Научная статья на тему 'HEPATITIS B VERTICAL TRANSFER AND ITS RISK FACTORS IN PREGNANT WOMEN IN THE EASTERN PART OF IRAN'

HEPATITIS B VERTICAL TRANSFER AND ITS RISK FACTORS IN PREGNANT WOMEN IN THE EASTERN PART OF IRAN Текст научной статьи по специальности «Фундаментальная медицина»

CC BY
12
2
i Надоели баннеры? Вы всегда можете отключить рекламу.
i Надоели баннеры? Вы всегда можете отключить рекламу.

Похожие темы научных работ по фундаментальной медицине , автор научной работы — Moghadam M.N., Amirian S., Afshari M., Parooie F., Keikhaie K.R.

iНе можете найти то, что вам нужно? Попробуйте сервис подбора литературы.
i Надоели баннеры? Вы всегда можете отключить рекламу.

Текст научной работы на тему «HEPATITIS B VERTICAL TRANSFER AND ITS RISK FACTORS IN PREGNANT WOMEN IN THE EASTERN PART OF IRAN»

11. Magalhäes da Silva T, Rocha AV, Lacchini R, Marques CR, Silva ES, Tanus-Santos JE, Rios-Santos F. Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population. Gene. 2012 Jul 10;502(2):142-6.

doi: https://doi.org/10.1016/j.gene.2012.04.047

12. Mudassar IB, Yew KK, Thambiraja R, Sulong S, Ghulam RA, Ahmad TL. Microvascular endothelial function and primary open angle glaucoma. Ther Adv Ophthalmol. 2019;11:2515841419868100.

doi: https://doi.org/10.1177/2515841419868100

13. Picciano AL, Crane BR. A nitric oxide synthase-like protein from Synechococcus produces NO/NO3-

from l-arginine and NADPH in a tetrahydrobiopterin-and Ca2+-dependent manner. J Biol Chem. 2019;294(27): 10708-19. doi: https://doi.org/10.1074/jbc.RA119.008399

14. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-7.

doi: https://doi.org/10.1136/bjo.2005.081224

15. Salari N, Bokaee S, Farshchian N, Mohammadi M, Kazeminia M. The role of polymorphisms rs2070744 and rs1799983 eNOS gene in patients with POAG: a systematic review and meta-analysis. Int Ophthalmol. 2021 Apr 10. Epub ahead of print. PMID: 33837898. doi: https://doi.org/10.1007/s10792-021-01832-y

Crana Hagmm^a go pegaKmi' 03.08.2021

UDC 616.36-002.2-02-07:618.3-06-036.3-053.2(55) https://doi.Org/10.26641/2307-0404.2022.1.254377

M.N. Moghadam, hepatitis b vertical transfer

& Amirian, and its risk factors

M. Afshari, in pregnant women

F Parooie

K.R. Keikhaie, ^ In the eastern part of iran

I. Shahramian ,

A. Bazi,

P. Ostadrahimi,

M. Sheikh,

H. Mirzaie,

A. Aminisefat

Zabol University of Medical Sciences

Pediatric Gastroenterology and Hepatology Research Center Zabol, Iran

Забольский унгверситет медичних наук

Дослгдницький центр дитячо'1 гастроентерологИ та гепатологИ Забол, 1ран

е-mail: irajshahramian@gmail.com

Цитування: Медичш перспективы. 2022. Т. 27, № 1. С. 123-131 Cited: Medicniperspektivi. 2022;27(1):123-131

Key words: Hepatitis B infection, HBV, Vertical transmission Ключовi слова: ¡нфекцгя гепатиту B, HBV, вертикальна передача Ключевые слова: инфекция гепатита В, HBV, вертикальная передача

22/ Том XXVII/1

123

Abstract. Hepatitis B vertical transfer and its risk factors in pregnant women in the eastern part of Iran. Moghadam M.N., Amirian S., Afshari M., Parooie F., Keikhaie K.R., Shahramian I., Bazi A., Ostadrahimi P., Sheikh M., Mirzaie H., Aminisefat A. One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT). Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process, completely. We conducted this study aiming at investigating VT mechanism and risk factors in this region. The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-Al-Momenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study all samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA). All statistical analyzes were performed using SPSS version 22 software. Totally 43 infants of HBS antigen positive mothers were investigated. HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. There was no significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065). Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered from positive viral load mothers, the observed difference was also remained non-significant (p=0.978). Our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility ofplacenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their children.

