Article

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of Hepatitis B Virus.

Authors:
  • Institute for Liver and Digestive Health
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Abstract

Perinatal transmission of Hepatitis B Virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, baseline viral load mean 7.8 log IU/mL (+/- 0.72) and ALT median 25 U/L (18.75-33). Duration of AVT before birth was mean 58 days (+/- 19) TDF and 53 (+/- 14) lamivudine. Viral load declined by 3.64 log IU/mL (+/- 0.9) TDF and 2.81 log IU/mL (+/- 1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3 and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to two and zero% in TDF and lamivudine cohorts, compared with 20% in untreated. TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.

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... 12,13 Current studies involving HBV-infected women and their infants reported only short-term outcomes no longer than 1 year after birth. [14][15][16][17] Long-term safety data for children is anticipated but is insufficient. 9 In this study, we reported the renal function, long-term growth parameters, as well as bone development assessed by BMD measurements and serum markers related to bone metabolism, of the children born to HBV-infected mothers with and without TDF treatment from 30-32 gestational weeks until 1 month postpartum in a prospective, multisite trial. ...
... 15 Children with prenatal exposure to TDF had comparable growth, renal function, and bone development as those who were unexposed to TDF. In addition to the short-term safety data from previous reports, [14][15][16][17] our data provide evidence to support the use of TDF during late pregnancy, demonstrating the long-term safety of TDF with respect to childrens' growth, renal function and bone development. ...
... throughout the entire pregnancy, and might receive multiple antiviral drugs in addition to TDF, 13,23,31,32 HBV-infected pregnant women usually use TDF as monotherapy during late pregnancy to prevent maternal transmission. [14][15][16][17] Longer treatment duration and possible confounding factors, such as use of other antiviral drugs, co-morbidities, and diverse study participants from different sites/countries may result in the difference in neonatal bone mineral content in the study of HIV-infected pregnant women and their infants. 13 Our prospective longitudinal follow-up data show similar increasing BMD trends with age and comparable bone metabolism markers in both the TDF and control group of children aged 2-7 years. ...
Article
Background & aims: Long-term safety outcome of children with fetal exposure to tenofovir disoproxil fumarate (TDF) to prevent maternal transmission of hepatitis B virus (HBV) is lacking. Methods: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visit once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. Results: One hundred and twenty-eight children, 71 in TDF and 57 in control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, P = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, P = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73mˆ2, P = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in TDF and control group had comparable levels of serum calcium (2.61 ± 0.02 vs. 2.57 ± 0.02 mmol/L, P = 0.115), phosphorus (5.29 ± 0.05 vs. 5.23 ± 0.05 mg/dL, P = 0.379), bone specific alkaline phosphatase (64.22 ± 1.68 vs. 63.35 ± 1.90 μg/L, P = 0.736), calcidiol (33.25 ± 0.70 vs. 32.82 ± 0.80 ng/mL, P = 0.687) and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cmˆ2, P = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cmˆ2, P = 0.926). Conclusions: Children of HBV mothers with and without TDF treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.
... Although studies conducted in Australia, Canada and France (N = 239/312, 77% Asian) included multiparous HBV NA-treated patients, few report long-term maternal outcomes or the outcomes of tenofovir therapy in consecutive pregnancies. 11,13,14 Immune reconstitution post-partum can increase host immune-mediated flares to viral antigens, that is potentially exacerbated following withdrawal of TDF. 15,16 Most studies found that NA therapy in late pregnancy followed by treatment withdrawal early post-partum was associated with ALT flare but reported variable changes in HBV DNA levels or rates of HBeAg seroconversion during immediate post-partum up to 1 year of follow-up. ...
... Other large multicentre studies 9,25,26 and metaanalyses 8,27 including Asian studies were conducted in Taiwan (tenofovir Previous studies have reported that tenofovir treatment in pregnancy was not associated with nephrotoxicity or significant changes in serum phosphate levels. 9,11,13,18 Similarly, none of the tenofovir-treated patients in this study developed renal function impairment. There are reassuring safety data on infants born to hepatitis B mothers treated with tenofovir during pregnancy. ...
... There are reassuring safety data on infants born to hepatitis B mothers treated with tenofovir during pregnancy. [8][9][10][11][12][13]18,[25][26][27]33 However, recent data have demonstrated a lower bone mineral content in newborns of women with HIV infection who were exposed to tenofovir in late pregnancy despite adjustment for factors expected to affect neonatal bone mineral content. 34 The majority of infants assessed were successfully immunised against HBV in our study. ...
