Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus

Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.

A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus

AIM： To determine the therapeutic effect of lamivu- dine in late pregnancy for the interruption of motherto-child transmission （MTCT） of hepatitis B virus （HBV）. METHODS： Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials （RCTs） with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen （HBsAg）, hepatitis B e antigen （HBeAg） or HBV DNA had been documented. The relative risks （RRs） for inerruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval （CI） to estimate the efficacy of lamivudine treatment. RESULTS： Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 （95% CI, 0.25-0.76; 8 RCTs; Phet- erogeneity= 0.04） and 0.33 （95% CI, 0.23-0.47; 6 RCTs; Pheterogeneity = 0.93） indicated by newborn HBsAg or HBV DNA. The RR was 0.33 （95% CI, 0.21-0.50; 6 RCTs; Pheterogeneity = 0.46） and 0.32 （95% CI, 0.20-0.50; 4 RCTs; Pheterogeneity = 0.33） indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR （lamivudine vs hepatitis B immunoglobulin） was 0.27 （95% CI, 0.16-0.46; 5 RCTs; Pheterogeneity = 0.94） and 0.24 （95% CI, 0.07-0.79; 3 RCTs; Pheterogeneity = 0.60） indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load 〈 106 copies/mL after lamivudine treatment, the efficacy （RR, 95% CI） was 0.33, 0.21-0.53 （5 RCTs; Pheterogeneity = 0.82） for the interruption of MTCT, however, this value was not significant if maternal viral load was 〉 106 copies/mL after lamivudine treatment （P = 0.45, 2 RCTs）, as indicated by newborn serum HBsAg. The RR （lamivudine initiated from 28 wk of gestation vs control） was 0.34 （95% CI, 0.22-0.52; 7 RCTs; Pheterogeneity = 0.92） and 0.33 （95% CI, 0.22-0.50; 5 RCTs; Pheterogeneity = 0.86） indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls （P = 0.97）. Only one study reported side effects of lamivudine in newborns. CONCLUSION： Lamivudine treatment in HBV carrier- mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to 〈 106 copies/mL by lamivudine treatment.

A randomized controlled clinical trial: Interruption of intrauterine transmission of hepatitis B virus infection with HBIG

AIM： To evaluate the efficacy of interruption of intrauterine infection of HBV with HBIG in pregnant women with positive HBeAg and HBsAg.METHODS： A prospective randomized controlled trial was adopted. Sixty cases with positive HBeAg and HBsAg were coincident with the criteria of inclusion, and 8 cases were excluded. Fifty-two cases were analyzed （28 cases in trial group and 24 in control group）. All cases in trial group received 200 IU HBIG intravenously every 4 wk for 3 times from the 28^th wk. The cases of control group received placebo in the same way. All pregnant women were detected for HBeAg and HBV-DNA at the beginning of the trial and end of the trial （delivery）. The cord blood of all newborns were collected for detecting HBeAg and HBV-DNA simultaneously.RESULTS： For investigation of HBeAg of newborns in trial group, 6 of 28 cases of newborns had positive HBeAg, the HBeAg positive rate being 21.4%, the total rate of 95% CI being 8%-41%. In control group, 19 of 24 cases of newborns had positive HBeAg, HBeAg positive rate was 79.2%, the rate of 95%CI being 5%-93%. By statistical analysis, 2= 17.26, P 〈 0.01, RR = 0.27, 95% CI （6.3 × 10^-6, 8.6 × 10^-5）. For investigation of HBV-DNA of newborns in trial group, 7 of 28 cases of newborns had positive HBV-DNA, HBV-DNA positive rate being 25%, the total rate of 95% CI being 11%-45%. In control group, 20 of 24 cases of newborns had positive HBV-DNA, HBV-DNA positive rate was 83.3%, the total rate of 95% CI being 63%-95%. By statistical analysis, X^2 = 17.62, P 〈 0.01, RR = 0.30, 95% CI （1.5 × 10^-5, 1.7× 10^-4）. The results indicated that there was significant difference in HBeAg positive rate and HBV-DNA positive rate of newborns between the two groups. In trial group, 7 of 28 newborns had HBV-DNA positive, but the HBV-DNA load of newborns was lower than that of their mothers. In control group, 20 of 24 newborns still had HBV-DNA positive, and the HBV-DNA load of newborns was close to those of their mothers. Statistical analysis indicated that there was no significant difference in HBV- DNA load between postnatal women without HBIG intervention and their filial generations （T = 81.5, P 〉 0.1）. CONCLUSION： It is effective and safe to prevent intrauterine infection of HBV with HBIG from the 28^th wk in pregnant women with positive HBeAg and HBsAg. In clinical application, those pregnant women with negative HBeAg and positive HBV-DNA also need to be interrupted by HBIG.

