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1.  Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus 
Many clinicians and hepatitis B virus (HBV)-infected pregnant women prefer elective caesarean section (ECS) to prevent mother-to-child transmission of HBV, since some studies found higher transmission of HBV in infants born by vaginal delivery (VD) than by cesarean section. However, other studies showed that ECS does not reduce the risk of being infected with HBV in infants. In this study, we aimed to clarify whether ECS may reduce the risk of mother-to-child transmission of HBV.
Totally 546 children (1–7-year-old) born to 544 HBsAg-positive mothers from 15 cities and rural areas across Jiangsu Province, China, were enrolled. Of these children, 137 (2 pairs of twins) were born to HBeAg-positive mothers; 285 were delivered by ECS and 261 others by VD (one pair of twin in each group). HBV serologic markers were tested by enzyme or microparticle immunoassay.
The maternal and gestational ages, maternal HBeAg-positive rates, and children’s ages, gender ratios, hepatitis B vaccine coverage and administrations of HBIG were comparable between ECS and VD groups (all p >0.05). The overall prevalence of HBsAg in the 546 children was 2.4%, with 2.5% (7/285) and 2.3% (6/261) in those born by ECS and VD respectively (p = 0.904). Further comparison of chronic HBV infection in the 137 children of HBeAg-positive mothers showed that the HBsAg-positive rates in ECS and VD groups were 10.3% (7/68) and 8.7% (6/69) respectively (p = 0.750), while the mothers had similar HBV DNA levels (2.38 × 106 vs. 2.35 × 106 IU/ml, p = 0.586). Additionally, the overall rate of anti-HBs ≥10 mIU/ml in the children was 71.6%, with 72.3% and 70.9% in those born by ECS and VD respectively (p = 0.717).
With the recommended immunoprophylaxis against hepatitis B, ECS does not reduce the risk of mother-to-child transmission of HBV. Therefore, ECS should not be used in HBsAg-positive pregnant women to prevent mother-to-child transmission of HBV.
PMCID: PMC3664615  PMID: 23706093
Hepatitis B virus; Mother-to-child transmission; Vaginal delivery; Caesarean section
2.  Breastfeeding Is Not a Risk Factor for Mother-to-Child Transmission of Hepatitis B Virus 
PLoS ONE  2013;8(1):e55303.
Many clinicians do not encourage breastfeeding in hepatitis B virus (HBV) carriers, since HBV DNA can be detected in breast milk and breast lesions may increase exposure of infants to HBV. The aim of this study was to determine whether breastfeeding may add risk for perinatal HBV transmission.
Methodology/Principal Findings
Totally 546 children (1–7-year-old) of 544 HBV-infected mothers were investigated, with 397 breastfed and 149 formula-fed; 137 were born to HBeAg-positive mothers. All children had been vaccinated against hepatitis B but only 53.3% received hepatitis B immune globulin (HBIG). The overall prevalence of HBsAg+, HBsAg−/anti-HBc+, and anti-HBs (≥10 mIU/ml) in children was 2.4%, 3.1%, and 71.6% respectively. The HBsAg prevalence in breast- and formula-fed children was 1.5% and 4.7% respectively (P = 0.063); the difference was likely due to the higher mothers' HBeAg-positive rate in formula-fed group (formula-fed 49.0% vs. breastfed 15.9%, P<0.001). Further logistic regression analyses showed that breastfeeding was not associated with the HBV infection in the children, adjusting for the effect of maternal HBeAg status and other factors different between the two groups.
Under the recommended prophylaxis, breastfeeding is not a risk factor for mother-to-child transmission of HBV. Therefore, clinicians should encourage HBV-infected mothers to breastfeed their infants.
PMCID: PMC3557270  PMID: 23383145
3.  Active-passive Immunization Effectiveness Against Hepatitis B Virus in Children Born to HBsAg Positive Mothers in Amol, North of Iran 
Oman Medical Journal  2011;26(6):399-403.
HBV infection is a contagious disease that may transmit vertically from mothers to their neonates or horizontally by blood products and body secretions. Over 50% of Iranian carriers have contracted the infection perinatally, making this the most likely route of transmission of HBV in Iran. This study assesses the serologic markers of HBV in children born to HBsAg positive mothers who received HBIG and 3 doses of HBV vaccine.