Реферат. Вертикальна передача гепатиту В та його фактори ризику у вагггиих жшок у схщнш частиш 1рану. Могадам М.Н., Амiрiан С., Афшарi М., Паруi Ф., Кейхаi Х.Р., Шахрампаи I., Базi А., Остадрахiмi П., Шейх М., МiрзаT Х., Амшкефат А. Одтею з основних причин хротчного гепатиту е передача його eid Mamepi до дитини, яка також вiдомa як вертикальна передача (ВП). Хоча е кшька до^джень, що стосуються механ1зму ВП та ii фaкmоpiв ризику, жодному з цих до^джень не вдалося повнктю пояснити цей процес. Це до^дження проведено з метою вивчення механизму ВП та фaкmоpiв ризику у вaгimних жток у схiднiй чaсmинi 1рану. Це до^дження було описово-аналтичним мiжсeкmоpaльним до^дженням вaгimних жток з позитивним результатом HBS Ag, яке проводилося з березня 2018 року до березеня 2020 року в лiкapнi Ам-р-Аль-Момент у Зaболi, пpовiнцiя Останч-Белуджистан, 1ран. У цьому до^джент вс зразки були пepeвipeнi на нaявнiсmь мapкepiв вipусу гепатиту В (HBV) (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, i HBV-DNA) та anti-HCV за допомогою iмунофepмeнmного анализу (1ФА). Ус статистичш аналгзи проводили за допомогою программного забезпечення SPSS версп 22. Усього було до^джено 43 немовляти мamepiв з позитивним антигеном HBS. Антитшо до HBe та антиген HBe виявлено у 25 (62,5%) та 2 (5%) мamepiв вiдповiдно. Не було досmовipноi piзницi мiж новонародженими з тфекщею гепатиту В та без нього вiдносно вк мamepi (p=0,216), mpивaлосmi тфекцп в мamepi (p=0,892), AST (0,779), AL (0,449) та ALP (0,065). Mamepi з позитивним вipусним навантаженням пiд час вaгimносmi народжували новонароджених з позитивним антигеном HBS набагато частше, нiж мamepi з негативним антигеном HBS. Однак ця pi-зниця не була статистично значущою (р=0,642). Хоча позитивне вipуснe навантаження було бтьш поширеним у новонароджених, народжених вiд мamepiв з позитивним вipусним навантаженням, спостережувана pi-зниця також залишалася незначущою (p=0,978). Наше до^дження надало докази того, що дeмогpaфiчнi, iмунологiчнi та кл-шчш характеристики мamepiв з тфекщею гепатиту В не вiдiгpaвaли значно'1' ролi у вертикальнт пepeдaчi тфекцп новонародженим, а також mяжкосmi подальшо'1' тфекцп. Ми також припустили можлж-^ь того, що плацента виступае джерелом тфекцп при ВП. Поmpiбнe подальше лонгтудинальне до^дження з бшьшими pозмipaми вибipки, щоб показати mочнi предиктори пepeдaчi тфекцп вiд тфжованих мamepiв iхтм дimям.

Hepatitis B virus (HBV) is a serious global health issue, especially among Asian countries. Around 257 million people are infected by HBV, worldwide [1]. HBV infection can present as an acute, chronic or even fulminant hepatitis. Hepatocellular carcinoma and liver cirrhosis can occur as long-term outcomes of HBV infection, as well [2]. One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT) [3]. Despite providing early vaccination as well as HBV immunoglobulin in order to prevent

neonates from developing chronic infection, immu-noprophylaxis fail to inhibit HBV infection in up to 1-10% of infants [4, 5, 6, 7, 8]. Currently, there is no definite explanation for this failure, meanwhile it is assumed that it can be attributable to the high maternal viral load leading to intra-uterine infection ,or just the absence of adequate response in neonates who receive the vaccine [7, 9].The neonates infected through VT have a 90% risk of developing chronic infection which is mostly due to the immune response of the children compared with adults [10].