Article
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Background: There are limited long-term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)-treated women during pregnancy. Aims: To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post-partum in a low HBV endemic region. Methods: Retrospective real-world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post-partum. Results: In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7-39.5) post-partum, 19% (65/341) received TDF (11 initiated pre-pregnancy, 53 for mother-to-child transmission (MTCT) prevention). During follow-up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re-treated. In all TDF-treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow-up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post-partum, requiring re-treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post-partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post-partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23-40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12-26) post-partum. Conclusions: Post-partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long-term follow-up.
... 23 Furthermore, most of the previous studies started TDF treatment in the third trimester. 1,2,5,6,10,11,20,21,[24][25][26][27][28] However, data regarding the efficacy and safety in mothers whose treatment commenced in the second trimester (24-27 weeks) are sparse. Whether TDF treatment initiated from the second trimester has advantages over TDF treatment starting from the third trimester in highly viraemic pregnant women is not clear. ...
... log10 IU/mL (baseline-delivery) in pregnant women who started TDF treatment at 32 weeks of gestation and discontinued at 12 weeks postpartum. 24 In our study, the reductions of HBV DNA (baseline-delivery) were 4.8±1.2 log10 IU/mL in patients who started the TDF treatment from the second trimester (24-27 weeks) and 4.3±1.1 log10 IU/mL in the third trimester group (28-30 weeks). ...
Article
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Purpose: To investigate whether tenofovir disoproxil fumarate (TDF) treatment that started from the second trimester had an advantage over TDF treatment that started from the third trimester. Patients and methods: Twenty 35-year-old pregnant women with hepatitis B virus (HBV) DNA >2×106 IU/mL were prospectively enrolled in this study. All participants were divided into two subgroups: the second trimester group who started TDF treatment at 24-27 weeks and the third trimester group who started TDF treatment at 28-30 weeks. The primary outcome was the change in serum HBV DNA level from baseline to delivery. Each parameter was tested every 4 weeks from TDF initiation to 3 months postpartum. Results: There were 80 pregnant women in the second trimester group and 49 pregnant women in the third trimester group. The decline in HBV DNA from baseline to delivery was more obvious in the second trimester group (4.8±1.2 log10 IU/mL) than that in the third trimester group (4.3±1.1 log10 IU/mL, p=0.041). The downward shift of haemoglobin (HB) from baseline to delivery was greater in the second trimester group (10.6±10.7 g/L) than in the third trimester group (6.3±12.3 g/L, p=0.041). The decline in HBV DNA from baseline to delivery was linearly related to the start of TDF treatment from the second trimester (β=0.50 and 95% CI: 0.26-0.75, p<0.001). There were no significant differences between the two groups regarding HBV serologic markers and safety indicators. Conclusion: Starting TDF treatment from the second trimester achieved better viral suppression than starting TDF treatment from the third trimester in highly viraemic pregnant women without increasing additional adverse reactions. HB level needed frequent monitoring during treatment to avoid anaemia. Registry number: Clinical Trial No. NCT02719808.
... Previous studies have reported that antiviral therapy with tenofovir can substantially reduce perinatal transmission of HBV in mothers with high viral load (Greenup et al., 2014;Hyun et al., 2017;Jourdain et al., 2016Jourdain et al., , 2018Thilakanathan et al., 2018;) and is a cost-effective treatment . Jourdain et al. reported that MTCT is rare when passive/active immunization is done timely (Jourdain et al., 2018). ...
... Moreover, in our study, maternal liver function was stable and viral control was good during pregnancy, there were no preterm delivery or abortion occurred in our study, and the Apgar scores of the newborns were also normal after birth. Therefore, we concluded that the use of telbivudine or tenofovir after 24 weeks of pregnancy was safe and effective, which was similar to the results of previous studies (Greenup et al., 2014;Han et al., 2011;Hyun et al., 2017;Jourdain et al., 2016;Lu et al., 2014;Pan et al., 2012;Thilakanathan et al., 2018;Wu et al., 2015). ...
