Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3

Abstract Background At the end of the 1970s, in Italy more than 2% of the general population was HBsAg carrier. In the late ‘70s and late ‘80s, two remarkable events might have impacted on HBV strains transmitted in North-East Italy: (a) the increased HBV incidence due to parenteral drugs between 19...

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Main Authors: Roberto Bruni, Umbertina Villano, Stefania Taffon, Michele Equestre, Elisabetta Madonna, Paola Chionne, Angela Candido, Stefano Dettori, Giulio Pisani, Maria Rapicetta, Flavia Bortolotti, Anna Rita Ciccaglione
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Language:English
Published: BMC 2020-01-01
Series:BMC Infectious Diseases
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Online Access:https://doi.org/10.1186/s12879-019-4713-9
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author Roberto Bruni
Umbertina Villano
Stefania Taffon
Michele Equestre
Elisabetta Madonna
Paola Chionne
Angela Candido
Stefano Dettori
Giulio Pisani
Maria Rapicetta
Flavia Bortolotti
Anna Rita Ciccaglione
author_facet Roberto Bruni
Umbertina Villano
Stefania Taffon
Michele Equestre
Elisabetta Madonna
Paola Chionne
Angela Candido
Stefano Dettori
Giulio Pisani
Maria Rapicetta
Flavia Bortolotti
Anna Rita Ciccaglione
author_sort Roberto Bruni
collection DOAJ
description Abstract Background At the end of the 1970s, in Italy more than 2% of the general population was HBsAg carrier. In the late ‘70s and late ‘80s, two remarkable events might have impacted on HBV strains transmitted in North-East Italy: (a) the increased HBV incidence due to parenteral drugs between 1978 and 1982; (b) the preventive anti-HIV educational campaign, started locally in 1985. Methods To address if those events impacted on circulating HBV variants, acute cases occurred in North-East Italy in 1978–79 (n = 50) and 1994–95 (n = 30) were retrospectively analysed. HBV sequences obtained from serum samples were subjected to phylogenetic analysis and search for BCP/pre-core and S mutations. Results HBV-D was the most prevalent genotype in both 1978–79 (43/50, 86%) and 1994–95 (24/30, 80.0%), with HBV-A in all but one remaining cases. Among HBV-D cases, sub-genotype HBV-D3 was the most prevalent (25/29, 86.2% in 1978–79; 13/16, 81.2% in 1994–95), with HBV-D1 and HBV-D2 in the remaining cases. All HBV-A cases were sub-genotype A2. Single and multiple BCP/pre-core mutations, responsible for HBeAg(−) hepatitis, were detected in 6/50 (12%) cases in 1978/79 vs. 12/30 (40.0%) in 1994/95 (p = 0.006). They were found exclusively in HBV-D; in the most abundant sub-genotype, HBV-D3, they were detected in 2/25 (8%) cases in 1978–79 vs. 6/13 (46%) in 1994–95 (p = 0.011). No vaccine escape S mutations were observed. The IDU risk factor was significantly more frequent in 1994–95 (8/30, 26.7%) than in 1978–79 (4/50, 8%) (p = 0.048). Conclusions The above mentioned epidemiological and public health events did not affect the proportion of genotypes and sub-genotypes that remained unchanged over 16 years. In contrast, the proportion of BCP/pre-core mutants increased more than three-fold, mostly in HBV-D3, a sub-genotype highly circulating in IDUs; drug abuse likely contributed to the spread of these mutants. The findings contribute to explain a previously described major change in HBV epidemiology in Italy: the proportion of HBeAg(−) cases in the carrier cohort changed from low in late 1970s, to high at the beginning of the 2000s. In addition to other recognized factors, the increased circulation of BCP/pre-core mutants likely represents a further factor that contributed to this change.