To evaluate the effectiveness of vaccination against HBV, a study was conducted on 95 Children, born to hepatitis B surface antigen (HBsAg)-positive mothers, who had received Hepatitis B Immune Globulin and HBV vaccines during 2004-2008. All children were tested for the presence of HBsAg, anti-HBs and anti-HB core antigen (anti-HBc).
Among an estimated 30000 pregnant women during the five year study, about 130 (0.42%) were HBV carriers. Ninety-five children from these mothers were enrolled in this study. Only one child (1.1%) was HBsAg positive, while 88.4% of children were Anti-HBs Positive. Eleven children (11.6%) were exposed to HBV as shown by the presence of anti-HBc. A significant difference was observed between the children’s age and Anti-HBs (p=0.0001).
Passive-active immunoprophylaxis of high risk babies was highly efficacious in preventing perinatal transmission of the HBV carrier state. Also, evaluation of serologic markers in HBV infected people is important for designing the strategies for disease control.
PMCID: PMC3251203  PMID: 22253947
Children; HBsAg positive mothers; Hepatitis B Vaccine; Hepatitis B Immunoglobulin; Anti-HBc; Anti-HBs
4.  Hepatitis B surface antigen prevalence among 12 393 rural women of childbearing age in Hainan Province, China: a cross-sectional study 
Virology Journal  2013;10:25.
Hepatitis B virus (HBV) infection is highly endemic in China and it threats human health seriously. The hepatitis B surface antigen (HBsAg) prevalence among women of childbearing age plays an important role in mother to child transmission of HBV, as 30% ~50% of chronic carriers can be attributed to maternal-infantile transmission. However, there are few studies which have reported on the prevalence of HBsAg among women of childbearing age in China. This study aimed to determine the prevalence of HBsAg and its associated risk factors among rural women of childbearing age in Hainan, which is the highest hepatitis B virus endemic province in China.
A cross-sectional, population-based study, which included 12393 rural women aged 15 ~ 49 years, enrolled by a multistage stratified cluster sampling, was carried out in Hainan province, China, from November 2007 to December 2008. Blood samples were obtained from each study participant, and screened for HBsAg.
The overall HBsAg prevalence of childbearing age women was 9.51%. Risk factors for HBsAg positivity among rural women were: lower education level (OR=1.206), lower family monthly income (OR=1.233), having an HBsAg-positive family member (OR=1.300), without an immunization history (OR=1.243), tattooing (OR=1.190), body piercing (OR=1.293), vaginoscopy history (OR=1.103) and history of induced abortion (OR=1.142).
There is a high HBsAg seroprevalence rate among rural women of childbearing age in Hainan province. Hence, it is necessary to take preventive measures to reduce the seroprevalence of HBsAg and to control its associated risk factors.
PMCID: PMC3626832  PMID: 23332007
China; Women of childbearing age; Hepatitis B surface antigen; Seroprevalence; Risk factors
5.  Analysis of residual perinatal transmission of hepatitis B virus (HBV) and of genetic variants in human immunodeficiency virus and HBV co-infected women and their offspring 
Despite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women.
We assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children.
Study design
HIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4–6 months. HBV diversity within each HBV-infected mother-infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products.
Among 3,312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4–6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother-infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg “a” determinant, and four were infected with wild-type HBV present in highly viremic mothers.
HBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.
PMCID: PMC3872003  PMID: 23916828
HBs antigen variants; Hepatitis B vaccine failure; HIV pregnant women; mother-to-child transmission; Thailand
6.  Chronic HBV infection among pregnant women and their infants in Shenyang, China 
Virology Journal  2013;10:17.
The main transmission route of the hepatitis B virus (HBV) is mother to child transmission and contributes significantly to chronic HBV infection. Even though immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine is administrated to neonates whose mothers are hepatitis B surface antigen (HBsAg) positive, about 10% of the neonates suffer from HBV infection in their early life.
To survey chronic HBV infection among pregnant women and their infants and analyze the reason for immunoprophylaxis failure.
Serum HBsAg was tested in all pregnant women. HBVDNA and other serum HBV markers including hepatitis B e antigen (HBeAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) were tested among HBsAg positive pregnant women. All infants whose mothers were HBsAg positive were vaccinated with a standard immunoprophylaxis. Serum HBV markers and HBVDNA were tested among these infants at 7 months of age. HBV genotypes were analyzed among the infants and pregnant women who were HBVDNA positive.