Article
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To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12–24, 28–32, and 36–40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA). Compared with baseline (12–24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36–40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36–40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log10 (HBV DNA) increased from 3.38 (2.00–7.30) to 7.43 (4.68–8.70). In tenofovir group, log10 (HBV DNA) decreased from 7.52 (3.32–8.70) to 2.98 (2.00–5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
... HBV is primarily transmitted vertically from mother to child, particularly in endemic countries [6]. Efforts to reduce the maternal to child transmission (MTCT) have focused on vaccination in newborns of infected mothers and administration of human immunoglobulin (HBIg) at birth [7]. While these measures have been largely successful, MTCT can still occur [8], particularly in mothers who are HBeAg-positive and/or have high viral loads. ...
... While these measures have been largely successful, MTCT can still occur [8], particularly in mothers who are HBeAg-positive and/or have high viral loads. There is now strong evidence suggesting MTCT can be further reduced by treating these mothers with tenofovir in the third trimester of pregnancy to reduce the viral load at the time of birth [7,8]. ...
Article
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Purpose of Review As we strive to reach the World Health Organization (WHO) goal of eliminating viral hepatitis as a public health threat by 2030, point of care tests (POCTs) will be important in low- to middle-income and developed countries. This review aims to investigate available POCT choices for hepatitis B virus (HBV) and to provide an algorithm for screening, assessing, and monitoring chronic HBV. Recent Findings There are 3 WHO pre-qualified rapid diagnostic assays for hepatitis B surface antigen (HBsAg) that are sensitive, specific, and reliable in screening for HBV: SD Bioline, Determine 2, and VIKIA. POCTs for other biomarkers are less reliable and sensitive but have some applicability. The Xpert® HBV Viral Load assay is sensitive and specific with a wide dynamic range. Summary While POCT for HBeAg and HBV antibodies require improvement, HBsAg POCT and the Xpert® HBV Viral Load assay are reliable and available now.
... From these studies, there were 15 groups treated with LAM, 17 groups treated with LdT, 4,6-9,15-26 and 12 groups treated with TDF. 16,24,[26][27][28][29][30][31][32][33][34][35] Some of them covered more than one NA (n = 7). 7,15,16,24,26,28,31 Contrary to relatively older studies, the majority of recent studies did not cover LAM. ...
... 16,24,[26][27][28][29][30][31][32][33][34][35] Some of them covered more than one NA (n = 7). 7,15,16,24,26,28,31 Contrary to relatively older studies, the majority of recent studies did not cover LAM. In all studies for the group under treatment, antiviral therapy was initiated in the second or third trimester, while discontinuance occurred at different times. ...
Article
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Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF). Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019. Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT's high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included. Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.
... We found both TDF and LdT were 100% successful to prevent MTCT in our real-life setting. Similar to the previous studies [8][9][10][16][17][18] , our data further support the use of TDF, or LdT during late pregnancy on preventing MTCT in CHB mothers with high levels of HBV DNA [8][9][10][16][17][18] . ...
... We found both TDF and LdT were 100% successful to prevent MTCT in our real-life setting. Similar to the previous studies [8][9][10][16][17][18] , our data further support the use of TDF, or LdT during late pregnancy on preventing MTCT in CHB mothers with high levels of HBV DNA [8][9][10][16][17][18] . ...
Preprint
Full-text available
Background: Little data exist regarding comparison of efficacy and safety between tenofovir disoproxil fumarate (TDF) and Telbivudine (LdT) in late pregnancy to prevent hepatitis B mother-to-child transmission (MTCT) in real-world settings. Methods: We retrospectively included HB-s antigen (HBsAg) positive mothers with HBV DNA ≥2*10⁵IU/mL to receive TDF or LdT after gestational weeks 24~32 weeks. All infants received standard immunoprophylaxis. Primary outcomes were MTCT rates at infants’ age of 52 weeks and safety of TDF or LdT use. Secondary outcomes were the decline of HBV-DNA levels at delivery and rates of on-treatment and off-treatment alanine aminotransferase (ALT) elevation>2 upper limits of normal (ULN) during the study. Results: Of 1407 women, 209 received TDF and 1198 received LdT treatment. There were no differences between mean duration of TDF and LdT treatment (TDF vs. LdT: 11.76±2.20 weeks vs 11.64±2.79 weeks, p=0.47). At birth, 213 (9.8%) infants in the TDF-group were HBsAg positive, lower than 1180 (20.8%) in the LdT-group (p<0.001). Among 1405 infants (TDF/LdT=213/1192) of the 1385 (TDF/LdT=205/1180) women completed the 52-weeks study, intention‐to‐treat analysis indicated one infant (0.5 %) was lost to follow-up in TDF treated mothers and three (0.3 %) in LDT treated mothers (p=0.48). On-treatment analysis indicated no HBsAg positive infants in the two groups. Levels of HBV-DNA decline in TDF-treated mothers were observed comparable to LdT-treated mothers (4.05±0.93 log10IU/mlvs.3.99±1.30 log10IU/ml, p=0.50). TDF-treated mothers had complained more symptoms of the digestive system and less arthralgia than LdT-treated mothers. All adverse events in the two groups were grade I-II. Alanine aminotransferase (ALT) elevation(>2ULN) in TDF-treated mothers were lower than in LdT-treated mothers (7.3% vs.15.7%, p<0.05). Conclusions: TDF and LdT use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. However, TDF has fewer ALT abnormalities than LdT during treatment and is the preferred choice.
