在慢性乙型肝炎携带者核/潮类似物治疗后，肝脏和肝外部位

StephenW

J Clin Virol. 2017 Jul 5;94:8-14. doi: 10.1016/j.jcv.2017.06.009. [Epub ahead of print]
Compartmental HBV evolution and replication in liver and extrahepatic sites after nucleos/tide analogue therapy in chronic hepatitis B carriers.Gao S1, Duan ZP2, Chen Y2, van der Meer F3, Lee SS4, Osiowy C5, van Marle G6, Coffin CS7.
Author information
1Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Beijing Youan Hospital, Capital Medical University, Beijing, China.2Beijing Youan Hospital, Capital Medical University, Beijing, China.3Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.4Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.5Bloodborne Pathogens and Hepatitis Laboratory of the National Microbiology Laboratory, Winnipeg, MB, Canada.6Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.7Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: [email protected].

AbstractBACKGROUND: Hepatitis B virus (HBV) variants are associated with nucleos/tide analogue (NA) response and liver disease but it is unknown whether NA influences extrahepatic HBV persistence.
OBJECTIVES: To investigate HBV replication and genetic evolution in hepatic and extrahepatic sites of chronic hepatitis B (CHB) before and after NA therapy.
STUDY DESIGN: A total of 13 paired plasma, peripheral blood mononuclear cells (PBMC), were collected from chronic HBV carriers at baseline and after a median 53 weeks NA therapy as well as liver biopsy (N=7 baseline, N=5 follow-up). HBV covalently closed circular DNA (cccDNA) and messenger (m) RNA in liver and PBMC were analyzed. HBV polymerase (P)/surface (S), basal core promoter (BCP)/pre-core (PC)/C gene clonal sequencing was done in plasma, peripheral blood mononuclear cells (PBMC), and liver.
RESULTS: Compare to baseline, at ∼53 weeks follow-up, there was no significant change in HBV cccDNA levels in liver (0.2-0.08 copies/hepatocyte, p>0.05) or in PBMC 0.003-0.02 copies/PBMC, p>0.05), and HBV mRNA remained detectable in both sites. At baseline, BCP variants were higher in PBMC vs. liver and plasma. After therapy, drug resistant (DR) and immune escape (IE) variants increased in liver but IE and PC variants were more frequent in PBMC. HBV P/S diversity was significantly higher in PBMC compared to plasma.
CONCLUSION: Continuous HBV replication occurs in liver and PBMC and shows compartmentalized evolution under selective pressure of potent NA therapy.

Copyright © 2017 Elsevier B.V. All rights reserved.

KEYWORDS: Antiviral; HBV covalently closed circular DNA (cccDNA); HBV quasispecies; Mutation; Peripheral blood mononuclear cell (PBMC)

PMID:28709006DOI:10.1016/j.jcv.2017.06.009

StephenW

J Clin Virol。 2017年7月5日; 94：8-14。 Doi：10.1016 / j.jcv.2017.06.009。 [提前印刷]
在慢性乙型肝炎携带者核/潮类似物治疗后，肝脏和肝外部位的HBV进化和复制。
高S1，段ZP2，陈Y2，范德梅尔F3，李SS4，Osiowy C5，van Marle G6，Coffin CS7。
作者信息

1
加拿大卡尔加里卡尔加里大学卡姆加里医学院胃肠病与肝病学系卡尔加里肝单位; Department of Microbiology，Immunology and Infectious Diseases，Cumming School of Medicine，University of Calgary，Calgary，AB，Canada;首都医科大学北京友安医院，北京，中国。
2
首都医科大学北京友安医院，北京，中国。
3
加拿大卡尔加里卡尔加里大学兽医学院生态与公共卫生系。
4
加拿大卡尔加里卡尔加里大学卡姆加里医学院胃肠病学和肝病学系卡尔加里肝病单位。
五
血液病原体和肝炎实验室国家微生物实验室，温尼伯，加拿大MB。
6
Department of Microbiology，Immunology and Infectious Diseases，Cumming School of Medicine，University of Calgary，Calgary，AB，Canada。
7
加拿大卡尔加里卡尔加里大学卡姆加里医学院胃肠病与肝病学系卡尔加里肝单位; Department of Microbiology，Immunology and Infectious Diseases，Cumming School of Medicine，University of Calgary，Calgary，AB，Canada。电子地址：[email protected]。

抽象
背景：

乙型肝炎病毒（HBV）变体与核型/潮汐类似物（NA）反应和肝脏疾病相关，但是NA是否规定肝外HBV持续性是未知的。
目的：

研究HBV治疗前后慢性乙型肝炎（CHB）肝和肝外部位HBV复制和遗传演变。
学习规划：

在基线和中位数53周NA方法以及肝活检（N = 7个基线，N = 5次随访）后，从慢性HBV携带者收集总共13个配对的血浆，外周血单核细胞（PBMC）。 （B），基础核心启动子（BCP）/预核心（PC）/ C基因克隆测序（BCP）/预核心（PC）/ C基因克隆测序在血浆，外周血单核细胞（PBMC）和肝脏。
结果：

与基线相比，在53周随访期间，肝脏中HBV cccDNA水平（0.2-0.08拷贝/肝细胞，p> 0.05）或PBMC中0.003-0.02拷贝/ PBMC均无显着变化，p> 0.05） HBV抗体在两个位点均可检测。在基线时，BCP变体在PBMC中与肝脏和血浆相比较高。治疗后，耐药（DR）和免疫逃逸（IE）变体在肝脏中增加，但IE和PC变体在PBMC中更为频繁。与血浆相比，PBMC中HBV P / S多样性显着高于PBMC。
结论：

在肝脏和PBMC中连续HBV复制，并在有效NA治疗的选择压力下显示分隔的进展。

版权所有©2017 Elsevier B.V.保留所有权利。
关键词：

抗病毒; HBV共价闭合环状DNA（cccDNA）; HBV准种突变;外周血单核细胞（PBMC）

结论：
28709006
DOI：
10.1016 / j.jcv.2017.06.009