Intrauterine transmission (IUT) of HBV is the main route of VT (13-44%), which is defined as all sorts of transmission happening prior to the onset of labor. Some of the suggested mechanisms for IUT are placental infection, transplacental leakage, germline transmission, and transmission by peripheral blood mononuclear cells. Other means of VT include intrapartum and breastfeeding transmission [11, 12]. There are several studies investigating the risk factors of VT. It has been reported that factors like vaginal delivery [13], prolonged labor [14], and amniocentesis [15] can play a major role in VT. On the other hand, HBV viral factors such as HBV preS/S gene mutations and Serum HBV-DNA level have been indicated as reliable markers for predicting VT [16, 17, 18, 19]. Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process completely. On the other hand, as genetic factors are among the important factors affecting VT of HBV, and there was no such study evaluating VT and its risk factors in eastern Iran. We conducted this study aiming at investigating VT mechanism and risk factors in this region.

MATERIALS AND METHODS OF RESEARCH

The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-Al-Momenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study, all pregnant women with HBV referred to the hospital for delivery during the above period were included in the study. Among them, pregnant mothers with various underlying diseases, hepatitis C, immunodeficiency, and/or family history of hereditary immunodeficiency diseases and patients with a variety of fetal abnormalities or fetal death were excluded. Finally, 43 infants born to HBS antigen positive mothers were evaluated. General characteristics, including maternal age, gravidity, and parity, as well as the date of delivery were

documented. This project was approved by the ethics committee of Zabol University of Medical Sciences, and informed consent was obtained from patients prior to their enrollment.

Laboratory Investigation

After obtaining the patients' informed consent, a 5-cc blood sample was taken from each of them. All samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA).

The commercial enzyme immunoassay kits used were as follows: HBsAg and anti-HBs (Hepano-sticka Biomerieux, Boxtel, The Netherlands), anti-HBc (Dia.Pro Diagnostic BioProbes, Milan, Italy), anti-HCV (Biorad, Segrate, Italy). Liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Alkaline Phosphatase (ALP)] were also determined in all of the patients. To investigate latent hepatitis infection, HBV-DNA was extracted from all samples using the DNA extraction kit, High Pure Viral Nucleic Acid kit (Roche Diagnostics GmbH, Mannheim, Germany). Then HBV-DNA was determined quantitatively by real-time PCR using the artus HBV RG PCR kit (QIAGEN, Hamburg, Germany) on the Rotor-Gene 3000 realtime thermal cycler (Corbett Research, Sydney, Australia). The analytical detection limit of this kit was 20 IU/ml.

DNA Amplification

For all samples, Nested PCR was performed with surface antigen primers including external (S1, S2) and Internal (S6, S7) by Taq DNA Polymerase kit. The sequence and size of the primers are given in the figure below (Figure). The second-round PCR products were transferred to 1% gel electrophoresis. Their positive sequence samples were determined, and their nucleotide sequence was determined bilaterally by ABI sequencer 3130Xi, and the mutations in this fragment were identified.

Primer Gene Seq 5' to 3' Base

S1 Surface 5-CCTGCTGGTGGCTCCAGTTC-3' 20

S2 Surface 5 -CCACAATTCKTTGACATACTTTCCA-3' 25

S6 Surface 5-GCACACGGAATTCCGAGGACTGGGGACCCTG-3' 31

S7 Surface 5'-GACACCAAGCTTGGTTAGGGTTTAAATGTATACC-3' 34

Sequence and size of hepatitis B surface gene primers

22/ Том XXVII/1 125

Statistical analysis

The correlation between categorical variables was estimated using the Spearmen correlation coefficient. All statistical analyzes were performed using SPSS version 22 software. Age, Liver enzyme, and other laboratory and demographic information were expressed as mean ± standard deviation. The Chi-square test and Fisher's exact test were used to compare categorical data. The significance level was set at p<0.05. The prognostic value was expressed as odds ratios (OR) and corresponding 95% confidence interval (CI).

RESULTS AND DISCUSSION

Totally 43 infants of HBS antigen positive mothers were investigated 25 (58.1%) of whom were boys and mean (SD) age of them was 3.6 (2) months. The youngest and oldest infants were one and 10 months old, respectively. Mothers were in average 30.2±6.3 years old ranging from 14 to 44 years.

Of the studied mothers, 21 (71%) experienced normal vaginal delivery. Most of them were Iranian (74.4%) and the others were Afghan residents. Only 3 (9.7%) mothers reported a history of anti-viral treatment. Exclusive breast feeding was reported by 19 (44.4%) of mothers while 3 (9.7%) were feeding their neonates just by formula milk.

HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. The prevalence of HBs antigen positive children was 16 (37.2%), while 27 (62.8%) of them were HBS negative. HBe antibody and HBe antigen were positive in 28 (70%) and 1 (2.5) of the infants respectively.