The prevalence of HBsAg, anti-HBc and anti-HBs among 4,536 pregnant women was 5.49%, 29.65% and 58.55%, respectively. The prevalence of HBsAg, anti-HBc and anti-HBs among pregnant women older than 20 years of age was significantly different compared to pregnant women younger than 20 years of age (4.54, 5.69 and 0.61 times, prevalence older vs. younger, respectively. P<0.05, 0.01, 0.05, respectively). Among 249 HBsAg positive pregnant women, 167 (67.07%) were HBeAg positive, 204 (81.93%) were HBVDNA positive and only 37 (14.86%) had HBVDNA >107 IU/ml. Among the infants whose mothers were HBsAg positive, 214 (85.94%) infants were anti-HBs positive. There were 12 (4.82%) infants who were HBsAg and HBVDNA positive, and all 12 of these infants mothers were HBeAg positive and had HBVDNA >107 IU/ml. Genotypes B and C were present among 165 pregnant women and genotype C was present in 85 pregnant women. There were 12 infants who were HBsAg positive and had the same HBV genotypes as their mothers. There was a significant difference in genotypes between the pregnant women whose infants were infected with HBV compared to those without HBV infection (P < 0.05).
There was a significant decline in HBsAg prevalence among pregnant women and their infants in Shenyang. Genotype C might be a risk factor for mother to child transmission of HBV.
PMCID: PMC3568011  PMID: 23294983
HBV; Infection; Pregnancy; Mother to child transmission
7.  Chronic hepatitis B in pregnancy: unique challenges and opportunities 
Chronic hepatitis B (CHB) affects 350 million individuals worldwide. Perinatal transmission leads to high rates of chronic infection and complications, including cirrhosis and hepatocellular carcinoma. It is important to recognize and appropriately treat CHB in pregnancy, thereby reducing the risk of neonatal transmission and HBV-associated morbidity and mortality. Screening for CHB is recommended in all pregnant mothers as is universal vaccination of infants with hepatitis B virus (HBV) vaccine with or without hepatitis B immunoglobulin (HBIG). This has resulted in a lower incidence of HBsAg seropositivity and HCC in regions where universal infant vaccination has been endorsed. Mode of delivery and breastfeeding do not appear to affect HBV transmission rates based on available data. Overall, CHB does not increase perinatal maternal-fetal mortality. Administration of oral antiviral therapy during the third trimester to HBsAg-positive mothers with HBV DNA≥7 log IU/mL may be useful in preventing breakthrough infection. Treatment may be considered earlier in pregnancy for persistently active liver disease shown by high ALT, HBV DNA levels and/or significant hepatic fibrosis. Lamivudine, tenofovir and telbivudine are safe and effective and are the agents of choice in pregnancy. However, further clinical studies are necessary to elucidate the role of antiviral therapy in the pregnant HBV carrier.
PMCID: PMC3304622  PMID: 21494071
Hepatitis B; Pregnancy; Prevention; Transmission; Antivirals
8.  Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China. 
Gut  1996;38(Suppl 2):S39-S42.
China has one of the highest rates of hepatitis B virus (HBV) endemicity in the world. In a survey of five provinces, the overall HBV infection rate in the general population was found to be 42.6%, with 10.3% testing positive for hepatitis B surface antigen (HBsAg). Higher rates were found in rural than in urban areas. The prevalence of HBsAg among children under 1 year of age is quite low but increases rapidly thereafter, reaching a peak among 5 to 9 year olds. The pattern of age distribution suggests that horizontal transmission is an important route of HBV infection during early childhood, and the proportion of chronic HBsAg carriage attributable to perinatal transmission has been estimated at only 13-20%. Contact with infected family members probably accounts for much of the horizontal transmission in children. In a nationwide survey, 27.2% of families were found to have one or more HBsAg positive members and a strong tendency for family clustering has been identified. The strategy for prevention of HBV infection includes vaccination of all newborns, whether their mothers are HBsAg positive or negative, together with vaccination of high risk populations, and improved control measures in clinics and blood transfusion centres.
