集这些患者的临床和病毒学数据。作为对照，包括38例无肝功能衰竭的急性乙型肝炎（AHB）患者。通过下一代测序（NGS）对HBV基因组进行测序。在体外分析NGS发现的突变。
结果：

8/42例患者ALF无自发恢复（NSR）：7例患者接受肝移植（LTx），1例患者在LTx前死亡。 34/42例患者（81％）有自发恢复（SR）并清除感染，实现抗HBs血清转换或HBsAg消失。 HBV基因型（GT）-D是ALF患者中最常见的GT。与ALF-自发恢复（SR）或AHB患者相比，ALF-非自发恢复（NSR）患者中HBV核心，preS2和SHB（小乙肝表面抗原）的突变更常见。在ALF-NSR患者中专门检测到preS2和SHB突变L49R中的氨基酸缺失（16-22和20-22）。体外分析显示这些突变不影响HBsAg分泌或感染性。
结论：

HBV GT-D和HBV核心，preS2区域和SHB的变异性增加与急性HBV感染的较差临床结果相关。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

HBV; HLA; NGS;乙肝表面抗原;核心蛋白质

结论：
    30229977
DOI：
    10.1002 / hep.30279