Characterization of the basal core promoter and precore regions in anti-HBe-positive inactive carriers of hepatitis B virus

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http://www.ijidonline.com/article/PIIS1201971211000130/abstract?rss=yes

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASE

Characterization of the basal core promoter and precore regions in

anti-HBe-positive inactive carriers of hepatitis B virus

María Mora González López Ledesmaa, Galdameb, Belén Bouzasc, Luciana

Tadeya, Beatriz Livellarab, Silvina Giulianoc, Marcela Viautb, Silvia Pazc, Hugo

Fainboimc, Gadanob, Rodolfo Camposa, Diego Flichmana

Received 8 September 2010; received in revised form 15 December 2010; accepted

21 December 2010. published online 03 March 2011.

Corrected Proof

Summary

Background

The study of hepatitis B virus (HBV) genomic heterogeneity has become a major

issue in investigations aimed at understanding the relationship between HBV

mutants and the wide spectrum of clinical and pathological conditions associated

with HBV infection. Although most chronically infected HBV patients are inactive

carriers, several virological aspects of this state remain unclear.

Methods

In order to determine the prevalence and clinical significance of mutations in

the basal core promoter (BCP) and precore (pC) regions among inactive carriers,

the nucleotide sequences from 41 inactive carriers were analyzed and compared

with those from 29 individuals with chronic active hepatitis.

Results

Genotypes A (24.3%), D (37.1%), F1b (12.9%), and F4 (18.6%) were the most

prevalent. Mutations in the BCP/pC regions were observed in most of the inactive

carriers (92.7%) and in most of the patients with chronic active hepatitis

(93.1%). The prevalence of mutation 1764A was significantly higher in patients

with chronic active hepatitis (65.5%) than in inactive carriers (36.6%)

(p=0.038), whereas the prevalences of mutations at the other positions analyzed

were not significantly different. Older patients (>50 years) showed BCP/pC

patterns with a higher number of substitutions. Mutations were found to be

biased by genotype: the 1896A mutation was highly prevalent in genotypes D and

F4, while alternative substitutions in the pC region were more prevalent in

genotypes A and F1b.

Conclusions

Mutations in the BCP/pC regions are the hallmark of chronic anti-HBe-positive

individuals; nevertheless, the even distribution of mutations in active and

inactive carriers suggests that BCP/pC mutations may occur during HBV infection

not strictly related to the HBV infection activity.

Corresponding Editor: Jane Zuckerman, London, UK

a Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos

Aires, 1113 Buenos Aires, Argentina

b Unidad de Hepatología, Hospital Italiano Buenos Aires, Buenos Aires, Argentina

c Unidad de Hepatología, Hospital de Infecciosas “F. Muñiz”, Buenos Aires,

Argentina

Corresponding author. Tel.: +54 11 4 9648200x8264.

PII: S1201-9712(11)00013-0

doi:10.1016/j.ijid.2010.12.009

© 2011 Published by Elsevier Inc.

[Guest guest]

http://www.ijidonline.com/article/PIIS1201971211000130/abstract?rss=yes

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASE

Characterization of the basal core promoter and precore regions in

anti-HBe-positive inactive carriers of hepatitis B virus

María Mora González López Ledesmaa, Galdameb, Belén Bouzasc, Luciana

Tadeya, Beatriz Livellarab, Silvina Giulianoc, Marcela Viautb, Silvia Pazc, Hugo

Fainboimc, Gadanob, Rodolfo Camposa, Diego Flichmana

Received 8 September 2010; received in revised form 15 December 2010; accepted

21 December 2010. published online 03 March 2011.

Corrected Proof

Summary

Background

The study of hepatitis B virus (HBV) genomic heterogeneity has become a major

issue in investigations aimed at understanding the relationship between HBV

mutants and the wide spectrum of clinical and pathological conditions associated

with HBV infection. Although most chronically infected HBV patients are inactive

carriers, several virological aspects of this state remain unclear.

Methods

In order to determine the prevalence and clinical significance of mutations in

the basal core promoter (BCP) and precore (pC) regions among inactive carriers,

the nucleotide sequences from 41 inactive carriers were analyzed and compared

with those from 29 individuals with chronic active hepatitis.

Results

Genotypes A (24.3%), D (37.1%), F1b (12.9%), and F4 (18.6%) were the most

prevalent. Mutations in the BCP/pC regions were observed in most of the inactive

carriers (92.7%) and in most of the patients with chronic active hepatitis

(93.1%). The prevalence of mutation 1764A was significantly higher in patients

with chronic active hepatitis (65.5%) than in inactive carriers (36.6%)

(p=0.038), whereas the prevalences of mutations at the other positions analyzed

were not significantly different. Older patients (>50 years) showed BCP/pC

patterns with a higher number of substitutions. Mutations were found to be

biased by genotype: the 1896A mutation was highly prevalent in genotypes D and

F4, while alternative substitutions in the pC region were more prevalent in

genotypes A and F1b.

Conclusions

Mutations in the BCP/pC regions are the hallmark of chronic anti-HBe-positive

individuals; nevertheless, the even distribution of mutations in active and

inactive carriers suggests that BCP/pC mutations may occur during HBV infection

not strictly related to the HBV infection activity.

Corresponding Editor: Jane Zuckerman, London, UK

a Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos

Aires, 1113 Buenos Aires, Argentina

b Unidad de Hepatología, Hospital Italiano Buenos Aires, Buenos Aires, Argentina

c Unidad de Hepatología, Hospital de Infecciosas “F. Muñiz”, Buenos Aires,

Argentina

Corresponding author. Tel.: +54 11 4 9648200x8264.

PII: S1201-9712(11)00013-0

doi:10.1016/j.ijid.2010.12.009

© 2011 Published by Elsevier Inc.