PMCID: PMC1398042  PMID: 8786052
9.  Passive Immunization against Exposure to Hepatitis B Virus in the Military: Potential and Possibilities 
The value of standard γ-globulin with a low titer of antibody to hepatitis B surface antigen (anti-HBs) vs hepatitis B immune globulin (HBIG) in prevention of icteric hepatitis B in the military is unclear. Although recent studies have shown a decrease in icteric hepatitis after administration of both types of γ-globulin in populations where acquisition of hepatitis B virus (HBV) is most likely the result of nonparenteral transmission, the data pertaining to parenteral exposure suggest that HBIG delays the incubation period of HBV and decreases the development of passive-active immunity. Since no studies have demonstrated efficacy of standard γ-globulin or HBIG in a drug-using population where multiple HBV exposures are likely, the results observed in most trials are not comparable to hepatitis B associated with drug abuse in the military. Therefore, before a recommendation for use of routine γ-globulin or HBIG can be made for drug-related hepatitis in the military, efficacy of standard γ-globulin and/or HBIG should be demonstrated in this population.
PMCID: PMC2595364  PMID: 60830
10.  Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection 
AIM: To evaluate the effects of tenofovir disoproxil fumarate (TDF) use during late pregnancy to reduce hepatitis B virus (HBV) transmission in highly viremic mothers.
METHODS: This retrospective study included 45 pregnant patients with hepatitis B e antigen (+) chronic hepatitis B and HBV DNA levels > 107 copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation (n = 21). Untreated pregnant patients served as controls (n = 24). All infants received 200 IU of hepatitis B immune globulin (HBIG) within 24 h postpartum and 20 μg of recombinant HBV vaccine at 4, 8, and 24 wk. Perinatal transmission rate was determined by hepatitis B surface antigen and HBV DNA results in infants at week 28.
RESULTS: At week 28, none of the infants of TDF-treated mothers had immunoprophylaxis failure, whereas 2 (8.3 %) of the infants of control mothers had immunoprophylaxis failure (P = 0.022). There were no differences between the groups in terms of adverse events in mothers or congenital deformities, gestational age, height, or weight in infants. At postpartum week 28, significantly more TDF-treated mothers had levels of HBV DNA < 250 copies/mL and normalized alanine aminotransferase compared with controls (62% vs none, P < 0.001; 82% vs 61%, P = 0.012, respectively).
CONCLUSION: TDF therapy during the second or third trimester reduced perinatal transmission rates of HBV and no adverse events were observed in mothers or infants.
PMCID: PMC3882411  PMID: 24409065
Hepatitis B; Tenofovir; Reverse transcriptase inhibitors; Vertical transmission; Chronic
11.  Prophylaxis of hepatitis B infection in solid organ transplant recipients 
Rates of transmission of hepatitis B virus (HBV) infection from organ donors with HBV markers to recipients along with reactivation of HBV during immunosuppression following transplantation have fallen significantly with the advent of hepatitis B immune globulin (HBIg) and effective antiviral therapy. Although the availability of potent antiviral agents and HBIg has highly impacted the survival rate of HBV-infected patients after transplantation, the high cost associated with this practice represents a major financial burden. The availability of potent antivirals with high genetic barrier to resistance and minimal side effects have made it possible to recommend an HBIg-free prophylactic regimen in selected patients with low viral burden prior to transplant. Significant developments over the last two decades in the understanding and treatment of HBV infection necessitate a re-appraisal of the guidelines for prophylaxis of HBV infection in solid organ transplant recipients.
PMCID: PMC3667476  PMID: 23814610
HBV prophylaxis; HBV recurrence; HBV reinfection; solid organ transplant
12.  Strategy for vaccination against hepatitis B in areas with high endemicity: focus on Korea. 
Gut  1996;38(Suppl 2):S63-S66.
Hepatitis B vaccination strategies may vary from country to country depending on hepatitis B virus (HBV) endemicity, predominant modes of infection, age of infection, and health care resources. In areas with high endemicity like Korea, transmission of virus from carrier mothers to infants during the perinatal period, and from other horizontal sources to infants and children, account for most cases of HBV infection. The consequences of HBV infection at an early age are serious, as more than 70% remain chronic carriers of the virus. These chronic carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing other serious diseases, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Theoretically, therefore, routine infant immunisation supplemented with prenatal screening of pregnant women for HBsAg or HBeAg and mass immunisation of children is the appropriate strategy for control of hepatitis B in these countries. To prevent primary liver cancer associated with HBV infection, however, immunisation of adults at high risk would also be prudent. Mandatory vaccination of all neonates is recommended in highly endemic areas, together with hepatitis B immune globulin in babies born to HBsAg carrier mothers.