Positive and negative HBs antigen newborns did not have any significant difference regarding gender (p=0.405), type of delivery (p=0.086), mother's nationality (p=0.130), history of antiviral therapy (p=0.452) and feeding type (p=0.338) (Table 1).

Table 1

Demographic and clinical characteristics of newborns with and without positive HBs antigen

Characteristics Infant's HBS Antigen

negative 1 positive

gender female number 10 8

% 37.40 50

male number 17 8

% 62.96 50

Type of delivery NVD number 18 9

% 81.82 56.25

Cesarean number 4 7

% 18.18 43.75

nationality Iranian number 18 14

% 66.67 87.5

Afghan number 9 2

% 33.33 12.5

History of Drug use no drug number 18 9

% 94.74 81.82

drug history number 1 2

% 5.26 18.18

Type of breast feeding breast milk number 14 5

% 70 45.45

replacement feeding number 2 1

% 100 9.09

mixed feeding number 4 5

% 20 45.45

P value

0.405

0.086

0.130

0.452

0.338

As demonstrated in table 2, frequencies of positive maternal HBe antibody among newborns with and without HBS antigen were 11 (68.7%) and 14 (58.33%) respectively (p=0.505). Corresponding figures for HBe antigen were zero and 2 (8.33%) respectively (p=0.508). There was no

significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065) (Table 3).

Table 2

Maternal immunological factors of the HBs antigen positive and negative infants

Maternal factors

Infant's HBS antigen

negative positive

number 10 5

% 41.67 31.25

number 14 11

iНе можете найти то, что вам нужно? Попробуйте сервис подбора литературы.

% 58.33 68.75

number 22 16

% 91.67 100

number 2 0

% 8.33 0

P value

Hbe Antibody

Hbe Antigen

negative

positive

negative

positive

0.505

0.508

Comparing demographic and biochemical factors between children with and without hepatitis B infection showed that just mean ALP was significantly higher among HBS antigen positive newborns (p=0.017). Other factors were not differed between the two groups (Table 4). As demonstrated

in table 5, crude and adjusted odds ratios for maternal positive HBe antigen were 0.60 (p=0.708) and 0.55 (p=0.662), respectively. The corresponding figures for positive HBe antibody in mothers were 1.57 (p=0.506) and 1.34 (p=0.702), respectively.

Table 3

Maternal characteristics of HBS antigen positive and HBS antigen negative children

Maternal factors Infant's HBsAg Number Mean Std. Deviation P value

Maternal age negative 18 30.65 6.47 0.532

positive 16 29.38 6.22

Duration of the infection negative 15 8.75 7.46 0.619

positive 13 11.77 11.32

AST negative 16 14.85 7.74 0.897

positive 13 14.15 4.77

ALT negative 16 3.85 2.30 0.685

positive 13 4.38 2.53

ALP negative 16 198 92 0.067

positive 13 144.92 52.06

22/ TOM XXVII/1

127

Table 4

Demographic and biochemical characteristics of the newborns with and without hepatitis B infection

Infant factors Infant's HBsAg Number Mean Std. Deviation P value

age negative 7 3.89 2.52 0.724

positive 6 3.17 .41

AST negative 13 31.75 14.94 0.659

positive 12 42.92 41.43

ALT negative 13 5.56 3.93 0.444

positive 12 6.75 4.09

ALP negative 13 180 88.5 0.017

positive 11 238.73 143.97

Viral load

Positive viral load was observed in 7 (16.28%) of neonates which was vanished after three months in all infants. Although the frequency of positive viral load at birth in neonates of positive HBe antibody mothers was higher than that among those with

negative HBe antibody mothers, this difference was not significant (p=0.819). Conversely, frequency of positive viral load at birth for neonates of positive HBe antigen was lower than that among those with negative antigen mothers, this difference was also non-significant (p=0.542) (Table 6).

Table 5

Crude and adjusted associations between maternal HBe antigen/antibody and hepatitis B infection vertical transmission

Maternal factors crude odds ratio (p value) 95% CI Adjusted* odds ratio (p value) 95% CI

Hbe antigen 0.60 (0.708) 0-8 0.55 (0.662) 0-7.55

Hbe antibody 1.57 (0.506) 0.41- 5.96 1.34 (0.702) 0.30-5.92

Note: Controlling for the effect of maternal nationality and type of delivery

Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more often than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered

from positive viral load mothers, the observed difference also remained non-significant (p=0.978). Crude and adjusted odds ratios for having positive HBS antigen or positive viral load at birth were also non-significant (Table 7).

