Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

OBJECTIVETo evaluate the long-term protection efficacy of neonatal hepatitis B vaccination on chronic hepatitis B (CHB) and liver fibrosis and cirrhosis in adults.

METHODSFrom January to October, 2013, a cross-sectional study was conducted among the participants from Qidong Hepatitis B Intervention Study (QHBIS), who were selected through stratified random sampling. The detections of serum alanine aminotransferase (ALT), HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe were conducted and ultrasonography on liver, gallbladder and spleen was performed for them. The positive rates of each serologic markers, the prevalence of active CHB and liver fibrosis and cirrhosis were calculated, the gender specific differences between vaccination group and control group were compared with Chi-square test.

RESULTSA total of 4 421 participants aged (25.59±1.84) years in vaccination group and 3 880 participants aged (26.61±2.24) years in control group were surveyed. The positive rates of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 2.38%, 37.73%, 3.78%, 0.57% and 2.15% in vaccination group, and 9.02%, 29.41%, 16.83%, 2.73% and 8.87% in control group, respectively, the differences between two groups were statistically significant (all P<0.05). The prevalence of active CHB and liver fibrosis and cirrhosis were 0.45% and 0.16% in vaccination group, 1.29% and 0.39% in control group, the differences between two groups were statistically significant (P<0.05). The active CHB prevalence was lower in females than in males in both vaccination group and control group (P<0.05). The liver fibrosis and cirrhosis prevalence was lower in females than in males in control group (P<0.05); whereas, no statistical significant difference in liver fibrosis & cirrhosis prevalence between males and females was found in vaccination group (P>0.05).

CONCLUSIONSProtection conferred by neonatal hepatitis B vaccination could last to marrying age. The gender specific difference in protection efficacy needs further study.

Adult ; China ; Cross-Sectional Studies ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Hepatitis B, Chronic ; prevention & control ; Humans ; Liver Cirrhosis ; Male ; Prevalence ; Vaccination ; statistics & numerical data

Occult hepatitis B virus infection (OBI) could occur in infants born to HBsAg-positive mothers after active and passive immunization, even though their serological patterns suggested successful protection from HBV mother-to-infant transmission according to the current criteria of being HBsAg-negative and anti-HBs positive. We should take into account its potential clinical impact and reconsider the effectiveness of the present immunoprophylaxis against HBV in this population. This review will focus on topics including the prevalence, serological features and probable risk factors underlying the phenomenon of OBI in infants with HBsAg carrier mothers after immunization.
Carrier State ; Child ; Female ; Hepatitis B ; prevention & control ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Humans ; Immunization ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Prevalence ; Risk Factors

The recent outbreak of hepatitis C virus (HCV) at Singapore General Hospital (SGH) has highlighted the dangers of viral hepatitis. In this case, infection control and environmental contamination were the culprits, particularly, a drop of blood containing 5 million IU HCV. From a broader perspective, there has been a revolution in HCV therapy with the recent rapid evolution of short-term (12 weeks) safe, all oral directly- acting antiviral (DAA) therapy leading to cure rates of 90% to 100%, even in previously difficult to treat patients with liver cirrhosis, previous treatment failure and those on immunosuppression. Consequently, treating HCV in risk groups such as renal dialysis and haemophiliacs can eliminate a pool of infected patients to prevent future outbreaks. A seroprevalence study is needed to identify a possible "birth cohort" effect that could aid screening. For HBV, vaccination has reduced prevalence to 3.8%, but these patients are prone to complications such as HBV flares. Since 2014, 13 patients developed liver failure and were listed for liver transplantation at National University Hospital (NUH) but 6 died beforehand. This avoidable catastrophe is due to undiagnosed HBV infection or patients who did not return for follow-up. Good antiviral therapy is available, but the issues are similar to HCV, identification of patients and linkage to care. A cure seems likely in the future as pharmaceutical companies are developing new agents. Singapore has joined in this initiative with a recent award of a national research translational grant to better understand the pathophysiology and the processes needed for a cure of HBV.
Antiviral Agents ; therapeutic use ; Disease Outbreaks ; prevention & control ; Health Services Accessibility ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; epidemiology ; prevention & control ; Hepatitis C, Chronic ; drug therapy ; epidemiology ; Humans ; Patient Selection ; Risk Assessment ; Singapore ; epidemiology

OBJECTIVETo determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes.