PMCID: PMC1398045  PMID: 8786058
13.  Hepatitis B in pregnancy. 
Western Journal of Medicine  1989;150(6):668-674.
Chronic infection with the hepatitis B virus can result in the development of serious liver disease such as chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. Vertical transmission from infected mothers to infants is thought to be partially responsible for the high prevalence of infection in certain high-risk groups. Immunoprophylaxis using hepatitis B vaccine and hepatitis immune globulin has been highly effective in decreasing the probability of chronic hepatitis B virus infection in infants with exposure. Previously, the Centers for Disease Control recommended screening pregnant women considered at high risk of hepatitis B infection to detect newborns who would benefit from postnatal immunizations directed at preventing the HBV carrier state. Because of the poor sensitivity of high-risk criteria in distinguishing pregnant women who harbor the hepatitis B virus, these recommendations have recently been revised to call for the routine screening of all pregnant women in the United States.
PMCID: PMC1026704  PMID: 2665319
14.  An economic analysis of premarriage prevention of hepatitis B transmission in Iran 
To assess the economic aspects of HBV (hepatitis B virus) transmission prevention for premarriage individuals in a country with cultural backgrounds like Iran and intermediate endemicity of HBV infection.
A cost-effectiveness analysis model was used from the health care system and society perspectives. The effectiveness was defined as the number of chronic HBV infections averted owing to one of the following strategies:
1) HBsAg screening to find those would-be couples one of whom is HBsAg positive and putting seronegative subjects on a protection protocol comprising HBV vaccination, single dose HBIG and condom protection.
2) HBsAg screening as above, in addition to performing HBcAb screening in the HBsAg negative spouses of the HBsAg positive persons and giving the protocol only to HBcAb negative ones.
Sensitivity and threshold analyses were conducted.
The cost of each chronic infection averted was 202$ and 197$ for the strategies 1 and 2, respectively. Sensitivity analysis showed that strategy 2 was always slightly cheaper than strategy 1. The discounted threshold value for the lifetime costs of chronic liver disease, above which the model was cost saving was 2818$ in strategy 1 and 2747$ in strategy 2.
Though premarriage prevention of HBV transmission in the countries with cultural backgrounds similar to Iran seems cost saving, further studies determining precise costs of HBV infection in Iran can lead to a better analysis.
PMCID: PMC517713  PMID: 15347430
15.  Hepatitis B in pregnancy 
Frontline Gastroenterology  2013;5(2):111-117.
Vertical transmission of the hepatitis B virus (HBV) is the commonest mode of infection and can be prevented with immunoprophylaxis of the infant and antiviral therapy in the mother. Our aim was to review a cohort of subjects with HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA levels that required treatment to prevent transmission, and to review the management of mothers and infants.
A retrospective case-note review was conducted of all the HBV-infected pregnant women and their infants who attended the Newcastle obstetric services from 2007 to 2011.
There were 113 pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg) positive) during 2007–11. 71% of mothers were first diagnosed with HBV during pregnancy. The mothers were born in 28 different countries. 69% of mothers had an HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than 1.0×107 IU/mL so would be eligible for antiviral therapy to prevent transmission to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV requiring treatment. All infants born to HBeAg-positive mothers received hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a full HBV vaccination course. One infant born to an HBeAg-negative mother was hepatitis B surface antigen positive 1 year post-delivery.
One in six women had active HBV requiring treatment or high HBV-DNA levels that would benefit from antiviral treatment to reduce the transmission risk. HBIG was administered appropriately but completion of the vaccination course was suboptimal.
PMCID: PMC3963528
16.  Adherence to the screening program for HBV infection in pregnant women delivering in Greece 
Hepatitis B infection (HBV) is a major Public Health Problem.
Perinatal transmission can be prevented with the identification of HBsAg(+) women and administration of immunoprophylaxis to their newborns. A national prevention programme for HBV with universal screening of pregnant women and vaccination of infants is in effect since 1998 in Greece.
