Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission.

OBJECTIVE: To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission. METHODS: We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay. RESULTS: There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission. CONCLUSION: PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.

Placental expression of asialoglycoprotein receptor associated with Hepatitis B virus transmission from mother to child.

BACKGROUND: Asialoglycoprotein receptor expression on hepatocytes has been associated with endocytosis, binding and uptake of hepatitis B virus. The role of asialoglycoprotein receptor in hepatitis B virus vertical transmission and its expression on placenta has not yet been studied. PATIENTS AND METHODS: Thirty-four HBsAg+ve and 13 healthy pregnant mothers along with their newborns were enrolled. The former were categorized into transmitting and non-transmitting mothers based on their newborns being hepatitis B surface antigen and hepatitis B virus DNA positive. Expression of asialoglycoprotein receptor and hepatitis B surface antigen in placenta and isoform of asialoglycoprotein receptor on dendritic cell in peripheral and cord blood dendritic cells were analysed using flowcytometry, immune histochemistry, immune florescence and qRT-PCR. RESULTS: Twelve HBsAg+ve mothers transmitted hepatitis B virus to their newborns whereas the rest (n = 22) did not. Hepatitis B virus-transmitting mothers showed increased expression of asialoglycoprotein receptor in trophoblasts of placenta. Immunofluorescence microscopy revealed colocalization of hepatitis B surface antigen and asialoglycoprotein receptor in placenta as well as in DCs of transmitting mothers. There was no significant difference in the expression of asialoglycoprotein receptor on peripheral blood mononuclear cells or chord blood mononuclear cells between the 2 groups. However, hepatitis B virus-transmitting mothers and their HBsAg+ve newborns showed increased mRNA levels of isoform of asialoglycoprotein receptor on dendritic cell in peripheral blood mononuclear cells. Hepatitis B virus-transmitting mothers and their HBsAg+ve newborns showed an increased expression of isoform of asialoglycoprotein receptor on dendritic cell on circulating dendritic cells compared to hepatitis B virus non-transmitting mothers and their negative newborns. CONCLUSIONS: This study revealed that increased expression of asialoglycoprotein receptor in placenta and colocalization with hepatitis B surface antigen strongly indicates its role in intrauterine transmission of hepatitis B virus. Asialoglycoprotein receptor-blocking strategy can be used for therapeutic intervention of vertical transmission.

Prevention strategy for father-to-child transmission of hepatitis B virus: a systematic review and meta-analysis.

OBJECTIVE: Father-to-child transmission (FTCT) occurs in infants born to hepatitis B virus (HBV) infected father. In this study, we aim to summarize the prevention strategy for FTCT of HBV by systematic review and meta-analysis. METHODS: PubMed and China Knowledge Resource Integrated Database were systematically searched. We systematically reviewed the prevention strategy for father, mother, and infant before, during pregnancy and after birth. We also examined trial sequential analysis (TSA) for the required information size (RIS). RESULTS: Fourteen studies with 2825 father-mother-child pairs included in the studies. Two publications assessed father antiretroviral therapy before pregnancy, with the mean FTCT incidence 3.5% in the antiretroviral therapy group and 12.0% in the control group. The summary OR compared between two groups was 0.280 (95% CI 157-0.500; Z = 4.30, p < .00001) by random-effects model. TSA showed further studies were needed. Twelve publications assessed maternal immunoprophylaxis before and during pregnancy, with the mean FTCT incidence 14.9% in the maternal immunoprophylaxis group and 32.8% in the control group. The summary OR compared between two groups was 0.343 (95% CI 252-0.468; Z = 6.77, p < .00001) by random-effects model. TSA showed no further studies were needed. No randomized controlled trials (RCT) and non-RCTs were found assessing neonate and infant immunoprophylaxis for FTCT prevention. CONCLUSION: Father antiretroviral therapy before pregnancy, maternal immunoprophylaxis before and during pregnancy, and neonate and infant immunoprophylaxis are important prevention strategy for FTCT of HBV. However, this conclusion should be confirmed by high quality randomized controlled trials.

Secukinumab for psoriasis in a patient with hepatitis B.

The case reported describes a 48-year-old man with congenital hepatitis B receiving secukinumab for treatment of psoriasis. Some biologic therapies have been associated with an increased risk of reactivation of hepatitis B. In the case of this patient, secukinumab has successfully managed his psoriasis without evidence of hepatitis B virus reactivation.