METHODSHBV-serological testing was conducted for pregnant women and infants. The complete genomes of 30 HBV isolates were sequenced, and genetic characteristics were analyzed using MEGA 5 software.

RESULTSThe immunoprophylactic failure rate for infants who had completed the scheduled hepatitis B vaccination program was 5.76% (32/556). High sequence homology (99.8%-100%) was observed in 8 of the 10 mother-infant pairs. We identified 19 subgenotype C2 strains, 9 subgenotype B2 strains, and 2 subgenotype C1 strains. Three serotypes were detected: adr (19/30), adw (9/30), and ayw (2/30). The frequency of amino acid mutation of the 'a' determinant region was 16.67% (5/30), including that of Q129H, F134Y, S136Y, and G145E. We detected 67 amino acid mutations in the basal core promoter, precore, and core regions of the genome.

CONCLUSIONThe immunoprophylactic failure rate in infants born to HBV-infected mothers is low in the regions of China examined during this study. Moreover, HBV mutation in the 'a' determinant region could not account for immunoprophylactic failure for all infants.

Adult ; Animals ; CHO Cells ; China ; epidemiology ; Cricetinae ; Cricetulus ; Female ; Hepatitis B ; congenital ; epidemiology ; prevention & control ; transmission ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; genetics ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Mutation ; Phylogeny ; Pregnancy ; Treatment Failure ; Young Adult

Mother-to-child transmission (MTCT) is the main way to transmit hepatitis B virus (HBV), and it is also the biggest contributor to high prevalence of hepatitis B in high endemic areas. Therefore, preventing MTCT may result in the decline of HBV positive ratio foundationally. Hepatitis B vaccination is currently recognized as the most economic, effective and safe measure to prevent MTCT. The key strategies in the future to prevent MTCT should be to enhance the screening of hepatitis B surface antigen, to provide the infants born to surface antigen positive mother with hepatitis B vaccine combine with hepatitis B immunoglobulin(HBIG), and to monitor the effect of the intervention.
Female ; Hepatitis B ; prevention & control ; transmission ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Humans ; Immunoglobulins ; therapeutic use ; Infant ; Infectious Disease Transmission, Vertical ; prevention & control ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Prevalence ; Vaccination

Child ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Vaccines ; administration & dosage ; therapeutic use ; Humans ; Patient Acceptance of Health Care ; Vaccination

OBJECTIVETo explore the factors influencing failure of an immunization to interrupt perinatal (mother-to-child) transmission of hepatitis B virus (HBV).

METHODSBetween June 2006 and March 2010, a total of 1355 pregnant women testing positive for the hepatitis B surface antigen (HBsAg), at gestational weeks 20 to 42, and without use of antiviral or immunomodulatory drugs during the pregnancy were prospectively recruited to the study. The mothers were given a choice of receiving hepatitis B immunoglobulin (HBIG; three 200 IU intramuscular injections give at four-week intervals starting from gestation week 28) or not. All neonates (1360, including five sets of twins) received hepatitis B vaccine (10 mug) plus HBIG (200 IU) combined immunization within 24 h of birth, as early as possible. Peripheral venous blood samples were collected from the neonates within 24 h of birth and at 7 and 12 months of age for detection of HBV markers, including hepatitis B e antigen (HBeAg) and HBV DNA. The infants were classified according to HBV perinatal transmission status (infection group and non-infection group) and various factors (maternal-related: age, gravidity, parity; pregnancy/birth-related: threatened premature labor, complications; neonate-related: sex, birth weight, apgar score) were compared between the two groups by using non-conditional logistic regression analysis to determine their potential influence on failure of immunization to inhibit transmission.