Virologic characteristics of hepatitis B virus in patients infected via maternal-fetal transmission

AIM: To determine whether HBV with the same characteristics causes dissimilar mutations in different hosts. METHODS: Full-length HBV genome was amplified and linked with pMD T18 vector. Positive clones were selected by double-restriction endonuclease digestion (EcoRⅠ and HindⅢ) and PCR. Twenty seven clones were randomly selected from an asymptomatic mother [at two time points: 602 (1 d) and 6022 (6 mo)] and her son [602 (S)], and the phylogenetic and mutational analysis was performed using BioEditor, Clustal X and MEGA software. Potential immune epitopes were determined by the Stabilized Matrix Method (SMM), SMM-Align Method and Emini Surface Accessibility Prediction. RESULTS: All of the 27 sequences were genotype C, the divergence between the mother and son was 0%-0.8%. Compared with another 50 complete sequences of genotype C, the mother and her son each had 13 specific nucleotides that differed from the other genotype C isolates. AA 1-11 deletion in preS1 was the dominant mutation in the mother (14/18). The 1762T/1764A double mutation existed in all clones of the mother, 3 of them were also coupled with G1896A mutation, but none were found in the son.17 bp deletion starting at nucleotide 2330 was the major mutation (5/9) in the son, which caused seven potential HLA class Ⅰ epitopes and one B cell epitope deletion, and produced a presumptive new start codon, downstream from the original one of the P gene. CONCLUSION: The HBV strain in the son came from his mother, and discrepant mutation occurred in the mother and her son during infection.

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 faceto-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.

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.

Epidemiology and transmission of hepatitis B and C viruses in Kazakhstan

AIM: To investigate the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the two major ethnic groups in Kazakhstan. METHODS: A cross-sectional prospective study of HBV and HCV seroprevalence was performed among individuals born in Kazakhstan with no history of chronic hepatitis or liver disease. RESULTS: There were 290 volunteers (140 Russians and 150 Kazakhs) aged 10 to 64 years, males accounted for 46%. Active HBV infection (HBsAg positive) was present in 3.8%, anti-HBc in 30%. The prevalence was similar in females and males (33% vs 25%) (P = 0.18). The prevalence of anti-HBc increased from 19% in 10-29 years old volunteers to 53% in 50-years and older volunteers. The prevalence of HBV infection was higher in married than in single adults (38% vs 26%, respectively) (P = 0.2) and more common in Kazakhs (35%) than in Russians (24%) (P = 0.07). HCV infection was present in 9 subjects (3.2%), 5 of them also were positive for anti-HBc in the absence of HBsAg. CONCLUSION: The frequency of active HBV infection (3.8%) coupled with a high prevalence of HBV exposure in those > 50 years of age increases with age, which suggests that horizontal transmission likely relates tothe use of contaminated needles. The low prevalence of HCV infection suggests that HBV and HCV are acquired differently in this group of subjects.

Applicability and efficacy of a model for prevention of perinatal transmission of hepatitis B virus infection:Single center study in Egypt

AIM: To identify possible maternal risk factors for hepatitis B virus (HBV) acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen (HBsAg) positive mothers.

Basic Study Hepatitis B virus detected in paper currencies in a densely populated city of India: A plausible source of horizontal transmission?

