免疫耐受期具有基础核​​心启动子和/或前核心突变的乙型

StephenW

J Viral Hepat. 2020 May 8. doi: 10.1111/jvh.13315. [Epub ahead of print]
Clinical Features of Hepatitis B Patients at Immune-tolerance Phase with Basal Core Promoter and/or Precore Mutations.
Li MR1,2, Xu ZG2, Lu JH2, Zheng HW2, Ye LH2, Liu YY2, Liu ZQ2, Zhang HC2, Huang Y2, Dai EH2, Pan CQ3,4.
Author information

1
    Division of Infectious Disease, The First Affiliated Hospital of Jinan University, Guangzhou, China.
2
    Division of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, China.
3
    Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical Univerisity, Beijing, China.
4
    Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University School of Medicine, New York, NY, USA.

Abstract

Little data exists on basal core promoter/precore (BCP/PC) mutations in chronic hepatitis B (CHB) patients at the immune-tolerance (IT) phase. We studied consecutive treatment-naïve, CHBe-antigen (HBeAg) positive patients who had undergone liver biopsy and genotyping. Those in the IT phase or immune-clearance (IC) phase were enrolled for comparison of the frequency of BCP/PC mutations and their clinical presentations. Subgroup analyses for the IT group were also performed between patients with and without mutations, and IC patients between fibrosis stages≤2 vs fibrosis>2.Among 301 patients enrolled, 88/301 (29.24%) and 213/301 (70.76%) were at the IT and IC phase, respectively. The frequency of BCP/PC mutations in IT phase was significantly lower than those in IC phase (15.91% vs 64.79 %, P<0.001). The BCP mutation only was significantly more frequent than the PC mutation in both groups and also in all IC subgroups. IT patients with BCP/PC mutations had significantly higher quantitative anti-HBc levels compared with those of patients with wild-type virus (P<0.05). They also had significantly lower mean levels of alanine transaminase, aspartate transaminase, total bilirubin, and qAnti-HBc compared with those of IC patients (all P<0.05). Additionally, they were significantly younger in mean age; had higher platelet count, higher levels of HBV DNA and surface antigen, as well as higher frequency of genotype B than those of IC patients with fibrosis>2 (all P<0.05). BCP/PC mutations were found in IT patients with CHB. They had distinct clinical characteristics when compared with patients with wild-type or at IC phase. Further studies are needed to understand their natural history and treatment outcomes.

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KEYWORDS:

Hepatitis B virus; basal core promoter; hepatitis B e antigen; immune-tolerance; mutation; pre-core

PMID:
    32384194
DOI:
    10.1111/jvh.13315

StephenW

J病毒性肝炎。 2020年5月8日。doi：10.1111 / jvh.13315。 [Epub提前发布]
免疫耐受期具有基础核​​心启动子和/或前核心突变的乙型肝炎患者的临床特征。
Li MR1,2，Xu ZG2，Lu JH2，Zheng HW2，Ye LH2，Liu YY2，Liu ZQ2，Zhang HC2，Huang Y2，Dai EH2，Pan CQ3,4。
作者信息

1个
    暨南大学附属第一医院传染病科，广州。
2
    河北医科大学附属石家庄第五医院肝病科，石家庄
3
    首都医科大学附属北京地坛医院肝病研究中心，北京
4
    纽约大学医学院纽约大学朗格健康分校消化内科和肝病科，美国纽约。

抽象

关于慢性乙型肝炎（CHB）患者处于免疫耐受（IT）阶段的基础核心启动子/前核心（BCP / PC）突变的数据很少。我们研究了接受过肝活检和基因分型的连续治疗，未经治疗的CHBe抗原（HBeAg）阳性患者。纳入那些处于IT阶段或免疫清除（IC）阶段的患者，以比较BCP / PC突变的频率及其临床表现。还对有突变和无突变的患者之间进行了IT组的亚组分析，在纤维化分期≤2vs纤维化> 2的IC患者中，纳入301名患者，其中88/301名（29.24％）和213/301名（70.76％）分别在IT和IC阶段。 IT阶段BCP / PC突变的频率显着低于IC阶段（15.91％vs 64.79％，P <0.001）。在两组和所有IC亚组中，BCP突变仅比PC突变更为频繁。与野生型病毒患者相比，具有BCP / PC突变的IT患者具有更高的定量抗HBc水平（P <0.05）。与IC患者相比，他们的丙氨酸转氨酶，天冬氨酸转氨酶，总胆红素和qAnti-HBc的平均水平也显着降低（所有P <0.05）。此外，他们的平均年龄明显年轻。与具有纤维化> 2的IC患者相比，具有更高的血小板计数，更高的HBV DNA和表面抗原水平以及更高的B基因型频率（均P <0.05）。在患有CHB的IT患者中发现了BCP / PC突变。与野生型或IC期患者相比，它们具有独特的临床特征。需要进一步研究以了解其自然病史和治疗结果。

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关键字：

乙型肝炎病毒;基础核心启动子；乙型肝炎e抗原；免疫耐受突变;前核心

PMID：
    32384194
DOI：
    10.1111 / jvh.13315