Table 6

Neonatal viral load based on the immunological characteristics of mother

Maternal HBe antibody p value Maternal HBe antigen p value

negative positive negative positive

Viral load negative no 13 21 0.819 32 2 0.542

at birth

% 86.67 84 84.21 100

positive no 2 4 6 0

% 13.33 16 15.79 0

Total no 15 25 38 2

% 100 100 100 100

Table 7

Maternal viral load and its association with hepatitis B infection at birth

maternal viral load P value Crude OR (p value) 95% CI Adjusted* OR (p value) 95% CI

Negative no (%) Positive no (%)

Neonatal Negative 17(56.67) 2(40) 0.642 1 1

HBS (n=19)

antigen

Positive 13(43.33) 3(60) 1.85(0.489) 0.32-10.48 1.70 (0.577) 0.26- 11.10

(n=16)

Neonatal Negative 31(83.78) 5(83.33) 0.978 1 1

Viral load (n=36)

Positive 6(16.22) 1(16.67) 1.03(0.978) 0.10- 10.49 0.89 (0.922) 0.08- 9.32

(n=7)

Notes: OR - Odds ratio, CI - confidence interval, Controlling for the effect of maternal nationality and type of delivery.

Mean liver enzymes of the HBS antigen positive newborns were the same among those delivered from mothers with negative and positive viral load. That was the case for neonates of mothers with positive and negative HBe antibody, as well (Table 8).

Finally, we did not find any evidence of mutation in the S gene of the HBV which causes considerable changes in the a determinant area of HBS antigen.

We found that hepatitis B infection was vertically transferred from carrier mothers with positive HBe antigen the same as those with negative HBe antigen. Although having HBe antigen, increased the risk of developing hepatitis B infection in the newborn (18%), this association was not statistically significant.

Table 8

Severity of the newborn infection (HBS antigen positive neonates) based on the maternal factors

Maternal factors Newborn liver enzymes

AST ALT ALP

Mean (SD) Mean (SD) Mean (SD)

Viral load negative 47(44.54) 6.80 (4.47) 249 (158)

Positive 22.50(4.95) 6.50 (2.12) 194 (46.67)

P value 0.451 0.930 0.722

HBe antibody negative 48.80 (65.26) 7.60 (5.59) 203 (29)

Positive 38.71 (16) 6.14 (2.97) 259 (181)

P value 0.290 0.568 0.635

On the other hand, mothers with positive HBe antibody had transferred hepatitis B infection to their newborns the same as those with negative HBe antibody indicating that although positive maternal HBe antibody caused approximately 60% increased risk of hepatitis B vertical transmission, the observed association was also not significant in our study. Meanwhile, Boucheron et al. in their recent systematic review and meta-analysis indicated that a positive HBe Ag test can predict vertical transmission in spite of infant immunoprophylaxis with a

sensitivity of 99.5% and a specificity of 62.2%.That was not consistent with our findings which showed that vertical HBV transmission was similar in mothers with and without HBe antigen .However, they mentioned that they could not evaluate the effects of different HBV genotypes on the performance of HBe antigen [20]. Dwivedi et al reported that mother to child transmission of hepatitis B infection is directly associated with the hepatitis B virus replicative status of mother. They found that 76.4% of positive HBe antigen mothers compared

22/ TOM XXVII/1

129

with 23.6% of HBe negative mothers transmitted hepatitis B infection to their neonates. That was not in keeping with our findings which showed that vertical HBV transmission was similar in mothers with and without HBe antigen [21]. Therefore, in contrast to the recent evidences reporting high frequency of maternal HBe antigen as the main cause of HBV vertical transmission in the endemic regions [22], it seems that in the study area other factors should also be considered as the routes of transmission.

We also observed that hepatitis B infection vertical transmission occurred with the same rate after vaginal or cesarean delivery. However, previous researches reported the influence of delivery mode on HBV transmission with controversies [23]. Deng et al. in a more recent study indicated that cesarean section might decrease the vertical transmission of HBV in pregnant women with HBV DNA>107 copies/mL [24]. Moreover, mothers of different age or different treatment durations had no different chance of hepatitis B infection vertical transmission.

