在HBeAg /抗HBe血清转换期间选择基因型-D感染儿童中的HBV Pre-Cor

StephenW

J Med Virol. 2018 Feb 28. doi: 10.1002/jmv.25068. [Epub ahead of print]
HBV Pre-Core mutant in genotype-D infected children is selected during HBeAg/anti-HBe seroconversion and leads to HBeAg negative chronic hepatitis B in adulthood.Colombatto P1, Barbera C2, Bortolotti F3, Maina AM1, Moriconi F1, Cavallone D1, Calvo P2, Oliveri F1, Bonino F4, Brunetto MR1,5.
Author information
1Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy.2Paediatric Gastroenterology Unit, Regina Margherita Children Hospital, Torino, Italy.3University of Padova, Padova, Italy.4University of Pittsburgh Medical Center Institute for Health, Chianciano Terme, Siena, Italy, and Fondazione Italiana Fegato, AREA Science Park, Campus Basovizza, Trieste, Italy.5Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

AbstractBACKGROUND: Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of Pre-Core HBV mutant (Pre-C mt) selection with virological/clinical outcomes in children followed-up until adulthood.
METHODS: Eighty subjects (50-M/30-F), 70 HBeAg-positive (87.5%) and 10 (12.5%) HBeAg-negative/anti-HBe-positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2-17) years, were followed-up for 14.3 years (range: 1.1-24.5); 46 (57.5%) received IFN treatment. HBV-DNA and q-HBsAg were tested by commercial assays, Pre-Core 1896 mt by direct-sequence, oligo-hybridization-assay and allele-specific-PCR (sensitivity: 30%, 10% and 0.1% of total viremia).
RESULTS: HBeAg/anti-HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg-negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg-negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV-DNA and HBsAg were lower in SC than in no-SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005 and 4.72 vs 5.04 Log IU/ml, P = 0.015). The prevalence of Pre-C mt increased rapidly (10% to 40%) around SC. Eventually, Pre-C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P < 0.001). HBV-DNA levels remained slightly higher in carriers of HBeAg negative infection with dominant/mixed Pre-C mt populations, than in those with dominant Pre-C wt (mean Log IU/mL: 3.83 and 3.42 vs 2.67, P = 0.007) Conclusions. Pre-C-mt is selected during HBeAg/anti-HBe SC in children with poor control of HBV replication, leading to HBeAg-negative chronic-active-hepatitis during adulthood. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: Antiviral agents, Genetic variability; Evolution, Persistent infection; Hepatitis B virus; Infection, Immune responses, Immune system; Pathogenesis; Virus classification, Interferon

PMID:29488227DOI:10.1002/jmv.25068

StephenW

J Med Virol。 2018年2月28日。doi：10.1002 / jmv.25068。 [电子版提前打印]
在HBeAg /抗HBe血清转换期间选择基因型-D感染儿童中的HBV Pre-Core突变体，并在成年期导致HBeAg阴性慢性乙型肝炎。
Colombatto P1，Barbera C2，Bortolotti F3，Maina AM1，Moriconi F1，Cavallone D1，Calvo P2，Oliveri F1，Bonino F4，Brunetto MR1,5。
作者信息

1
    肝病病毒分子遗传学和病理学实验室，托斯卡纳地区慢性肝病和癌症参考中心，意大利比萨大学医院。
2
    意大利都灵Regina Margherita儿童医院小儿消化科。
3
    帕多瓦大学，意大利帕多瓦大学。
4
    匹兹堡大学医疗中心卫生研究所，意大利锡耶纳基安奇安诺泰尔梅，以及义大利基金会Fegato，科学园，校园Basovizza，意大利的里雅斯特。
五
    内科，比萨大学临床和实验医学系，比萨，意大利。

抽象
背景：

在儿童时期选择HBeAg缺陷型HBV突变体（mt）可能影响成人的感染结果。本研究的目的是将前核心HBV突变体（Pre-C mt）选择的动态与儿童随访期间的病毒学/临床结果相关联直至成年。
方法：

入院时有80名受试者（50-M / 30-F），70名HBeAg阳性（87.5％）和10名（12.5％）HBeAg阴性/抗-HBe阳性，大部分基因型D感染（91.2％），年龄6.5（范围：0.2-17）年，随访14。3年（范围：1.1-24.5）; 46名（57.5％）接受IFN治疗。 HBV-DNA和q-​​HBsAg通过商业化验，核心1896mt通过直接序列，寡聚杂交测定和等位基因特异性PCR（灵敏度：总病毒血症的30％，10％和0.1％）进行测试。
结果：

HBeAg /抗HBe血清转换（SC）发生在55/70（78.6％）的儿童中。 SC后8例（14.6％）发生HBeAg阴性慢性肝炎（CHB），41例（74.5％）仍存在HBeAg阴性慢性感染，6例（10.9％）HBsAg消失。基线HBV-DNA和HBsAg低于无SC患儿（中位数：7.35 vs 8.95 Log IU / mL，P = 0.005和4.72 vs 5.04 Log IU / ml，P = 0.015）。 Pre-C mt的发病率在SC附近迅速增加（10％至40％）。最终，在100％CHB，33％没有疾病的慢性感染和16％清除HBsAg的受试者中检测到Pre-C mt（P <0.001）。 HBeAg阴性感染携带主要/混合Pre-C mt群体的HBV-DNA水平仍略高于具有Pre-C wt占优势的患者（平均Log IU / mL：3.83和3.42比2.67，P = 0.007）。 。在HBeAg /抗HBe SC期间，对HBV复制控制不佳的儿童选择Pre-C-mt，导致成人期HBeAg阴性慢性活动性肝炎。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：

抗病毒药物，遗传变异性;进化，持续感染;乙型肝炎病毒;感染，免疫反应，免疫系统;发病;病毒分类，干扰素

结论：
    29488227
DOI：
    10.1002 / jmv.25068