RESULTSAfter 12 months of follow-up, 1.54% (21/1360) of the neonates had presented with HBV infection. Analysis of the HBV-infected neonates revealed differences in infection rates between neonates born to mothers with HBIG injection (2.22% vs. without HBIG injection: 1.11%, P less than 0.05) and caesarean section (1.35% vs. vaginal delivery: 1.73%) but neither reached statistical significance (P less than 0.05); only the practice of breastfeeding showed a significant difference for infection rate, with neonates fed artificial formula having higher infection rate (3.13%) than the breastfed neonates (0.27%, P less than 0.05). The neonate HBV infection rate was also significantly higher for neonates born to HBeAg-positive mothers (4.44% vs. HBeAg-negative mothers: 0%, P less than 0.05) and HBV DNA-positive mothers (3.13% vs. HBV DNA-negative mothers: 0%, P less than 0.05). When the mothers were stratified by serum level of HBV DNA, there was a significant difference in HBV-infected neonates born to mothers with more than or equal to 1*10(7) IU/ml(6.01% vs. 10(3)-10(6) IU/ml: 0.56% and less than 1*10(3) IU/ml: 0%, both P less than 0.05). Logistic regression analysis indicated that the independent risk factors for HBV perinatal transmission despite immunization were maternal serum HBeAg-positive status (relative risk (RR)=31.74, 95% confidence interval (CI): 3.88-259.38) and maternal HBV DNA of ≥ 10⁷ copies/mL (RR=22.58, 95% CI: 4.75-107.40).

CONCLUSIONFailure of vaccine plus HBIG to interrupt mother-to-child transmission of HBV is influenced by maternal serum HBeAg-positive status and maternal HBV DNA of ≥10⁷ copies/mL.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B ; prevention & control ; transmission ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Humans ; Immunoglobulins ; therapeutic use ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; prevention & control ; virology ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Prospective Studies ; Risk Factors ; Viral Load

OBJECTIVETo conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group.

METHODSTwo-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers.

RESULTSThe overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to 15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at 12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001).

CONCLUSIONCombined immunoprophylaxis is therapeutically efficacious for treating infants born to HBsAg positive mothers. Monitoring these infants' anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.

Female ; Hepatitis B ; blood ; immunology ; prevention & control ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B Vaccines ; therapeutic use ; Humans ; Infant ; Mothers ; Prospective Studies ; Viral Load

BACKGROUND/AIMS: Hepatitis B virus (HBV) is the major cause of chronic liver disease in Korea, but viral prevalence has decreased because of hepatitis B vaccination programs. In this study, we investigated longitudinal changes in HBV in fection in the general Korean population. METHODS: HBV surface antigen (hepatitis B surface antigen, HBsAg) seropositivity was assessed from the Korea National Health and Nutrition Examination Survey (I to V). In total, 50,140 subjects were tested for serum HBsAg positivity over a period of 12 years (1998 to 2010). RESULTS: The prevalence of HBsAg seropositivity decreased over the study period. The rates of HBsAg carriers were 4.61% in 1998, 4.60% in 2001, 3.69% in 2005, 3.01% in 2008, and 2.98% in 2010 (p < 0.0001). The reduction in HBV infection rates was more prominent in younger age groups. Among teenagers (10 to 19 years), the percentage of HBsAg carriers decreased from 2.2% in 1998 to 0.12% in 2010 (p < 0.0001). Among those aged 10 to 39 years, the percentage of HBV infection decreased from 4.72% in 1998 to 2.29% in 2010 (p < 0.0001). However, no decreasing trend in HBsAg positivity was observed among those aged 50 or older (p > 0.05). Neither gender nor socioeconomic status were associated with the decreased prevalence of HBsAg carriers. CONCLUSIONS: HBV infection has decreased in the Korean population since the advent of vaccination programs. However, the decrease is limited to the younger population, and viral persistence remains in the middle-aged and older population.
Adolescent ; Adult ; Age Distribution ; Age Factors ; Aged ; Biological Markers/blood ; Chi-Square Distribution ; Child ; Cross-Sectional Studies ; Female ; Health Surveys ; Hepatitis B/diagnosis/*epidemiology/prevention & control ; Hepatitis B Surface Antigens/blood ; Hepatitis B Vaccines/therapeutic use ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Seroepidemiologic Studies ; Socioeconomic Factors ; Time Factors ; Young Adult