In addition, Iranian mothers showed the same rate of infection transmission compared to Afghan mothers. Although refugees and immigrants are expected to be more suspected to transmit infection due to low quality of care, it seems that low sample size of Afghan participants makes our finding prone to bias. Investigating the viral load in neonates at birth showed that mothers with positive HBe antigen compared to those with negative antigen delivered newborns with similar viral load rates. In addition, viral load was the same in neonates of mothers with positive or negative HBe antibody indicating that HBe antigen or antibody cannot predict the degree of viral load in neonates. We also observed that although having a positive viral load during pregnancy was associated with more than two folds increased risk of HBV infection at birth, the observed association was not statistically significant. It demonstrates that viral load status of pregnant mothers with hepatitis B infection, cannot be a reliable predictor of neonatal infection at birth. Meanwhile, Boucheron et al. reported that HBV

DNA levels higher than f 5 30 logi0 IU/mL increases the risk of vertical transmission [20]. It should be noted that some neonates with positive viral load were delivered from mothers with negative viral loads indicating some other probable sources of infection such as placental infection. Chen et al. in their study evaluated individual cell layers of placenta and found HBV DNA, HBsAg as well as HBcAg in these cells. Their results could be indicative of the presence of infection in placenta. They also reported this type of infection in 31% of their patients as the main cause of vertical transmission [25]. In our study, viral load was vanished during the first three months of life which was much shorter than that reported in the previous literature. These differences might be due to the fact that none of our mothers with hepatitis B infection had S mutant. Similar liver enzymes of mothers giving birth to infants with and without hepatitis B infection indicates that probably liver function during pregnancy cannot be a predictor for hepatitis B infection vertical transfer.

iНе можете найти то, что вам нужно? Попробуйте сервис подбора литературы.

In the present study, we found that mothers with positive viral load or positive HBe antibody, delivered infected newborns with the same levels of liver enzymes indicating that maternal factors did not affect the severity of the hepatitis B infection in their newborns.

In conclusion, our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility of placenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their children.

Funding. This research received no external funding.

Conflict of interests. The authors declare no conflict of interest.

references

1. World Health Organization. Hepatitis B. (updated July 2016). 2016. Available from: http://www.who.int/mediacentre/factsheets/fs204/en/

2. Naghavi M, Wang HD, Lozano R, et al. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 19902013: a systematic analysis for the Global Burden

of Disease Study 2013. Lancet. 2015;385:117-71. doi: https://doi.org/10.1016/S0140-6736(14)61682-2

3. Chen HL, Zha ML, Cai JY, Qin G. Maternal viral load and hepatitis B virus mother-to-child transmission risk: A systematic review and meta-analysis. Hepatology Research. 2018 Sep;48(10):788-801. doi: https://doi.org/10.1111/hepr.13072

4. Wang Z, Zhang J, Yang H, Li X, Wen S, Guo Y, et al. Quantitative analysis of HBV DNA level and HBeAg titer in hepatitis B surface antigen positive mothers and their babies: HBeAg passage through the placenta and the rate of decay in babies. J Med Virol. 2003;71:360e6. doi: https://doi.org/10.1002/jmv.10493

5. Yang YJ, Liu CC, Chen TJ, Lee MF, Chen SH, Shih HH, et al. Role of hepatitis B immunoglobulin in infants born to hepatitis B e antigen-negative carrier mothers in Taiwan. Pediatr Infect Dis J. 2003;22:584e8. doi: https://doi.org/10.1097/01.inf.0000073123.93220.a8

6. Song YM, Sung J, Yang S, Choe YH, Chang YS, Park WS. Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus. Eur J Pediatr. 2007;166:813e8.

doi: https://doi.org/10.1007/s00431-006-0327-5

7. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Viro-logic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat. 2012;19:e18e25.

doi: https://doi.org/10.1111/j.1365-2893.2011.01492.x

8. Lee LY, Chan SM, Ong C, Aw MM, Wong F, Saw S, et al. Comparing monovalent and combination hepatitis B vaccine outcomes in children delivered by mothers with chronic hepatitis B. J Paediatr Child Health. 2019;55:327e32. doi: https://doi.org/10.1111/jpc.14194

9. Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of mother-to-child transmission of hepatitis B virus: propositions and challenges. J Clin Virol. 2016;77:32-9. doi: https://doi.org/10.1016/jjcv.2016.02.003

10. del Canho R, Grosheide PM, Schalm SW, de Vries RR,Heijtink RA. Failure of neonatal hepatitis B vaccination: the role of HBV-DNA levels in hepatitis B carrier mothers and HLA antigens in neonates. J Hepatol. 1994;20:483e6.