To evaluate adherence to the national guidelines, all women delivering in Greece between 17–30/03/03 were included in the study. Trained health professionals completed a questionnaire on demographic data, prenatal or perinatal screening for HBsAg and the implementation of appropriate immunoprophylaxis.
During the study period 3,760 women delivered. Prenatal screening for HBsAg was documented in 91.3%. Greek women were more likely to have had prenatal testing. HBsAg prevalence was 2.89% (95%CI 2.3–3.4%). Higher prevalence of HBV-infection was noted in immigrant women, especially those born in Albania (9.8%). Other risk factors associated with maternal HBsAg (+) included young maternal age and absence of prenatal testing. No prenatal or perinatal HBsAg testing was performed in 3.2% women. Delivering in public hospital and illiteracy were identifiable risk factors for never being tested. All newborns of identified HBsAg (+) mothers received appropriate immunoprophylaxis.
The prevalence of HBsAg in Greek pregnant women is low and comparable to other European countries. However, immigrant women composing almost 20% of our childbearing population, have significant higher prevalence rates. There are still women who never get tested. Universal vaccination against HBV at birth and reinforcement of perinatal testing of all women not prenatally tested should be discussed with Public Health Authorities.
PMCID: PMC1475591  PMID: 16681862
17.  Ante-natal screening for hepatitis B surface antigen: an appraisal of its value in a low prevalence area. 
Epidemiology and Infection  1996;117(1):121-131.
The costs and projected benefits of universal screening for hepatitis B virus (HBV) infection in pregnant women in East Anglia are calculated and compared with current practice. By adjusting data from West Midlands region for ethnicity, the prevalence of maternal hepatitis B surface-antigen (HBsAg) positivity in East Anglia is predicted to be 0.083% (1 in 1200). Published data on health risks of perinatal HBV infection and on immunisation efficacy are used to derive benefits of screening. The marginal direct cost of screening is identified from regional sources. Current clinical practice in East Anglia identifies 7 surface-antigen positive mothers per year, whereas 22 are expected. Routine antenatal screening in East Anglia would prevent 2.6 additional childhood carriers per year (compared with current practice), resulting in the prevention of 0.7 deaths per year occurring 40-50 years in the future. The direct cost per (undiscounted) life-year saved would be Pounds 2437, not including savings on treatment for chronic hepatitis B infection. Routine prenatal screening for maternal HBsAg should be introduced without delay and continue even if HBV vaccination is introduced into the UK childhood immunisation schedule.
PMCID: PMC2271686  PMID: 8760959
18.  Hepatitis B: update on perinatal management. Infectious Diseases and Immunization Committee, Canadian Paediatric Society. 
Infants of women infected with hepatitis B virus (HBV) are at risk of acquiring hepatitis B, usually at the time of delivery but occasionally in utero or after delivery. Perinatally acquired HBV infections are noteworthy for their tendency to persist throughout life, predisposing victims to cirrhosis and hepatocellular carcinoma. In most instances perinatal infection can be prevented by combined passive-active immunization of infants at risk. It is recommended that attempts be made to identify pregnant women infected with HBV and that their infants be given hepatitis B immune globulin soon after birth, then be actively immunized with HBV vaccine. This approach is effective and safe and is subsidized in many provinces.
PMCID: PMC1490952  PMID: 3955481
19.  Evidence of protection against clinical and chronic hepatitis B infection 20 years after infant vaccination in a high endemicity region 
Journal of Viral Hepatitis  2011;18(5):369-375.
Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg −/+ and HBeAg −/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0-1-2-12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti-HBs antibodies and serological markers of hepatitis B infection (anti-HBc, HBsAg, and in selected cases HBeAg, anti-HBe, HBV DNA). During the 20-year follow-up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti-HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti-HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long-term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure. ( NCT00240500 and NCT00456625)
PMCID: PMC3110864  PMID: 20384962
efficacy; hepatitis B; vaccine
20.  The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis 
Virology Journal  2012;9:185.
