Relationship between the different replication status of HBV and mutations in the core promoter in mothers and their children infected via mother-to-infant transmission

OBJECTIVE: To study the relationship between the different replication status of hepatitis B virus (HBV) and mutations in the core promoter (CP) in mother and her child infected by mother-to-infant transmission. METHODS: The core promoter was amplified by PCR and cloned into pGEM-T vector with the T-A choning technique. The recombinant plasmid pGEM-CP was confirmed by digestion with restriction enzyme Apa I and Sac I. Two clones were selected to be sequenced in each patient. RESULTS: Every pair of mother and child had same serotype and genotype and the homology of nucleotides encoding 'a' determinant was 98%-100%. The number of mutations in the core promoter of patients with a high replication status was less than that in those with a low replication status. Mutations were mainly distributed in basia core promoter (BCP) and the inbibitor region of Kunitz-type serine protease. This difference was not associated with mother or child. CONCLUSION: The different replication status of HBV is caused by mutations in the core promoter in mother and child infected hy mother-to-infant transmission and appears to be not associated with the status of development of the infection.

Risk factors affecting the mother-to-infant transmission of hepatitis B virus: a meta analysis

Objective：To search for risk factors that affect mother-to-infant transmission of hepatitis B virus（HBV）. Methods：To obtain studies eligible for meta-analysis, China biological medicine discs and MEDLINE citations were surveyed. Mother HBV DNA or HBeAg positivity,neonate HBeAg positivity, mode of delivery, threatened abortion and threatened premature labor were processed with meta analysis. Criteria for selection of published studies for meta analysis were based on principle by Abdolmaleky HM. Odds ratio （OR） was calculated and summarized by fixed effect model or random-effects model using RevMan software. The heterogeneity of the group of ORs was assessed using an X^2 test. The significance of the pooled OR was determined by the u-test. The strength of association was assessed using the OR. An OR〉1. 0 indicated a positive association between the risk factor and neonate HBV infection. Results： After meta analysis of factors concerned, a significant association was found between the positivity of HBeAg in mother and neonate, of HBV DNA in mother peripheral serum, and HBV mother-to-infant transmission, with a pooled OR equal to 19.43 （95% CI=8. 77-43. 06）, 36.5 （95% CI= 19.85-67. 11）, and 36.5 （95 % CI= 19.85-67.11 ） respectively. Mode of delivery, threatened abortion and threatened premature labor proved not to be of risk factors on the mother-to-infant transmission of HBV. Conclusion： Mother HBV DNA or HBeAg positivity and neonate HBeAg positivity were proved to be of risk factors affecting the transmission of HBV from mother to fetal.

Issues Meriting Further Study in Preventing Mother-to-Infant Transmission of Hepatitis B by Antiviral Therapy During Pregnancy

Mother-to-infant transmission of hepatitis B virus(HBV)is a main cause of chronic HBV infection.Maternal high HBV DNA level or positive hepatitis B e antigen(HBeAg)is the major risk factor for the transmission.With recommended passive and active immunoprophylaxis,the transmission occurs in nearly 0 and 4-12%of infants born to HBV-infected mothers with negative and positive HBeAg,respectively.Therefore,pregnant women with negative HBeAg appear not requiring antiviral therapy to prevent mother-to-infant transmission of HBV.Recent studies demonstrated that oral antivirals(lamivudine,telbivudine,or tenofovir)in pregnant women with high viral load or positive HBeAg,starting from 28-32 weeks of gestation,together with neonatal immunoprophylaxis,can almost completely prevent the transmission,indicating that it does not require antiviral therapy before 28 weeks of gestation.Accumulated evidence showed that the antivirals may be stopped upon delivery,and the infants may receive breast feeding after birth.However,these issues,as well as HBV DNA threshold for antiviral therapy during pregnancy,optimal timing for start and discontinuation of antivirals,and the drug safety of fetuses/infants,require further investigations to optimize the antiviral therapy during pregnancy.The proof of safety of fetal exposure to antivirais needs more evidence,which can be achieved from the real-world data analysis.

Successful treatment of infantile hepatitis B with lamivudine: A case report

BACKGROUND How to treat infantile hepatitis B virus(HBV)infection remains a controversial issue.The nucleoside analogue lamivudine(LAM)has been approved to treat children(2 to 17 years old)with chronic hepatitis B.Here,we aimed to investigate the benefit of LAM treatment in infantile hepatitis B.CASE SUMMARY A 4-mo-old infant born to a hepatitis B surface antigen(HBsAg)-positive woman was found to be infected by HBV during a health checkup.Liver chemistry and HBV seromarker tests showed alanine aminotransferase of 106 U/L,HBsAg of 685.2 cut-off index,hepatitis B“e”antigen of 1454.0 cut-off index,and HBV DNA of>1.0×10^(9) IU/mL.LAM treatment(20 mg/d)was initiated,and after 19 mo,serum HBsAg was entirely cleared and hepatitis B surface antibody was present.The patient received LAM treatment for 2 years in total and has been followed for 3 years.During this period,serum hepatitis B surface antibody has been persistently positive,and serum HBV DNA was undetectable.CONCLUSION Early treatment of infantile hepatitis B with LAM could be safe and effective。

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 Cl 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.

妊娠合并HIV/AIDS 53例临床分析

目的:为进一步探讨艾滋病(AIDS)/人类免疫缺陷病毒(HIV)感染的母婴垂直传播阻断措施。方法:回顾性分析2005年1月～2009年12月我院收治53例妊娠合并HIV/AIDS患者,对孕产期阻断母婴传播措施方面进行临床分析。结果:53例中31例足月妊娠住院分娩,22例行终止妊娠手术,分娩的32例婴儿,随访率100%,≥18月龄的婴儿检测HIV抗体阳性1例,(婴儿HIV感染者),垂直传播率3.45%。结论:HIV感染的妇女妊娠,阻断艾滋病母婴传播最好方法为综合抗病毒治疗+安全助产(择期剖宫产)+人工喂养。自愿咨询与检测(VCT)是发现HIV阳性孕产妇的重要关卡,只有孕早期前发现,才能更好的采取综合预防干预措施。