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spelling doaj.art-ba84a680ee6748e0b651441d066ec6d72022-12-21T20:01:22ZengBMCBMC Infectious Diseases1471-23342020-01-012011910.1186/s12879-019-4713-9Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3Roberto Bruni0Umbertina Villano1Stefania Taffon2Michele Equestre3Elisabetta Madonna4Paola Chionne5Angela Candido6Stefano Dettori7Giulio Pisani8Maria Rapicetta9Flavia Bortolotti10Anna Rita Ciccaglione11Department of Infectious Diseases, Istituto Superiore di SanitàDepartment of Infectious Diseases, Istituto Superiore di SanitàDepartment of Infectious Diseases, Istituto Superiore di SanitàDepartment of Neurosciences, Istituto Superiore di SanitàDepartment of Infectious Diseases, Istituto Superiore di SanitàDepartment of Infectious Diseases, Istituto Superiore di SanitàNotified Body 0373, Istituto Superiore di SanitàNotified Body 0373, Istituto Superiore di SanitàNational Centre for the Control and Evaluation of Medicines, Istituto Superiore di SanitàDepartment of Infectious Diseases, Istituto Superiore di SanitàDepartment of Experimental and Clinical Medicine, University of PaduaDepartment of Infectious Diseases, Istituto Superiore di SanitàAbstract Background At the end of the 1970s, in Italy more than 2% of the general population was HBsAg carrier. In the late ‘70s and late ‘80s, two remarkable events might have impacted on HBV strains transmitted in North-East Italy: (a) the increased HBV incidence due to parenteral drugs between 1978 and 1982; (b) the preventive anti-HIV educational campaign, started locally in 1985. Methods To address if those events impacted on circulating HBV variants, acute cases occurred in North-East Italy in 1978–79 (n = 50) and 1994–95 (n = 30) were retrospectively analysed. HBV sequences obtained from serum samples were subjected to phylogenetic analysis and search for BCP/pre-core and S mutations. Results HBV-D was the most prevalent genotype in both 1978–79 (43/50, 86%) and 1994–95 (24/30, 80.0%), with HBV-A in all but one remaining cases. Among HBV-D cases, sub-genotype HBV-D3 was the most prevalent (25/29, 86.2% in 1978–79; 13/16, 81.2% in 1994–95), with HBV-D1 and HBV-D2 in the remaining cases. All HBV-A cases were sub-genotype A2. Single and multiple BCP/pre-core mutations, responsible for HBeAg(−) hepatitis, were detected in 6/50 (12%) cases in 1978/79 vs. 12/30 (40.0%) in 1994/95 (p = 0.006). They were found exclusively in HBV-D; in the most abundant sub-genotype, HBV-D3, they were detected in 2/25 (8%) cases in 1978–79 vs. 6/13 (46%) in 1994–95 (p = 0.011). No vaccine escape S mutations were observed. The IDU risk factor was significantly more frequent in 1994–95 (8/30, 26.7%) than in 1978–79 (4/50, 8%) (p = 0.048). Conclusions The above mentioned epidemiological and public health events did not affect the proportion of genotypes and sub-genotypes that remained unchanged over 16 years. In contrast, the proportion of BCP/pre-core mutants increased more than three-fold, mostly in HBV-D3, a sub-genotype highly circulating in IDUs; drug abuse likely contributed to the spread of these mutants. The findings contribute to explain a previously described major change in HBV epidemiology in Italy: the proportion of HBeAg(−) cases in the carrier cohort changed from low in late 1970s, to high at the beginning of the 2000s. In addition to other recognized factors, the increased circulation of BCP/pre-core mutants likely represents a further factor that contributed to this change.https://doi.org/10.1186/s12879-019-4713-9Hepatitis B virusHBVGenotypeSub-genotypeBasal core promoterPre-core
spellingShingle Roberto Bruni
Umbertina Villano
Stefania Taffon
Michele Equestre
Elisabetta Madonna
Paola Chionne
Angela Candido
Stefano Dettori
Giulio Pisani
Maria Rapicetta
Flavia Bortolotti
Anna Rita Ciccaglione
Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
BMC Infectious Diseases
Hepatitis B virus
HBV
Genotype
Sub-genotype
Basal core promoter
Pre-core
title Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
title_full Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
title_fullStr Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
title_full_unstemmed Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
title_short Retrospective analysis of acute HBV infections occurred in 1978–79 and 1994–95 in North-East Italy: increasing prevalence of BCP/pre-core mutants in sub-genotype D3
title_sort retrospective analysis of acute hbv infections occurred in 1978 79 and 1994 95 in north east italy increasing prevalence of bcp pre core mutants in sub genotype d3
topic Hepatitis B virus
HBV
Genotype
Sub-genotype
Basal core promoter
Pre-core
url https://doi.org/10.1186/s12879-019-4713-9
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