Chronic hepatitis B virus (HBV) infection poses a serious public health problem in many parts of the world. Presently, even with proper joint immunoprophylaxis, approximately 10-15% of newborns from HBV carrier mothers suffer from HBV infection through intrauterine transmission. One of the risk factors is the level of maternal viraemia. Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV. A few studies have evaluated the efficacy of telbivudine in preventing intrauterine HBV infection during late pregnancy. So we conducted this meta-analysis to arrive at an evidence-based conclusion. We searched Medline/PubMed, EMBASE, Cochrane Library, Web of Knowledge and China Biological Medicine Database from January 1990 to December 2011. Relative risks (RR) of the seropositivity rates for hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants were studied. Mean differences (MD) in maternal HBV DNA levels were reviewed. Finally two randomised controlled trials (RCTs) and four non-randomised controlled trials (NRCTs) were left for analysis which included 576 mothers in total, of whom 306 received telbivudine treatment and 270 did not receive any drug. All newborns received hepatitis B vaccine (HBVac) and hepatitis B immunoglobulin (HBIG) after birth. The seropositivity rate for HBsAg or HBV DNA was significantly lower in the telbivudine group, both at birth and at 6–12 months follow up. Meanwhile, maternal HBV DNA levels prior to delivery were significantly lower in the telbivudine group. In addition, the frequency of serum creatine kinase (CK) elevation was similar in the two groups. Our meta-analysis provides preliminary evidence that telbivudine application in late pregnancy is effective in the interruption of intrauterine HBV infection, with no significant adverse effects or complications. More high quality, well-designed, double-blinded, randomised controlled and large size clinical trials are needed for further investigation and more convincing results in the future.
PMCID: PMC3494585  PMID: 22947333
Hepatitis B virus; Telbivudine; Intrauterine transmission; Pregnanc
21.  A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population 
AIM: To examine the determinants of maternal-neonatal transmission of hepatitis B virus (HBV).
METHODS: A nested case-control study was conducted in Changsha, Hunan, People’s Republic of China from January 1, 2005 to September 31, 2006. To avoid potential maternal blood contamination, we collected vein blood of newborns immediately after birth and before initial hepatitis B vaccination to determine the HBV infection status of the newborn. For each HBsAg-positive infant, one HBsAg-negative infant born to an HBsAg-positive mother was matched by hospital at birth (same), gender (same), and date of birth (within 1 mo). A face-to-face interview was conducted to collect clinical and epidemiological data. Conditional logistic regression analysis was used to estimate the independent effects of various determinants on maternal-neonatal transmission of HBV.
RESULTS: A total of 141 HBsAg-positive infants and 141 individually matched HBsAg-negative infants were included in the final analysis. Maternal first-degree family history of HBV infection, intrahepatic cholestasis, and premature rupture of membranes were risk factors for perinatal transmission of HBV, whereas systematic treatment and HBV immunoglobulin injections for mothers with HBV infection were protective factors for maternal-neonatal transmission of HBV, after adjustment for potential confounding factors.
CONCLUSION: For HBsAg-positive mothers, systematic treatment, HBV immunoglobulin administration, and controlling intrahepatic cholestasis and pregnancy complications may reduce the incidence of perinatal transmission of HBV.
PMCID: PMC3180022  PMID: 21987612
HBsAg-positive; Hepatitis B virus; Perinatal transmission: Nested case-control study
22.  Hepatitis B virus infection in general population in Madagascar: evidence for different epidemiological patterns in urban and in rural areas. 
Epidemiology and Infection  1996;117(1):133-137.
To describe the features of hepatitis B virus (HBV) infection in Madagascar, a randomized sero-epidemiological survey was undertaken in the general population > or = 1 year old of two provinces which represents 45% of the total population. In the 921 sera tested, the prevalence of HBV markers was 20.5% for HBsAg, 38.2% for anti-HBc and 6.9% for HBeAg. HBsAg and anti-HBc prevalence rates were significantly higher in males. A large difference in HBsAg prevalence was observed between urban (5.3%) and rural areas (26.0%). The same contrast in prevalence was noticed for the other HBV markers. In rural areas, HBV infection was more frequently acquired early in infancy, which suggests predominantly perinatal or postnatal transmission. The presence of HBV markers was not significantly associated with a history of blood transfusion, surgery or parenteral injection. High infectivity carriers represented 5.3% and the overall frequency of chronic carriers was 10.4%. These results place Madagascar among areas of high endemicity.
PMCID: PMC2271680  PMID: 8760960
23.  Dynamic changes of HBV markers and HBV DNA load in infants born to HBsAg(+) mothers: can positivity of HBsAg or HBV DNA at birth be an indicator for HBV infection of infants? 