BACKGROUND The recent rise in the incidence of hepatitis B virus(HBV)infections in a densely populated city of eastern India(“mixing vessel”of people of varied socioeconomic and immune status)prompted this study.Applying saliva on fingers for enumerating bank notes is a common practice in the Indian subcontinent.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin.AIM To investigate whether paper currencies could be a plausible mode of horizontal transmission of HBV infection.METHODS Polymerase chain reactions(PCR)followed by nucleotide sequencing was done for the detection of HBV.Hepatitis B virus surface antigen enzyme-linked immunosorbent assay(HBsAg ELISA)was performed on all HBV deoxyribonucleic acid-positive samples to check the detectability of the virus.Atomic force microscopy(AFM)was carried out for visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.RESULTS HBV-specific PCRs on pellets obtained after ultracentrifugation/immunoprecipitation of the currency paper washings detected potentially intact/viable HBV(genotype D2)in 7.14%of samples(n=70).AFM gave the visual confirmation of HBV particles in ultracentrifuged/immunoprecipitated samples from currency paper washings.However,HBV isolates from the currency notes could not be detected by HBsAg ELISA.CONCLUSION It is a common practice in the Indian subcontinent to count paper currencies by applying saliva on fingertips.Paper notes may be a potential source of“horizontal”transmission of this virus,especially if there are cuts/bruises on the oral mucous membrane or skin,but it was practically not possible to demonstrate experimentally such transmission.Detection of potentially intact/viable and“occult”HBV from currency poses potential risk of silent transmission of this virus among the general population.

Prevalence of transfusion transmissible infections among various donor groups:A comparative analysis

BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood transfusions.Worldwide,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/HBV.Studies highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic HBV.Globally,millions of blood donations take place annually,emphasizing the importance of maintaining blood safety.AIM To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor groups.METHODS The study assessed the prevalence of TTIs among different blood donor groups in Delhi,India.Groups included total donors,in-house donors,total camp donors,institutional camp donors,and community camp donors.Tests for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card methods.The prevalence of HBV,HCV,HIV,and syphilis,expressed as percentages.Differences in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in Delhi.The overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,respectively.In-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the lowest TTI prevalence at 0.921%.Statistical analysis revealed significant differences in overall TTI prevalence,with total and in-house donors exhibiting higher rates compared to camp donors.CONCLUSION Ongoing monitoring and effective screening programs are essential for minimizing TTIs.Customizing blood safety measures for different donor groups and studying socio-economic-health factors is essential to improving blood safety.

Studies on the integration of hepatitis B virus DNA sequence in human sperm chromosomes

Aim: To study the integration of hepatitis B virus (HBV) DNA into sperm chromosomes in hepatitis B patients and the features of its integration. Methods: Sperm chromosomes of 14 subjects (5 healthy controls and 9 HB patients, including 1 acute hepatitis B, 2 chronic active hepatitis B, 4 chronic persistent hepatitis B, 2 HBsAg chronic carriers with no clinical symptoms) were prepared using interspecific in vitro fertilization between zona-free hamster oocytes and human spermatozoa. Fluorescence in situ hybridization (FISH) to sperm chromosome spreads was carried out with biotin-labeled full length HBV DNA probe to detect the specific HBV DNA sequences in the sperm chromosomes. Results: Specific fluorescent signal spots for HBV DNA were seen in sperm chromosomes of one patient with chronic persistent hepatitis B. In 9(9/42) sperm chromosome complements containing fluorescent signal spots, one presented 5 obvious FISH spots and the others 2 to 4 signals. The fluorescence intensity showed significant difference among the signal spots. The distribution of signal sites among chromosomes seems to be random. Conclusion: HBV could integrate into human sperm chromosomes. Results suggest that the possibility of vertical transmission of HBV via the germ line to the next generation is present.