... The mother-to-child transmission (MTCT) route accounts for the majority of HBV transmission in China, and more than 90% of infants born to mothers with hepatitis B e antigen (HBeAg) develop chronic HBV infection (CHB) [3,4]. Immunoprophylaxis with hepatitis B immunoglobin (HBIG) and HBV vaccine reduces the rate of MTCT from 90% to 10-20% [5][6][7]. Previous studies indicated that the addition of antiviral agents, such as lamivudine, telbivudine, or tenofovir disoproxil fumarate (TDF), in highly viremic mothers during the second or third trimester of pregnancy further decreased the rate of MTCT to 0-5% [5][6][7][8]. ...
... Immunoprophylaxis with hepatitis B immunoglobin (HBIG) and HBV vaccine reduces the rate of MTCT from 90% to 10-20% [5][6][7]. Previous studies indicated that the addition of antiviral agents, such as lamivudine, telbivudine, or tenofovir disoproxil fumarate (TDF), in highly viremic mothers during the second or third trimester of pregnancy further decreased the rate of MTCT to 0-5% [5][6][7][8]. ...
Article
Background Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Methods In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200,000 IU/ml who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. Results In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants’ physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. Conclusion Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.
... We found both TDF and LdT were 100% successful to prevent MTCT in our real-life setting. Similar to the previous studies [8][9][10][16][17][18] , our data further support the use of TDF, or LdT during late pregnancy on preventing MTCT in CHB mothers with high levels of HBV DNA [8][9][10][16][17][18] . ...
... We found both TDF and LdT were 100% successful to prevent MTCT in our real-life setting. Similar to the previous studies [8][9][10][16][17][18] , our data further support the use of TDF, or LdT during late pregnancy on preventing MTCT in CHB mothers with high levels of HBV DNA [8][9][10][16][17][18] . ...
Preprint
Full-text available
Background: Little data exist regarding the comparison of efficacy and safety between tenofovir disoproxil fumarate (TDF) and Telbivudine (LdT) in late pregnancy on preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. Methods: We retrospectively included HB-s antigen (HBsAg) positive mothers with HBV DNA ≥2*10⁵IU/mL to receive TDF or LdT after gestational weeks 24~32 weeks. All infants received standard immunoprophylaxis. Primary outcomes were MTCT rates at infants’ age of 52 weeks and safety of TDF or LdT use. Secondary outcomes were the decline of HBV-DNA levels at delivery and rates of on-treatment and off-treatment alanine aminotransferase (ALT) elevation>2 upper limits of normal (ULN) during the study. Results: Of 1407 women, 209 received TDF and 1198 received LdT treatment. There were no differences between mean duration of TDF and LdT treatment (TDF vs. LdT: 11.76±2.20 weeks vs 11.64±2.79 weeks, p>0.05). At birth, 213 (9.8%) infants in the TDF-group were HBsAg positive, lower than 1180 (20.8%) in the LdT-group (p<0.001). Among 1405 infants (TDF/LdT=213/1192) of the 1385 (TDF/LdT=205/1180) women completed the 52-weeks study, intention‐to‐treat analysis indicated 1 (0.5 %) (1 infant was lost to follow-up) in TDF treated mothers and 3(0.3 %) in LDT treated mothers (3 infants were lost to follow-up). There was no difference between TDF group and LdT (p=0.483). On-treatment analysis indicated 0% HBsAg positive infants in the two groups (p=1.0). Levels of HBV-DNA decline in TDF-treated mothers were observed comparable to LdT-treated mothers (4.05±0.93 log10IU/mlvs.3.99±1.30 log10IU/ml, p=0.499). TDF-treated mothers had complained more symptoms of the digestive system and less arthralgia than LdT-treated mothers. All adverse events of two groups were grade I-II. Alanine aminotransferase (ALT) elevation(>2ULN) in TDF-treated mothers were lower in TDF-treated mothers than LdT-treated mothers (7.3% vs.15.7%, p<0.05). Alanine aminotransferase flares in TDF-treated mothers were observed lower than LdT-treated mothers (7.3% vs.15.7%, p< 0.05). Conclusions: TDF and LdT use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. Although complained more digestive system symptoms, TDF treated mothers had fewer ALT abnormalities than LdT.
