循环中的Pre-S / S准种是否会影响HBV感染的HBeAg阴性阶段中的乙

StephenW

Aliment Pharmacol Ther. 2020 May 11. doi: 10.1111/apt.15753. [Epub ahead of print]
Do the circulating Pre-S/S quasispecies influence the hepatitis B virus surface antigen levels in the HBeAg negative phase of HBV infection?
Cavallone D1,2, Ricco G1,2, Oliveri F2, Colombatto P2, Moriconi F2, Coco B2, Romagnoli V2, Salvati A2, Surace L2, Bonino F3, Brunetto MR1,2,3.
Author information

1
    Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
2
    Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Pisa University Hospital, Pisa, Italy.
3
    Biostructure and Bio-imaging Institute of National Research Council of Italy, Naples, Italy.

Abstract
BACKGROUND:

Virus, host factors and their interplay influence Hepatitis B surface Antigen serum levels during Hepatitis B Virus (HBV) infection course and treatment.
AIM:

To study the Pre-S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype-D, HBsAg carriers.
METHODS:

We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV-DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV-DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV-DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre-S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M-muts) on HBsAg.
RESULTS:

HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 [-1.10/4.06] vs 3.62 [2.41/4.92] log10 IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log10 IU/mL, P < 0.001). M-muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre-S2 (17.6%) than Pre-S1 (5.8%) and Small-S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M-muts (3.56 [0.95/4.38] vs 3.17 [-1.10/4.92] log10 IU/mL, P < 0.001), but comparable in carriers with or without M-mut when considering separately ENI + GZ (2.84 [0.95/3.89] vs 2.61 [-1.10/4.06] log10 IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log10 IU/mL, P = 0.37). Infection phase (β: 0.422, P < 0.001), age (β: -0.260, P < 0.001), ALT (β: -0.103, P = 0.045), liver stiffness (β: -0.118, P = 0.039) and HBV-DNA (β: 0.384, P < 0.001), but not M-mut were independently associated with HBsAg serum levels.
CONCLUSIONS:

In HBeAg negative, genotype-D, carriers Pre-S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV.

© 2020 John Wiley & Sons Ltd.

PMID:
    32390175
DOI:
    10.1111/apt.15753

StephenW

食品药理学。 2020年5月11日。doi：10.1111 / apt.15753。 [Epub提前发布]
循环中的Pre-S / S准种是否会影响HBV感染的HBeAg阴性阶段中的乙型肝炎病毒表面抗原水平？
Cavallone D1,2，Ricco G1,2，Oliveri F2，Colombatto P2，Moriconi F2，Coco B2，Romagnoli V2，Salvati A2，Surace L2，Bonino F3，Brunetto MR1,2,3。
作者信息

1个
意大利比萨大学临床和实验医学系。
2
比萨比萨大学医院，肝病科，肝炎病毒分子遗传学和病理学实验室。
3
意大利那不勒斯国家研究委员会生物结构与生物成像研究所。

抽象
背景：

病毒，宿主因素及其相互作用影响乙肝病毒（HBV）感染过程和治疗过程中的乙肝表面抗原血清水平。
目标：

在未经治疗的，HBeAg阴性，基因型D，HBsAg携带者的队列中研究Pre-S / S循环准种。
方法：

我们研究了260例携带者：71例患有HBeAg阴性感染（ENI； HBV-DNA≤2000IU / mL）； 42灰色区（GZ; HBV-DNA≤20000IU / mL）; 82例慢性肝炎（CH）和65例肝硬化（CI）（HBV-DNA> 20 000 IU / mL）。应用人群测序来鉴定负责HBsAg的任何氨基酸替代或潜在生物学/抗原影响（M-muts）的Pre-S / S基因突变。
结果：

ENI + GZ的HBsAg血清水平低于CH + CI（2.61 [-1.10 / 4.06] vs 3.62 [2.41 / 4.92] log10 IU / mL，P <0.001），而CI则低于CH（3.48 [2.41 / 4.38] vs 3.66 [2.57 / 4.92] log10 IU / mL，P <0.001）。在73（28.1％）例患者中发现了M-muts：5（7.0％）ENI，3（7.1％）GZ，26（31.7％）CH，39（60.0％）CI（P <0.001），且大多数发生在S2（17.6％）高于Pre-S1（5.8％）和Small-S（10.8％; P <0.001）。携带M-mut的携带者的总体HBsAg血清水平较高（3.56 [0.95 / 4.38] vs 3.17 [-1.10 / 4.92] log10 IU / mL，P <0.001），但与单独考虑或不携带M-mut的携带者相当ENI + GZ（2.84 [0.95 /3.89] vs 2.61 [-1.10 / 4.06] log10 IU / mL，P = 0.330]和CH + CI（3.57 [2.67 / 4.38] vs 3.63 [2.41 / 4.92] log10 IU / mL， P = 0.37）。感染期（β：0.422，P <0.001），年龄（β：-0.260，P <0.001），ALT（β：-0.103，P = 0.045），肝硬化（β：-0.118，P = 0.039）和HBV-DNA（β：0.384，P <0.001），但M-mut与HBsAg血清水平无关。
结论：

在HBeAg阴性，D型携带者中，携带者Pre-S / S异质性随肝脏疾病的严重程度而增加，但不影响HBsAg血清水平，在低病毒携带者中与有效控制HBV有关。

分级为4 +©2020 John Wiley＆Sons Ltd.

PMID：
32390175
DOI：
10.1111 / apt.15753