Prevalence of hepatitis B infection and factors associated in children of Ivorian HBsAg carrier subjects

doi:10.4236/ojgas.2013.34040

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Open Journal of Gastroenterology, 2013, 3, 237-240 OJGas

doi:10.4236/ojgas.2013.34040 Published Online August 2013 (http://www.scirp.org/journal/ojgas/)

Prevalence of hepatitis B infection and factors associated in

children of Ivorian HBsAg carrier subjects

Koffi Alain Attia1*, Ya Henriette Kissi1, Stanislas Doffou1, Demba Bangoura1, Roseline Flora Wilson1,

Georges Bougha1, Fulgence Yao Bathaix1, Kouame Alassan Mahassadi1, Mohamed Sayegh2,

Therese N’dri-Yoman1

1Department of General Medicine and Hepato-Gastroenterology, Teaching Hospital of Yopougon, Abidjan, Côte d’Ivoire

2Medical Private hospital of Danga, Cocody, Abidjan, Côte d’Ivoire

Email: *[email protected]

Received 13 May 2013; revised 16 June 2013; accepted 1 July 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Aims of the Study: 1) Determine the Prevalence of

Hepatitis B virus (HBV) infection in children (contact

subjects) of chronic Hepatitis B surface antigen

(HBsAg) carrier subjects (index subjects); 2) Search

for factors associated with HBV infection in these

children. Patients and Methods: Retrospective-cross-

sectional study (January 5th, 2006 through December

31st, 2012). Studied parameters: biological and clini-

cal characteristics of index subjects; Prevalence of

HBsAg and Hepatitis B core antibody (HBcAb) in

their children. Search for the HBV infection associa-

ted factors in the children (univariate analyses through

Chi-square or Fisher’s exact test; multivariate analy-

sis through a backward logistic regression). Results:

Our 44 subjects’ median age was 43.1 ± 7.49 years

and 88.6% of them lived with a spouse. Average

number of children per index subjects was 2.3 ± 1.1.

Our 92 children’s median age was 9.3 ± 4.55 (ranging

from 1 to 15 years), and 43 (44.8%) were vaccinated

against HBV. HBV infection prevalence was 24%

(23/96 of which, 4 were HBsAg positive and 19 HBcAb

positive subjects without HBsAg). Independent fac-

tors associated with HBV infection in children of in-

dex subjects were HBV DNA for index subjects >2000

IU/ml (OR = 11.5; p = 0.001), existence of HBV in two

parents (OR = 7.9; p = 0.03) and absence of HBV

vaccination in the children (OR = 30.9; p = 0.003).

Conclusion: Immunization coverage for children of

index subjects was insufficient, especially before the

introduction of HBV vaccine into the enlarged vacci-

nation program. Outside vertical transmission, those

children were more exposed to HBV intrafamilial

transmission risk when they were not immunized

against HBV, when both parents were infected and

when HBV viremia in index subjects was higher than

2000 IU/ml.

Keywords: Hepatitis B Infection; Intrafamilial

Transmission; Screening

1. INTRODUCTION

Hepatitis B virus (HBV) infection is a real public health

problem worldwide and more particularly in high preva-

lence areas, such as sub-Saharan Africa [1-7], because of

its progressive complications (cirrhosis and hepatocellu-

lar carcinoma), comorbidity frequency (especially HIV

infection) and management difficulties in the particular

context of our countries with limited financial resources.

In sub-Saharan Africa, both main transmission ways are

vertical or perinatal and intrafamilial horizontal in early

childhood [5,7]. Introduction of HBV universal immuni-

zation for newborns into enlarged vaccination programs

(EVP) of our countries in Sub-Sahara dates generally from

at least two decades. In most EVP of our countries, HBV

immunization only starts from the 6th week after birth

(pentavalent or hexavalent vaccine). Moreover, owing to

anti-HBs immunoglobulins (Ig) availability problems in

our countries, passive immunoprophylaxis is almost never

associated with active immunization. Vertical and in-

trafamilial horizontal transmission risks of HBV infec-

tion remain a concern before HBV immunization, espe-

cially during children’s first six weeks of life. This study

aims to determine HBV infection prevalence among chil-

dren (contact subjects) of hepatitis B surface antigen

(HBsAg) chronic carrier subjects (index subjects) through

familial screening of HBV infection and search for fac-

tors associated with HBV infection in these children.

*Corresponding author.

Published Online August 2013 in SciRes. http://www.scirp.org/journal/ojgas

K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240

238

2. PATIENTS AND METHODS

It’s about a retrospective cross-sectional study (January

5th, 2006 through December 31st, 2012). Records of

HBsAg chronic carrier patients, with ambulatory follow-

up in two medical centers in Abidjan (University Hospi-

tal of Yopougon and Clinique Médicale Danga), were

analyzed. All the HBsAg-positive patients (index sub-

jects), whose family surrounding (contacts subjects: spouses

and children) was subjected to systematic screening for

HBV infection, were included in our study (search for

HBsAg and hepatitis B core antibody (HBcAb) in con-

tact subjects: Mini Vidas; Biomerieux, Marcy l’Etoile,

France). Subjects whose children were more than 15

years old were excluded from the study.