BMC Infectious Diseases  2013;13:524.
Neither HBV DNA nor HBsAg positivity at birth is an accurate marker for HBV infection of infants. No data is available for continuous changes of HBV markers in newborns to HBsAg(+) mothers. This prospective, multi-centers study aims at observing the dynamic changes of HBV markers and exploring an early diagnostic marker for mother-infant infection.
One hundred forty-eight HBsAg(+) mothers and their newborns were enrolled after mothers signed the informed consent forms. Those infants were received combination immunoprophylaxis (hepatitis B immunoglobulin [HBIG] and hepatitis B vaccine) at birth, and then followed up to 12 months. Venous blood of the infants (0, 1, 7, and 12 months of age) was collected to test for HBV DNA and HBV markers.
Of the 148 infants enrolled in our study, 41 and 24 infants were detected as HBsAg(+) and HBV DNA(+) at birth, respectively. Nine were diagnosed with HBV infection after 7 mo follow-up. Dynamic observation of the HBV markers showed that HBV DNA and HBsAg decreased gradually and eventually sero-converted to negativity in the non-infected infants, whereas in the infected infants, HBV DNA and HBsAg were persistently positive, or higher at the end of follow-up. At 1 mo, the infants with anti-HBs(+), despite positivity for HBsAg or HBV DNA at birth, were resolved after 12 mo follow-up, whereas all the nine infants with anti-HBs(−) were diagnosed with HBV infection. Anti-HBs(−) at 1 mo showed a higher positive likelihood ratio for HBV mother-infant infection than HBV DNA and/or HBsAg at birth.
Negativity for anti-HBs at 1 mo can be considered as a sensitive and early diagnostic indictor for HBV infection in the infants with positive HBV DNA and HBsAg at birth, especially for those infants with low levels of HBV DNA load and HBsAg titer.
PMCID: PMC3829094  PMID: 24195671
24.  Hepatitis B and hepatitis delta virus infection in South America. 
Gut  1996;38(Suppl 2):S48-S55.
About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects.
PMCID: PMC1398044  PMID: 8786054
25.  High Endemicity and Low Molecular Diversity of Hepatitis B Virus Infections in Pregnant Women in a Rural District of North Cameroon 
PLoS ONE  2013;8(11):e80346.
A program, supported by the GEMHEP (Groupe d'étude Moléculaire des Hépatites), was established in 2007 in the sanitary district of Tokombéré, to prevent perinatal transmission of hepatitis B virus (HBV). It comprises screening for HBV surface antigen (HBsAg) in all pregnant women and vaccinating the newborn if tests are positive.
Methods/Principal Findings
1276 women were enrolled in the study after providing informed consent. Demographic data and blood samples were available for 1267 of the enrolled patients. HBsAg was determined locally using a rapid test (Vikia HBsAg, Biomerieux). Tests for HBV and HDV virological markers (HBeAg, anti-HDV antibodies (Ab), HBV-DNA, HDV-RNA, HBV and HDV genotypes) were performed on the confirmed HBsAg-positive samples in the virology unit of the Angers University Hospital (France). HBsAg was found in 259 of the 1267 pregnant women (20.4%) between January 2009 and April 2010, of whom 59 were HBeAg-positive (22.7%) with high levels of HBV-DNA. Anti-HDV Ab were found in 19 (7.3%) of the HBsAg-positive women. The prevalence rates of HBsAg and HDV were not age-dependent whereas HBeAg carriers were statistically younger than non carriers. Basal core promoter (BCP) and precore (PC) mutations and genotypes were determined by sequencing. Of 120 amplified sequences, 119 belonged to HBV genotype E (HBV/E) and the 9 HDV strains belonged to HDV clade 1. In the PC region, 83/228 patients (36.4%) harbored a G1896A mutant or mixed phenotype virus. In the BCP region, the double mutation A1762T/G1764A and the G1757A substitution were detected respectively in 26/228 patients (11.4%) and 189/228 patients (82.8%).
Our results confirm the high prevalence and low molecular diversity of HBV in Far Northern Cameroon; more than 20% of the infected women were highly viremic, suggesting a high rate of HBV perinatal transmission and supporting the WHO recommendation to vaccinate at birth against hepatitis B.
PMCID: PMC3827216  PMID: 24265811

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