Perinatal transmission in infants of mothers with chronic hepatitis B in California

To evaluate maternal hepatitis B virus (HBV) DNA as risk for perinatal HBV infection among infants of HBV-infected women in California. METHODSRetrospective analysis among infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received post vaccination serologic testing (PVST) between 2005 and 2011 in California. Demographic information was collected from the California Department of Public Health Perinatal Hepatitis B Program databaseand matched to birth certificate records. HBV DNA level and hepatitis B e antigen (HBeAg) status were obtained from three large commercial laboratories in California and provider records if available and matched to mother infant pairs. Univariate analysis compared infected and uninfected infants. Multivariate analysis was restricted to infected infants and controls with complete maternal HBV DNA results using a predefined high HBV DNA level of > 2 × 107 IU/mL, a 5:1 ratio of cases to controls and a two-sided confidence level of 95%. RESULTSA total of 17687 infants were born to HBsAg positive mothers in California between Jan 1 2005 and Dec 31, 2011. Among 11473 infants with PVST, only 125 (1.1%) were found to be HBV infected. Among these infected infants, lapses in Advisory Committee on Immunization Practices recommended post exposure prophylaxis (PEP) occurred in only 9 infants. However, PEP errors were not significantly different between infected and uninfected infants. Among the 347 uninfected and infected infants who had maternal HBeAg and HBV DNA level, case-control analysis found HBeAg positivity (70.4% vs 28.9%, OR = 46.76, 95%CI: 6.05-361.32, P < 0.001) and a maternal HBV DNA level ≥ 2 × 107 IU/mL (92.6% vs 18.5%, OR = 54.5, 95%CI: 12.22-247.55, P < 0.001) were associated with perinatal HBV infection. In multivariate logistic regression, maternal HBV DNA level ≥ 2 × 107 IU/mL was the only significant independent predictor of perinatal HBV infection. CONCLUSIONIn California, transmission is low and most infected infants receive appropriate PEP and vaccination. Maternal HBV DNA ≥ 2 × 107 IU/mL is associated with high risk of perinatal infection.

Hepatitis B virus lineages in mammalian hosts:Potential for bidirectional cross-species transmission

The hepatitis B virus(HBV)is a cosmopolitan infectious agent currently affecting over 350 million people worldwide,presently accounting for more than two billion infections.In addition to man,other hepatitis virus strains infect species of several mammalian families of the Primates,Rodentia and Chiroptera orders,in addition to birds.The mounting evidence of HBV infection in African,Asian and neotropical primates draws attention to the potential crossspecies,zoonotic transmission of these viruses to man.Moreover,recent evidence also suggests the humans may also function as a source of viral infection to other mammals,particularly to domestic animals like poultry and swine.In this review,we list all evidence of HBV and HBVlike infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species.

Risks of Viral Hepatitis B Transmission in Mother-to-Infant of Pregnant Women Carriers of Chronic Viral Hepatitis B in Cote d’Ivoire

The aim of this study was to identify the risk factors of mother-to-child transmission of HBV in positive Ag Hbs pregnant women in Cote d’Ivoire. Methods: This was a transversal prospective study that took place over a period of 7 months (from February 2016 to August 2016) in 2 university hospital and 2 private clinics. We consecutively recruited 91 pregnant women who were positive for HBs Ag in prenatal consultations. For each pregnant woman record included in the study, we provided Socio-demographic (Age, marital status, education level, social rank, gravidity, parity) and biological data (HBs Ag, Anti-HBc Total Ac, Hbe Ag, Ac anti-Hbe Ac, DNA-VHB, Ac anti-HCV Ac, retroviral serology, transaminases). All of these data were collected using a survey sheet developed for the study. Results: The age of our pregnant women HBs positive ranged from 18 years to 44 years with a mean age of 30.10 years. The age group from 20 to 39 years was the most represented with a frequency of 92.31%. Almost of all positive HBs Ag pregnant women was HBe Ag negative, only 3.3% was HBe Ag positive. The viral load above 2000 IU/ml was found in 21 (23.03%) patients. There were 4 co-infected patients, which 3 HBV-HIV and 1 HBV-HCV. Only 19 (20.88%) pregnant HBs Ag positive women were able to bring back the supplementary virological assessment within a period less than one month. Conclusion: According to our work the virologic profile of positive HBs Ag in pregnant women in Cote d’Ivoire is characterized by an important viral replication objectified by a high viral load in about 23% pregnant women, a negativity of HBe antigen in 96.6% of them.