A systematic and minimal biological checkup was re-

alized for every index subject; the checkup included

transaminases determination (Cobas Integra 400 plus;

Roche diagnostics, Mannheim, Germany), a search for

HBeAg, anti-HBeAb and anti-HBcAb, anti-HCV Anti-

bodies (Mini Vidas; Biomerieux, Marcy l’Etoile, Fran-

ce), DNA HBV determination using a real-time PCR as-

say (Cobas Amplicor HBV Monitor assay, threshold of

detectability 35 copies/ml or 6 IU/ml; Roche Diagnostics)

and HIV test (screening test using Determine and con-

firmation test using Genie II).

Main evaluation criteria was the existence of HBV in-

fection in index subjects’ children testified by presence

of HBcAb. The infection was past when HBsAg was

negative and present when HBsAg was positive.

We searched for HBV associated factors in children

through univariate analyses (Chi-square or Fisher’s exact

test) and a multivariate analysis (backward logistic re-

gression). All variables of which “p” was under 0.30 in

univariate analysis were included in initial model of mul-

tivariate analysis. Alpha threshold was 5% for bilateral

formulation.

3. RESULTS

HVB infection screening among the family circle of the

44 studied index subjects was about 39 spouses and 96

children. Index subjects’ median age was 43.1  7.49

years ranging from 28 to 58. Average number of children

per subject index was 2.3  1.1 ranging from 1 to 5 chil-

dren. HIV test was negative in all their parents. Charac-

teristics of index subjects and their children at inclusion

are summed up in Tables 1 and 2.

The 96 children’s median age was 9.3 ± 4.55 years

ranging from 1 to 15 years. HBV infection in children

was 24% (HBcAb were presents in 23 out of 96). HBsAg

was present in only 4 of these 23 children (17.4%), that

is an overall prevalence of 4.2% (4 children out of 96).

Three of these 4 HBsAg-positive children had not re-

ceived any Hepatitis B vaccine (one aged 14 years old

Table 1. Baseline characteristics of 44 index subjects.

Baseline characteristics of 44 in d ex su b jects

Median age, years (IQR*) 42 38 - 47

Female gender, n (%) 20/44 (45.5)

Positive HBe antigen (Ag), n (%) 11/44 (25)

Positive anti-HBe antibodies (Ab), n (%) 33/44 (75)

HBV DNA ≥ 2000 IU/ml, n (%) 18/44 (40.9)

Serum transaminase level (ALT*) > UNV*, n (%) 14/44 (31.8)

Spouse at home, n (%) 39/44 (88.6)

HBV complete vaccination of spouses, n (%) 05/39 (12.8)

HBV serological status of spouses:

Positive HBsAg and positive HBcAb, n (%) 06/39 (15.4)

Positive HBcAb without HBsAg, n (%) 17/39 (43.6)

Negative HBsAg and negative HBcAb, n (%) 16/39 (41)

Median number of children (IQR) 2 (1 - 3)

*IQR = Interquartile range; HBV DNA = Hepatitis B virus DNA; ALT =

Alanine aminotransferase (UNV: 50 UI/mL); UNV = Upper normal value.

Table 2. Baseline characteristics of 96 children.

Baseline characteristics of 96 children

Median age, years (IQR*) 9 (5 - 14)

Female gender, n (%) 52/96 (54.2)

HBV vaccination coverage of children, n (%) 43/96 (44.8)

HBV serological status of children:

Positive HBsAg and positive HBcAb, n (%) 04/96 (4.2)

Positive HBcAb without HBsAg, n (%) 19/96 (19.8)

Negative HBsAg and negative HBcAb, n (%) 73/96 (76)

*IQR = Interquartile range.

and two aged 15 years old). The 4th one aged 2 years old

was immunized within the framework of the enlarged

vaccination program (3 doses at the 6th, 10th and 14th

week after birth). Vaccination coverage was 44.8% (43

children out of 96). These vaccination coverage among

children above 12 years was significantly less than that

of those aged 12 or less (1 of 37 children >12 years, that

is 2.7% versus 42 of 59 children 12 years, that is 71.2%;

p < 0.001). None of the 96 children had drug addiction

history or risk sexual behavior. Relationship between

HBV serological status of children and baseline charac-

teristics of index subjects and their children is summed

up in Table 3.

4. DISCUSSION

In HBV high-endemic areas, like Côte d’Ivoire, the two

main transmission ways are perinatally or vertical trans-

mission and intrafamilial hor zontal transmission in early i

K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240

239

OJGas

Table 3. Relationship between HBV serological status of children and baseline characteristics of index subjects and their children.