doi: https://doi.org/10.1016/S0168-8278(05)80494-5

11. Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of mother-to-child transmission of hepatitis B virus: propositions and challenges. Journal of Clinical Virology. 2016 Apr 1;77:32-9.

doi: https://doi.org/10.1016/jjcv.2016.02.003

12. Yu M, Jiang Q, Gu X, Ju L, Ji Y, Wu K, et al. Correlation between vertical transmission of hepatitis B virus and the expression of HBsAg in ovarian follicles and placenta. PLoS One 2013;8:e54246. doi: https://doi.org/10.1371/journal.pone.0054246

13. Ma L, Alla NR, Li X, Mynbaev OA, Shi Z. Mother-to-child transmission of HBV:review of current clinical management and prevention strategies. Rev Med Virol. 2014;24:396-406.

doi: https://doi.org/10.1002/rmv.1801

14. Yang J, Zeng XM, Men YL, Zhao LS. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus - a systematic review. Virol J. 2008;28:5.

doi: https://doi.org/10.1186/1743-422X-5-100

15. Wong VC, Lee AK, Ip HM. Transmission of hepatitis B antigens from symptom free carrier mothers to the fetus and the infant. Br J Obstet Gynaecol 1980;87:958-65. doi: https://doi.org/10.1111/j.1471-0528.1980.tb04458.x

16. Yi W, Pan CQ, Hao J, et al. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol. 2014;60:523-9. doi: https://doi.org/10.1016/j.jhep.2013.11.008

17. Gao Y, Guo J, Zhang F, et al. Evaluation of neonatal Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in HBV intrauterine transmission susceptibility. Epidemiol Infect. 2015;143:1868-75. doi: https://doi.org/10.1017/S0950268814002921

18. Yin Y, Zhang P, Tan Z, Zhou J, Wu L, Hou H. The association of pre-S/S gene mutations and hepatitis b virus vertical transmission. Hepat Mon. 2016;16:e32160. doi: https://doi.org/10.5812/hepatmon.32160

19. Zhang Z, Li A, Xiao X. Risk factors for intrau-terine infection with hepatitis B virus. Int J Gynaecol Obstet. 2014;125:158-61.

doi: https://doi.org/10.1016/j.ijgo.2013.10.028

20. Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013;59:24-30.

doi: https://doi.org/10.1016/jjhep.2013.02.015

21. Boucheron P, Lu Y, Yoshida K, Zhao T, Funk AL, Lunel-Fabiani F, et al. Accuracy of HBeAg to identify pregnant women at risk of transmitting hepatitis B virus to their neonates: a systematic review and meta-analysis. The Lancet Infectious Diseases. 2021 Jan 1;21(1):85-96. doi: https://doi.org/10.1016/S1473-3099(20)30593-4

22. Dwivedi M, Misra SP, Misra V, Pandey A, Pant S, Singh R, Verma M. Seroprevalence of hepatitis B infection during pregnancy and risk of perinatal transmission. Indian Journal of Gastroenterology. 2011 Mar;30(2):66-71.

doi: https://doi.org/10.1007/s12664-011-0083-y

23. Teo E-K, Lok AS. Epidemiology, transmission and prevention of hepatitis B virus infection. In: Rose BD, editor. uptodate 2010.

24. Wei J, Xue S, Zhang J, Wang S, Wang B. Study of the relationship in pregnant women between hepatitis B markers and a placenta positive for hepatitis B surface antigen. Journal of perinatal medicine. 2015;43(2):191-9. doi: https://doi.org/10.1515/jpm-2014-0056

25. Deng TK, Yang P, Liu X, Wang D, Luo H, Zhou J, Xiao X. Influence of different delivery modes and HBV DNA titers on mother-to-child transmission of hepatitis B. Clinics and Research in Hepatology and Gastroenterology. 2020 Oct 14.

doi: https://doi.org/10.1016/j.clinre.2020.08.017

26. Chen Y, Wang L, Xu Y, Liu X, Li S, Qian Q, et al. Role of maternal viremia and placental infection in hepatitis B virus intrauterine transmission. Microbes Infect. 2013;15:409-15.

doi: https://doi.org/10.1016/j.micinf.2013.02.008

Crana Hagmmga go pega^ii' 08.09.2021

22/ TOM XXVII/1

131

i Надоели баннеры? Вы всегда можете отключить рекламу.