Mutation analyses of integrated HBV genome in hepatitis B patients

Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers （HBF） and their children. In this study, we used nest polymerase chain reaction （PCR）, fluorescence in situ hybridization （FISH）, and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBE and in peripheral blood mononuclear cells （PBMC） from 74 cases of HBFs and their children who were born after their fathers＇ HBV infection （caHBF）. We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBE It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBE This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.

Comprehensive review of telbivudine in pregnant women with chronic hepatitis B

AIM:To achieve an evidence-based conclusion regarding the safety and efficacy of telbivudine during pregnancy.METHODS:A pooled analysis of data from a literature search reported 1739 pregnancy outcomes(1673 live births)from 1725 non-overlapping pregnant women treated with telbivudine.The prevalence of live birth defects(3.6/1000)was similar to that of the nonantiviral controls(3.0/1000)and not increased as compared with overall prevalence(14.5 to 60/1000).No target organ toxicity was identified.The prevalence of spontaneous abortion in pregnant women treated with telbivudine(4.2/1000)was not increased compared with the overall prevalence(16/1000).The mother-to-child transmission rate was significantly reduced in pregnant women treated with telbivudine(0.70%)compared to those treated with the non-antiviral controls(11.9%;P<0.0001)or compared to the historical rates of hepatitis B virus(HBV)-infected population without antiviral treatment(10%-15%).RESULTS:Cumulatively 489 pregnancy cases have been reported in the telbivudine pharmacovigilance database(with a cut-off date 31 August 2014),of those,308 had known pregnancy outcomes with 249 cases of live births(239 cases of live birth without congenital anomaly and 10 cases of live birth with congenital anomaly).In the latest antiretroviral pregnancy registry report(1 January 1989 through 31 January 2015)of27 patients exposed to telbivudine during pregnancy(18,6 and 3 during first,second and third trimester,respectively)19 live births were reported and there were no cases of birth defects reported.CONCLUSION:Telbivudine treatment during pregnancy presents a favorable safety profile without increased rates of live birth defects,spontaneous abortion or elective termination,or fetal/neonatal toxicity.Exposure to telbivudine in the first,second and third trimester of pregnancy has been shown to significantly reduce the risk of HBV transmission from mother to child on the basis of standard immune prophylaxis procedure.

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。

Management of chronic hepatitis B in pregnancy

Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in thechild-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B

BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

Risk Factors, Clinical Features, Baseline Alanine Aminotransferase and CD4+ Count of Children with HIV Co-Infection with Hepatitis B and C at a Tertiary Hospital in Southwest Nigeria

Background: Human immunodeficiency virus and hepatitis B and C viruses are endemic in sub- Saharan African countries including Nigeria. Researchers have studied the burden of co-infection of HIV with hepatitis B and hepatitis C but the risk factors and clinical presentation have not been much addressed especially in children. Methodology: This was a prospective cross sectional study that determined the prevalence, risk factors, clinical features, baseline CD4+ count, CD4+ percentage, and alanine aminotransferase (ALT) of newly diagnosed, HAART na?ve HIV co-infection among children who were managed at a Tertiary Hospital in Ilorin, Nigeria. Result: Of the 60 HIV- infected children recruited, 11.7% had HIV co-infection with HBV or HCV. Children with co-infec- tions (mean age 8.43 ± 2.37 years) were significantly older than their HIV mono-infected counterparts (mean age 5.25 ± 3.96 years) (p = 0.011). There was no significant difference between HIV monoinfection and HIV co-infection with respect to gender (p = 0.758), ethnicity (p = 0.707), religion of parents (p = 0.436), family type (p = 0.184), social class (p = 0.535), previous transfusion (p = 0.053), scarification (p = 0.612), female genital mutilation (p = 0.778), and sharing of clippers (p = 0.806). The mean BMI, immunological staging (p = 0.535), baseline ALT (p = 0.940), and mean baseline CD4+ count (p = 0.928) were comparable. However, the body mass index of HIV co-infec- ted children decreased with age up till age 10 years. Conclusion: There were no risk factors, nor clinical features predictive of co-infection identified in this study. Co-infection did not negatively impact baseline, CD4+ count and ALT.