Univariate analyses

Multivariate analysis

HBV serological status of children

Infected Uninfected p HR (95% CI) p Baseline characteristics

n (%) n (%)

Children >12 years 16/23 (69.6) 21/73 (28.8) <0.001

Male gender children 10/23 (43.5) 34/73 (46.6) 0.795

Unvaccined children 22/23 (95.7) 31/73 (42.5) <0.001 30.9 (3.8 - 95.2) 0.003

Index subjects >42 years* 17/23 (73.9) 30/73 (41.1) 0.006

Female gender index subjects 5/23 (21.7) 36/73 (49.3) 0.02

Both parents’ infected* 22/23 (95.7) 34/65 (52.3) <0.001 7.9 (1.9 - 60.2) 0.03

Vaccined spouses* 1/23 (4.4) 8/65 (12.3) 0.436

Biological results of index subjects

ALT* > UNV* 14/23 (60.9) 21/73 (28.8) 0.005

Positive HBeAg 14/23 (60.9) 9/73 (12.3) <0.001

HBV DNA* ≥2000 IU/ml 17/23 (73.9) 21/73 (28.8) <0.001 11.5 (2.7 - 25.2) 0.001

*Median age of index subjects, results for 88 children of 39 index subjects living with a regular spouse; ALT = Alanine aminotransferase (UNV: 50 UI/mL);

UNV = Upper normal value; HBV DNA = Hepatitis B virus DNA.

childhood [5,7]. From teenage, there exist other HBV

transmission additional risks, especially sexual transmis-

sion during unprotected intercourse and drug addiction

[5,7]. We excluded from our study all parents whose

children were above 15 years old to limit weight of all

these additional factors.

Most of index subjects were married and had at least

two children. HBV infection prevalence in children of

index subjects in our study was 24%. That just shows the

importance of HBV infection systematic screening of the

HBsAg-positive subjects’ family circle.

Out of 96 children of index subjects, only 43 were

immunized (44.8%). This weak immunization coverage

was above all observed before HBV vaccine integration

of into the EVP in 2000. Indeed, rate of immunized chil-

dren aged above 12 years was 2.7% and that of the chil-

dren aged 12 years or less was 71.2% (p < 0.001).

Among the 43 immunized children, only one aged 2

years had been screened HBsAg positive. The latter must

have been infected during perinatal period, before ad-

ministration of the 1st HBV vaccine dose of the 6th week.

HBV vaccine must therefore be privileged in delivery

room to be more efficient (immunization at birth and par-

ticularly during the 12 first hours). Indeed, in two obser-

vational cross-sectional studies made in sub-Saharan

Africa, HBV infection vertical transmission rate in new-

borns of HBsAg mothers was 32.8% [8] and 37.1% [9].

Transmission rate was significantively associated with

HBeAg mother status. When HBeAg was present in the

mother, infected newborns rate was respectively 66.7%

[8] and 54.5% [9] whereas it was respectively 26.9% [8]

et 29.2% [9] when HBeAg was absent in mother. In ad-

dition, in children who escaped form vertical transmis-

sion, there exist a risk of horizontal intrafamilial trans-

mission before immunoprophylaxis through vaccination;

that risk of horizontal intrafamilial transmission is fa-

vored by promiscuity and share of objects between par-

ents and children or between children themselves [10].

Three independent factors were significantively asso-

ciated with HBV in children of index subjects: a HBV

viremia higher than 2000 IU/ml in index subjects, exis-

tence of HBV infection in two parents and absence of

HBV vaccine for children. Many works have showed

that the key risk factor for HBV infection vertical trans-

mission was viremia in mother within perinatal period

[11-15]. Viremia in parents is as well an important risk

factor for horizontal intrafamilial transmission of HBV

infection [16], especially in children who escaped from

vertical transmission and who did not receive HBV vac-

cine. Owing to promiscuity, intrafamilial transmission

risk for the infection is all the more important since both

parents are infected. Even though it is not always easy in

studies to put things in perspective between vertical

transmission and horizontal intrafamilial transmission,

there seems the existence of a significative association

between female index subjects and HBV high prevalence

in these parents’ children [17-19]. Of these three risk

factors identified in our study, the most easily controlla-

K. A. Attia et al. / Open Journal of Gastroenterology 3 (2013) 237-240

240

ble is HBV vaccine. Current vaccinal strategy must be

modified on the one hand starting immunization from

birth in all children whatever HBV status the mother has,

on the other hand, prescribing a nucleosidic analogs from

the 28th week to HBsAg-positive mothers who have

strong HBV viremia. So, even if children are systemati-

cally immunized at birth, searching for HBsAg in preg-

nant women must be made compulsory and quantify

HBV load in HBsAg-positive pregnant women in order

to identify those to whom a treatment through nucleosi-

dic analogs will be proposed for maximal reduction of

HBV infection perinatal transmission. Acquired immu-

nization through vaccination will allow to later prevent-

ing children from other HBV transmission risks, espe-

cially horizontal intrafamilial transmission.

5. CONCLUSION

Immunization coverage for children of our index subjects

was insufficient, especially before introduction of HBV

vaccine into the EVP. Outside vertical transmission,

those children were more exposed to HBV intrafamilial

transmission when they were not immunized against

HBV, when both parents were infected and when HBV

viremia of index subjects was higher than 2000 IU/ml.

Immunization coverage must therefore be improved, im-

munization must be started at birth and nucleosidic ana-

logs must be proposed to HBsAg-positive pregnant wo-

men with strong viremia.

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