... There are no adequate and well-controlled studies of LAM (Lamividune), ADV (Adefovir), and ETV (Entecavir) in pregnant women [1]. Reproduction studies in animals and humans with TDF (Tenofovir Disoproxil Fumarate) and telbivudine (LdT) support that no there is no harm to the fetus due to these drugs [1]; although TDF should be the first choice, because of its better resistance profile and more extensive safety data in pregnant HVB positive [18][19][20]. ...
... Among the selected studies, 3 RCTs [7-9] and 12 non-RCTs [10,[16][17][18][19][20][21][22][23][24][25][26] compared treatment started in the third trimester versus control, 7 non-RCTs compared the timing of second trimester versus control [27][28][29][30][31][32][33], 3 non-RCTs compared first trimester versus control [14,34,35], 4 non-RCTs compared second and third trimester versus control respectively [11,[36][37][38], 3 non-RCTs compared first, second trimester versus control respectively [39][40][41]; 2 non-RCTs compared first, third trimester versus control respectively [12,42], 1 non-RCTs compared first, second trimester, third trimester versus control respectively [13]. No randomized controlled trials were conducted for the treatment that was applied during first or second trimester except for several non-RCTs. ...
Article
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Background Several antiviral agents licenced for blocking mother-to-child transmission (MTCT) of HBV, but their relative efficacy beginning from different trimesters has scarce been evaluated. We aimed to conduct a network meta-analysis to statistically differ the efficacy and safety of each antiviral agents initiating on different timings in preventing mother-to-infant transmission of HBV.Methods Studies were included from PubMed, EMBASE, Web of Science, and Cochrane databases through July 1, 2019. Eligible studies recruited randomized controlled trials and nonrandomized studies reporting about infant or/and maternal efficacy and safety outcomes and were screened by two investigators independently. Extracted data were analyzed by pair-wised and network meta-analysis, respectively.Results3 Randomized and 32 nonrandomized studies enrolling 6738 pregnant female were included. Using network analysis, any antiviral agent interrupted HBV vertical transmission much more effectively than placebo. No agent showed significant efficacy different from others, but a strong trend toward significance was found in telbivudine and tenofovir, of which had the highest probability of being ranked the first- or second-best treatment for reducing MTCT of HBV. The treatment applied in the first and second trimester had a similar efficacy in preventing MTCT. Compared with the initiation during the third trimester, lower rate of MTCT was revealed when antiviral therapy was administrated before third trimester, (RR = 0.045, 95% CI 0.0053 to 0.20); a similar effect at delivery on suppressing maternal HBV DNA level and converting serum HBeAg were achieved if the timing of antiviral treatment started prior, but an obvious improvement of normalizing ALT flare was calculated out; no statistically differences among maternal and fetal safety outcomes were found if mothers received antiviral agents before pregnant 28 weeks.Conclusion This network meta-analysis recommended the earlier use of telbivudine or tenofovir, tends to be better to prevent MTCT of HBV in pregnancy with no increased adverse maternal or fetal outcomes.
... A meta-analysis showed that TDF reduced the rates of MTCT with no increased risk for any adverse reactions or unfavorable maternal or fetal outcomes (10). In another study, tenofovir significantly reduced maternal viral load with a mean reduction of 3.64 ± 0.9 log10 IU/mL and dramatically decreased the incidence of MTCT (11). Our study supports that data, sufficient viral suppression was achieved in pregnant women receiving either TDF or LTD and there no MTCT occurred. ...
