Do the circulating Pre-S/S quasispecies influence the hepatitis B virus surface antigen levels in the HBeAg negative phase of HBV infection?

被引：10

作者：

Cavallone, Daniela ^{[1
,2
,3
]}

Ricco, Gabriele ^{[1
,2
,3
]}

Oliveri, Filippo ^{[2
,3
]}

Colombatto, Piero ^{[2
,3
]}

Moriconi, Francesco ^{[2
,3
]}

Coco, Barbara ^{[2
,3
]}

Romagnoli, Veronica ^{[2
,3
]}

Salvati, Antonio ^{[2
,3
]}

Surace, Lidia ^{[2
,3
]}

Bonino, Ferruccio ^{[4
]}

Brunetto, Maurizia Rossana ^{[1
,2
,3
,4
]}

机构：

[1] Univ Pisa, Dept Clin & Expt Med, Pisa, Italy

[2] Pisa Univ Hosp, Hepatol Unit, Pisa, Italy

[3] Pisa Univ Hosp, Lab Mol Genet & Pathol Hepatitis Viruses, Pisa, Italy

[4] Natl Res Council Italy, Biostruct & Bioimaging Inst, Naples, Italy

来源：

ALIMENTARY PHARMACOLOGY & THERAPEUTICS | 2020年 / 51卷 / 12期

关键词：

S DELETION; SERUM-LEVELS; PEGINTERFERON ALPHA-2A; ENVELOPE PROTEINS; DISEASE; LIVER; HBSAG; DNA; ASSOCIATION; PREVALENCE;

D O I：

10.1111/apt.15753

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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] log(10)IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log(10) 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] log(10) 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] log(10)IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log(10)IU/mL, P = 0.37). Infection phase (beta: 0.422, P < 0.001), age (beta: -0.260, P < 0.001), ALT (beta: -0.103, P = 0.045), liver stiffness (beta: -0.118, P = 0.039) and HBV-DNA (beta: 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.

引用

页码：1406 / 1416

页数：11

共 40 条

[1] Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: On-treatment kinetics of HBsAg serum levels vary by HBV genotype [J].

Brunetto, Maurizia R. ;

Marcellin, Patrick ;

Cherubini, Beatrice ;

Yurdaydin, Cihan ;

Farci, Patrizia ;

Hadziyannis, Stephanos J. ;

Rothe, Vivien ;

Regep, Loredana ;

Bonino, Ferruccio .

JOURNAL OF HEPATOLOGY, 2013, 59 (06) :1153-1159

[2] Hepatitis B Surface Antigen Serum Levels Help to Distinguish Active From Inactive Hepatitis B Virus Genotype D Carriers [J].

Brunetto, Maurizia Rossana ;

Oliveri, Filippo ;

Colombatto, Piero ;

Moriconi, Francesco ;

Ciccorossi, Pietro ;

Coco, Barbara ;

Romagnoli, Veronica ;

Cherubini, Beatrice ;

Moscato, Giovanna ;

Maina, Anna Maria ;

Cavallone, Daniela ;

Bonino, Ferruccio .

GASTROENTEROLOGY, 2010, 139 (02) :483-490

[3] Hepatitis B Virus Surface Antigen Levels: A Guide to Sustained Response to peginterferon alfa-2a in HBeAg-Negative Chronic Hepatitis B [J].

Brunetto, Maurizia Rossana ;

Moriconi, Francesco ;

Bonino, Ferruccio ;

Lau, George K. K. ;

Farci, Patrizia ;

Yurdaydin, Cihan ;

Piratvisuth, Teerha ;

Luo, Kanxian ;

Wang, Yuming ;

Hadziyannis, Stephanos ;

Wolf, Eva ;

McCloud, Philip ;

Batrla, Richard ;

Marcellin, Patrick .

HEPATOLOGY, 2009, 49 (04) :1141-1150

[4] WILD-TYPE AND E-ANTIGEN-MINUS HEPATITIS-B VIRUSES AND COURSE OF CHRONIC HEPATITIS [J].

BRUNETTO, MR ;

GIARIN, MM ;

OLIVERI, F ;

CHIABERGE, E ;

BALDI, M ;

ALFARANO, A ;

SERRA, A ;

SARACCO, G ;

VERME, G ;

WILL, H ;

BONINO, F .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (10) :4186-4190

[5] Functions of the large hepatitis B virus surface protein in viral particle morphogenesis [J].

Bruss, V ;

Gerhardt, E ;

Vieluf, K ;

Wunderlich, G .

INTERVIROLOGY, 1996, 39 (1-2) :23-31

[6] High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases [J].

Chen, BF ;

Liu, CJ ;

Jow, GM ;

Chen, PJ ;

Kao, JH ;

Chen, DS .

GASTROENTEROLOGY, 2006, 130 (04) :1153-1168

[7] Different pre-S deletion patterns and their association with hepatitis B virus genotypes [J].

Chen, Bing-Fang .

WORLD JOURNAL OF GASTROENTEROLOGY, 2016, 22 (35) :8041-8049

[8] Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-Negative patients [J].

Chen, Chien-Hung ;

Hung, Chao-Hung ;

Lee, Chuan-Mo ;

Hu, Tsung-Hui ;

Wang, Jing-Houng ;

Wang, Jyh-Chwan ;

Lu, Sheng-Nan ;

Changchien, Chi-Sin .

GASTROENTEROLOGY, 2007, 133 (05) :1466-1474

[9] 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 [J].

Colombatto, Piero ;

Barbera, Cristiana ;

Bortolotti, Flavia ;

Maina, Anna M. ;

Moriconi, Francesco ;

Cavallone, Daniela ;

Calvo, Pierluigi ;

Oliveri, Filippo ;

Bonino, Ferruccio ;

Brunetto, Maurizia R. .

JOURNAL OF MEDICAL VIROLOGY, 2018, 90 (07) :1232-1239

[10] The role of quantitative hepatitis B surface antigen revisited [J].

Cornberg, Markus ;

Wong, Vincent Wai-Sun ;

Locarnini, Stephen ;

Brunetto, Maurizia ;

Janssen, Harry L. A. ;

Chan, Henry Lik-Yuen .

JOURNAL OF HEPATOLOGY, 2017, 66 (02) :398-411

← 1 2 3 4 →