[Early physical growth and disease analysis among children born delivered by HBsAg-positive mothers].

Objective: To estimate the early physical growth and disease in children born to HBsAg-positive mothers. Methods: This was a retrospective cohort study. Three areas as Xihu in Hangzhou, Lanxi in Jinhua, and Haiyan in Jiaxing in Zhejiang province were selected by cluster sampling. The growth outcomes of children born to HBsAg-positive mothers (exposure group) and matched 1∶1 women uninfected with HBV (control group) in 2014 were investigated and compared at birth, 6, 9, 12, and 18 months, respectively. There were totally 342 children in each group. Results: The incidences of low birth weight (LBW) for children born to exposure and control group were 1.8% (6/342), and 2.6% (9/342), respectively (P=0.433); and, rates of preterm birth were 2.3% (8/342), and 2.0% (7/342), respectively (P=0.794). The mean birth weight of children born to mothers without HBV infection (3.4±0.4) kg was dramatically higher than children in exposure group (3.3±0.4) kg (P=0.019). At 18 months, the average head circumference was significantly greater among children in control group (47.3±1.3) cm than children in exposure group (47.0±2.0) cm (P=0.038). Additional, mean birth weeks, height, weight, increases in height/weight/head circumference each month, weight/height/head circumference for age Z scores, proportion of growth retardation and low weight, disease prevalence were not observed statistically differences between two groups (P>0.05). All children born to HBsAg-positive mothers were received three-dose HBV vaccination. The rate of hepatitis B immunoglobulin for births born to HBsAg-positive was 98.8% (338/342). Mother to children transmission of HBV at 18 months was 1.0% (1/97). Conclusion: No significant differences in growth development and disease prevalence were found among children born to HBsAg-positive women and women without HBV infection.

Hepatitis B Immunoprophylactic Failure and Characteristics of the Hepatitis B Virus Gene in Mother-Infant Pairs in Parts of China.

OBJECTIVE: To determine the hepatitis B immunoprophylactic failure rate in infants born to hepatitis B virus (HBV) infected mothers and to characterize HBV genes. METHODS: HBV-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. RESULTS: The 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. CONCLUSION: The 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.

Estudo transversal do perfil das infecções congênitas atendidas entre 2012 e 2014 em um centro de referência em Belo Horizonte, Minas Gerais / Cross-sectional study of clinical and laboratorial aspects of congenital infections attended at a reference Center in Belo Horizonte, MG, 2012-2014

Introdução: as infecções congênitas são resultantes da transmissão vertical de microrganismos de gestantes infectadas para seus conceptos. Apesar dessas infecções, em geral, cursarem com pouca ou nenhuma manifestação clínica nas gestantes, a infecção fetal pode trazer morbimortalidade perinatal e na infância. Objetivo: identificar a prevalência das infecções congênitas encaminhadas ao Centro de Referência e Treinamento em Doenças Infecciosas e Parasitárias Orestes Diniz (CTR/DIP Orestes Diniz) e avaliar os métodos laboratoriais usados para o diagnóstico. Métodos: estudo transversal realizado em ambulatório de referência em doenças infecciosas, a partir de coleta de dados de prontuários de crianças com diagnóstico suspeito de infecção congênita. A confirmação diagnóstica baseou-se em testes sorológicos ou de biologia molecular, além de descrição de sintomatologia da criança. Resultados: um total de 513 crianças foram identificadas, sendo que 41,3% tiveram o diagnóstico confirmado, a maioria foi de toxoplasmose (45,35%) e sífilis (15,98%). Entre as crianças com diagnóstico confirmado, 28,85% apresentaram manifestações clínicas, enquanto que no grupo com diagnóstico indeterminado ou suspeito o percentual foi de 16,38%. As principais manifestações identificadas foram acometimento do sistema nervoso central (n=39) e alterações visuais (n=30). Conclusão: a confirmação de infecção foi definida em aproximadamente metade dos pacientes avaliados e a maioria das crianças foi assintomática ao nascimento. O pré-natal de qualidade e a propedêutica e tratamento precoce das crianças identificadas podem reduzir o impacto dessas infecções no nosso meio.(AU)