Article
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p> OBJECTIVE: Implementation of strategies to prevent vertical transmission is highly important steps in reducing the global burden of chronic hepatitis B. We conducted this prospective study to observe the clinical course and outcomes of untreated and treated HBV in pregnant. STUDY DESIGN: HBsAg-positive pregnants were prospectively enrolled from 2013 to 2016 and antiviral therapy was administered to eligible patients. Pregnancy and neonatal outcomes were determined in the treated (n=29) and untreated group (n=136). Active-passive immunoprophylaxis was administered to infants and they were tested for HBsAg. RESULTS: The risk factors for transmission (HBeAg positivity, history of previously-born HBsAg-positive child) were significantly higher in the treated group. All participants under treatment had sufficient viral suppression. Half of the pregnant women for whom the treatment was withheld at the postpartum period, experienced increased viral load. The treated group had significantly higher pre- and postpartum alanine aminotransferase levels more than the untreated group, although there were no significant differences in other biochemical parameters. There were no significant differences regarding fetal outcomes between the two groups. All infants were HBsAg-negative at seven months postpartum. CONCLUSION: While the untreated group included inactive carriers, there were more patients at risk for transmission of HBV to their offsprings in the treated group. Half of the pregnant women for whom the treatment was withheld at the postpartum period, experienced increased viral load. Antiviral therapy did not adversely affect the outcomes of infants. As a result, we successfully prevented perinatal HBV transmission by close monitoring of participant pregnant women and starting antiviral therapy when needed.</p
... The results showed that TDF effectively reduced the maternal HBV viral load by (3.64 ± 0.9) log 10 IU/mL and markedly lowered the MTCT of HBV infection, which was 2% and 20% in the TDF group and untreated group, respectively. 54 The efficacy and safety of maternal TDF treatment in reducing perinatal HBV transmission were also evaluated in a prospective, multicenter trial that enrolled 118 HBsAg-and HBeAg-positive pregnant women with HBV-DNA > 7.5 log 10 IU/mL. The mothers received no medication (control group, n = 56) or TDF (TDF group, n = 62) from week 30-32 of gestation until 1 month postpartum. ...
Article
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Chronic hepatitis B virus (HBV) infection caused by mother‐to‐child transmission (MTCT, also known as vertical transmission) during the perinatal period is a major public health problem worldwide. Despite the availability of the combined active‐passive immunization with a hepatitis B vaccine and hepatitis B immunoglobulin after birth, about 9% of newborns are still infected with HBV, especially those born to hepatitis B e antigen (HBeAg)‐positive mothers. Currently, the management of HBV infection during pregnancy remains controversial. This article briefly reviews the recent advances in the epidemiology of HBV, immunization against it, and management strategies in the third trimester.
... Lamivudine, LdT and TDF are equivalent in terms of antiviral efficacy 6,26 . Hence, in our study, their effects were merged and directly compared. ...
Article
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For pregnant women with high viral load, antiviral therapy has been administered in addition to active and passive immune prophylaxis as a crucial adjunctive therapy to interrupt mother-to-child hepatitis B virus (HBV) transmission (MTCT). However, the time of antiviral therapy onset remains controversial. A systematic review and meta-analysis was conducted to compare the efficacy of antiviral therapy during the second or the third trimester for prevention of HBV vertical transmission. We searched nine databases for observational studies and randomized controlled trials that enrolled pregnant women with positive HBsAg treated with antivirals. The outcomes of interest were maternal HBV-DNA levels prior to delivery and the rates of HBV MTCT. We included nine studies that enrolled 1,502 pregnant women. The average HBV-DNA level before treatment was approximately 8 log10 copies/mL. Compared to the onset of antiviral intervention in the third trimester, the beginning of treatment in the second trimester distinctly reduced maternal predelivery HBV-DNA levels. However, no significant difference in HBV MTCT was found between the second and third trimester groups. Furthermore, the subgroup analysis showed that there were no significant differences between groups beginning treatment at different times (second or third trimester) with regard to HBV MTCT or other evaluated endpoints. For pregnant women with HBV-DNA levels less than or equal to 8 log10 copies/mL, the beginning of antiviral treatment can be delayed until the third trimester.
... In a study, it is reported that pregnant women usually well tolerate the TDF but had more gastrointestinal adverse effects. In the same study, it was reported that TDF reduced vertical transmission as expected (13). In contrast with these reports in a study conducted by Jourdain et al., it has been reported that it did not significantly reduce the vertical transmission of HBV (14). ...