Introduction: congenital infections are results of microorganisms transmitted to the fetus by the infected pregnant. Most newborn infants infected during pregnancy or labor have no sings of congenital disease. However, these infections may cause perinatal and infancy morbidity and mortality. Objective: to determine the prevalence of congenital infections in newborns and infants attended at the CTR/DIP Orestes Diniz (Centro de Treinamento e Referência em Doenças Infecciosas e Parasitárias Orestes Diniz) and to analyse the laboratorial methods used for diagnosis of congenital disease of assisted children. Methods: cross-sectional study conducted in an Infectious Diseases Reference Center where it was evaluated the charts of infants with suspected congenital infection. Diagnosis confirmation was based on serological tests, molecular biology and signs and symptoms described in the charts. Results: A total of 41,3% of the 513 children identified have had a defined diagnosis. Most of them had toxoplasmosis (45,35%) and syphilis (15,98%). Clinical manifestations was observed in 28,85% of children with defined diagnosis of congenital infection, and in 16,38% of children with uncertain diagnosis. Central Nervous System (n=39) and ocular (n=30) manifestations were the most frequent findings. Conclusions: Defined diagnosis was possible in about half of cases and most of them were asymptomatic at birth. An appropriate prenatal care and early diagnosis and treatment of congenital infections may reduce the impact of disease in the population.(AU)

Study of the relationship in pregnant women between hepatitis B markers and a placenta positive for hepatitis B surface antigen.

AIMS: A placenta with hepatitis B virus (HBV) is one of the main reasons for transplacental transmission during pregnancy. This study aims to explore the factors influencing the presence of hepatitis B surface antigen (HBsAg) in the placenta and the synergistic effect of these factors. METHODS: A total of 155 placentae and blood specimens were collected from HBsAg-positive mothers and their newborns. HBsAg in placenta was detected using the immunohistochemistry method. HBV serum markers were detected using enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods. RESULTS: The results showed that hepatitis B e antigen (HBeAg) positive, or HBV DNA positive status, is significantly associated with an HBsAg-positive placenta. A synergistic effect was present. The hazard ratio for a HBsAg-positive placenta in mothers with HBeAg and HBV DNA was 1.97 times higher than the sum of the independent relative risk of each separate effect (synergy index, S=1.97). There was a statistically significant association between HBsAg in newborns and HBsAg in placenta, and the risk of newborns with HBsAg was greater (odds ratio values 3.33 and 5.31, respectively) when placental cells close to the fetal side were HBsAg positive. CONCLUSIONS: Being positive for HBeAg and/or HBV DNA are significant risk factors for HBsAg in the placenta. HBsAg can pass through the placenta via cellular transfer, possibly contributing to transplacental transmission.

Risk factors for intrauterine infection with hepatitis B virus.

OBJECTIVE: To investigate risk factors for hepatitis B virus (HBV) intrauterine infection. METHODS: Peripheral blood samples and clinical data were collected from 174 pregnant women who were positive for hepatitis B surface antigen (HBsAg). Their 176 neonates received an active-passive immunization schedule at 0, 1, and 6 months. Blood samples from the infants, collected before immune prophylaxis administration, were tested for HBV markers and HBV DNA. RESULTS: The intrauterine infection rate at 6 months after birth was 5.1%. Maternal HBV DNA positivity (OR 11.362; 95% CI, 1.389-92.931), hepatitis B e antigen (HBeAg) positivity (OR 7.278; 95% CI, 1.734-30.538), and thalassemia minor (OR 15.619; 95% CI, 2.239-108.964) were associated with intrauterine infection. The intrauterine infection rate for mothers with 10(5) copies/mL of serum HBV DNA or more was 18.2%, compared with 0.8% for mothers with less than 10(5) copies/mL. CONCLUSION: A positive HBsAg test at 24 hours and/or 1 month of age followed by a positive test at 6 months is an objective and comprehensive criterion for the diagnosis of HBV intrauterine infection. Maternal HBV DNA positivity (especially 10(5) copies/mL of HBV DNA or more), HBeAg positivity, and thalassemia minor are risk factors for HBV intrauterine infection.

Which newborns missed the hepatitis B birth dose vaccination among U.S. children?

OBJECTIVES: Hepatitis B birth dose vaccination is a critical step in preventing perinatal hepatitis B virus infection. This study assesses the prevalence of children who missed the birth dose of hepatitis B vaccination and identifies socio-demographic factors associated with non-receipt of the birth dose among children in the United States. METHODS: A survey observation study was conducted with the national representative sample of 17,053 U.S. children aged 19-35 months obtained from the 2009 National Immunization Survey. Categorical data analysis and multivariable logistic regression in the context of complex sample survey were applied to evaluate the prevalence and determine the independent risk factors. RESULTS: 39.2% of children missed the birth dose of hepatitis B vaccination. Children who reside in states without a universal hepatitis B vaccine supply policy, are not covered by health insurance, and have only 1 vaccination provider are significantly associated with non-receipt of the birth dose hepatitis B vaccination. CONCLUSIONS: Children who reside in states without a universal hepatitis B vaccine supply policy, and who are not covered by health insurance are two important modifiable risk factors for not receiving the birth dose hepatitis B vaccination. Future intervention studies could be needed to help control those modifiable risk factors.

Development of strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers.

This study aimed at developing strategies for screening, predicting, and diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers. A total of 1,360 infants born to 1,355 HBsAg positive mothers were followed for 1 year. All newborn infants received active and passive immunization within 24 hr after birth. Maternal and infant blood samples were collected and tested for the status of serum HBsAg, HBeAg, and HBV DNA positivity. The accuracy of infant HBsAg positivity, HBV DNA positivity, HBsAg and HBV DNA double positivity, and HBsAg and/or HBV DNA positivity at birth in the diagnosis of intrauterine HBV infection was evaluated by receiver operating characteristic curve analysis. Of 1,360 infants, 145 tested positive for HBsAg and/or HBV DNA at birth. Twenty-one (1.5%) infants, who were diagnosed with intrauterine HBV infection, showed HBsAg positivity from birth to 7 and 12 months of age. Infant HBsAg positivity at birth had the highest sensitivity in predicting intrauterine HBV infection, while neonatal HBsAg and HBV DNA double positivity had the highest specificity. These findings suggest that infants, who were born to HBsAg positive mothers and were positive for both HBsAg and HBV DNA at birth, may be at a higher risk for intrauterine HBV infection. HBsAg positivity at birth may be a good marker for screening intrauterine HBV infection. Infant HBsAg positivity both at birth and 7 months of age may be used as a diagnostic criterion to simplify diagnostic procedures and improve diagnostic efficiency.

Low levels of knowledge and preventive practices regarding vertical hepatitis B transmission among perinatal nurses.

OBJECTIVE: To evaluate current levels of hepatitis-B-related knowledge and clinical practice among perinatal nurses. DESIGN: Cross-sectional study. SETTING: Santa Clara County, California, home to one of the largest U.S. populations at risk of perinatal hepatitis B transmission. PARTICIPANTS: Perinatal nurses (N = 518) from eight birthing hospitals. METHODS: In 2008-2010, nurses completed a baseline survey evaluating existing hepatitis-B-related knowledge and preventive clinical practices, participated in an educational seminar, received instructional materials about hepatitis B, and completed a follow-up knowledge survey. RESULTS: Eighty percent of perinatal nurses had provided health care to a pregnant woman with chronic hepatitis B, but only 51% routinely provided patients with educational information about hepatitis B. While 75% routinely informed patients about effective methods to prevent mother-to-child transmission, only a small minority (17-34%) educated infected women about standard recommendations for protecting themselves and household members. One fourth or fewer nurses correctly answered most questions about hepatitis B prevalence, risks, and symptoms. After the educational seminar, knowledge increased statistically significantly. CONCLUSION: Existing knowledge about hepatitis B is limited, and nationally recommended preventive clinical practices are commonly overlooked by perinatal nurses. This lack of knowledge and preventive care represents a noteworthy gap and an opportunity for targeted training and education to improve perinatal hepatitis B prevention and medical management of infected mothers.

Homoharringtonine as a backbone drug for the treatment of newly diagnosed pediatric acute myeloid leukemia: a report from a single institution in China.

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in the treatment of acute myeloid leukemia (AML). The purpose of this study was to evaluate the efficacy and toxicity of HHT for de novo pediatric AML. Patients entered in this study were treated with a regimen including HHT 3.5 mg/m(2) day for 9 days for 6-8 cycles after induction and consolidation with cytarabine plus daunorubicin (DA). One hundred and seventy-one eligible patients, with a median age of 7.58 years, were enrolled. Complete response was obtained in 140/171 (81.9%) cases within 60 days (2 cycles) after DA induction. The 5-year event-free survival was 52.75%. Severe myelosuppression was seen in all patients, with an average minimum WBC count of 686/µl. Following the HHT-including regimen, one patient suffered severe pancreatitis, and a second with a history of congenital hepatitis B suffered liver failure. No significant drug-induced hypotension, fluid retention, hyperglycemia, or cardiac toxicity was detected in this study. Other toxicities, including nausea, vomiting, diarrhea, and mucositis, were mild. HHT-including protocols may emerge as useful therapeutic options in future clinical trials.

HBV viremia in newborns of HBsAg(+) predominantly Caucasian HBeAg(-) mothers.

BACKGROUND: Hepatitis B virus infection is an important public health problem worldwide and eliminating mother-to-infant transmission is important to decrease the prevalence of chronic HBV-infection. Although, immunoprophylaxis given at birth largely prevents mother-to-infant transmission, perinatal HBV viremia has been reported in HBsAg(-) newborns born mainly to HBeAg(+) women in endemic areas. OBJECTIVES: To examine the incidence of perinatal HBV viremia in newborns of HBsAg(+) predominantly HBeAg(-) mothers. STUDY DESIGN: Peripheral blood was obtained at birth from 109 HBsAg(+) mothers and their newborns before the administration of active-passive immunoprophylaxis. Infants were prospectively followed and appropriately vaccinated. RESULTS: Although most (92.7%) of the HBsAg(+) mothers were HBeAg(-), 73.4% had detectable HBV viremia. Neonatal viremia was detected in 3/8 (37.5%) and 24/101 (23.8%) newborns of HBeAg(+) and HBeAg(-) mothers, respectively (p=0.386). However, HBV-DNA levels were significantly higher in newborns of HBeAg(+) mothers (p=0.025). No child developed chronic HBV infection, but one child had evidence of subclinical hepatitis. CONCLUSIONS: Although the clinical significance of low viremia levels in almost one in four newborns of HBsAg(+) mothers in a low endemicity area is unclear, it may enhance our understanding of HBV mother-to-infant transmission.

Seroprevalence of HIV, hepatitis B, and syphilis among pregnant women at the general hospital, Guatemala City, 2005-2009.

BACKGROUND: sexually transmitted infection (STI) screening in pregnancy provides an excellent opportunity for secondary prevention. OBJECTIVE: to document the epidemiology of HIV, hepatitis B, and syphilis among pregnant women at a Guatemalan national hospital. RESULTS: from 2004 to 2009, 118 (0.76%) of 15 563 of women tested in the prenatal clinic had HIV infection, 29 (0.22%) of 13 028 women tested had hepatitis B virus infection, and 78 (0.60%) of 13 027 had a positive test for syphilis. From August 1, 2007 through December 31, 2009, 29 482 women were tested in the obstetrical emergency room. A total of 63 were HIV positive (0.21%), 48 had hepatitis B (0.16%), and 196 had syphilis (0.66%). Of the 9196 births between August 2007 and July of 2008, 33 (0.36%) were to HIV-infected mothers. CONCLUSION: these 3 STIs were uncommon in our population and did not increase in incidence during the study period. HIV maternal-to-child transmission (MTCT) prevention programs were feasible in our setting.

Management of chronic hepatitis B in pregnancy.

Providing appropriate treatment and follow-up to hepatitis B virus (HBV)-infected mothers and their newborns is critical in preventing HBV mother-to-child transmission (MTCT) and eradicating HBV infection. Although highly effective in preventing MTCT, standard passive-active immunoprophylaxis with hepatitis B immunoglobulin and the hepatitis B vaccine may have a failure rate as high as 10% to 15%. Antiviral treatment has been used during pregnancy and may decrease MTCT. Several issues must be addressed in future clinical studies before universal recommendations for antiviral therapy for pregnant women can be made.

Hepatitis B vaccination: disease and cancer prevention-a Taiwanese experience.

Prevention is most cost effective toward successful control of hepatitis B virus (HBV) infection and its complications. It is particularly urgent where HBV infection and hepatocellular carcinoma (HCC) are prevalent. To achieve better results of primary HCC prevention globally, higher world coverage rates of HBV vaccine, better strategies against breakthrough infection/nonresponder, and good long-term protection are needed. With the universal hepatitis B vaccination program starting from neonates in most countries, HBV infection and its complications will be further reduced in this century. An effective decline in the incidence of HCC in adults is expected in the near future. The concept of a cancer preventive vaccine, using HBV as an example, can be applied further to other infectious agents and their related cancers.