... Using this strategy, NA (preferably TDF) is administered to pregnant women with HBV-DNA >200,000 IU/mL, beginning in the late second or early third trimester and continuing until delivery or postpartum; the newborn then receives standard immunoprophylaxis with HBIG and HB vaccine. A number of prospective comparative studies (37,38) and randomized controlled trials (39,40) conducted overseas have shown that TDF significantly reduced the maternal viral load and mother-to-child transmission without increasing the incidence of clinically meaningful adverse events. However, a double-blind randomized controlled trial in Thailand suggested that if mother-to-child transmission was well controlled by immunoprophylaxis alone, the additional effect of TDF was not found to be statistically significant (0% in the TDF group vs. 2% in the placebo group) (41). ...
Article
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The appropriate management of hepatitis B virus (HBV) infection during pregnancy has not been established in Japan. We herein report five HBV-infected pregnant Japanese women who received tenofovir disoproxil fumarate (TDF). Two of them had been born after the introduction of nationwide immunoprophylaxis and were vertically infected with HBV, highlighting the need to address mother-to-child transmission further. In both entecavir-experienced and nucleoside/nucleotide analog-naïve mothers, TDF suppressed HBV replication without serious adverse events. All five children were free from congenital disorders, growth impairment, and HBV infection. TDF showed safety and efficacy for pregnant woman with chronic hepatitis B and might have helped prevent mother-to-child transmission.
... Also of importance are the anti-HBV activities of most of the anti-retroviral drugs used for HIV which included lamivudine, tenofovir disoproxil fumarate (TDF), and telbivudine. The anti-retroviral drugs are known to reduce the viral load of HBV in infected pregnant women and reduce the chances of MTCT of HBV infection [19]. These services are however not available for pregnant women who are reactive or positive for HBsAg in Nigeria. ...
Article
Nigeria in the last few years succeeded in reversing HIV incidence and HIV-related deaths. This was attributed to the multi-sector response and the strengthening of maternal and child health system to specifically meet the needs of HIV/AIDS prevention and control. Despite epidemiological similarities of hepatitis B and HIV infections, hepatitis B incidence and mortalities were on the increase. An estimated 95% of individuals with viral hepatitis were unaware of their infection and so did not benefit from clinical care, treatment, and interventions that are designed to reduced transmission. We suggest that hepatitis B endemic settings adopt best practices that integrate hepatitis B prevention into HIV services at all levels of health care to reduce new infection.
... Giving hepatitis B immunoglobulin (HBIG) together with HBV birth vaccine, active/passive immunisation further reduces the risk of HBV MTCT [38,42,43], but is costly and not logistically possible in many resource-limited settings. Treating women in the third trimester of pregnancy with antiviral drugs such as lamivudine [44], tenofovir [45] or telbivudine [46] is effective in reducing HBV viral load and thus reducing the risk of transmission. Tenofovir and emtricitabine (or lamivudine) have been part of first-line antenatal antiretroviral therapy (ART) in SSA since 2010, so HIV-HBV co-infected pregnant women would have received anti-HBV therapy. ...
Article
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Background Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa. Methods Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing. Results Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive. Conclusions This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.
... For mothers who have no other indications for continuing antiviral therapy, the nucleos(t)ide analogues used to prevent transmission is suggested to stop at delivery or within 12 weeks postpartum [10,30,31]. Clinical trials of antiviral therapy during late pregnancy in highly viremic mothers showed that the rate of mother-to-infant transmission, assessed by infant's HBsAg seropositivity at 6-9 months of age, was significantly lower in TDF group than that in control group (0%-2% vs. 7%-20%) [26, 33,34]. ...
Article
Women at childbearing age and pregnant ladies living in the areas of high or intermediate prevalence of hepatitis B virus (HBV) remain at risk of getting the infection and passing the infections to their offspring via mother-to-child transmission (MTCT) of HBV. HBV infection may affect the mothers by active hepatitis, very occasionally liver cirrhosis and rarely fulminant hepatitis and liver failure. The virus may be transmitted to the babies despite immunoprophylaxis in the setting of very high maternal viral load. Tenofovir disoproxil fumarate (TDF) has been shown to be efficacious to reduce MTCT of HBV, which contributes to the elimination of chronic HBV infection by 2030, the goal set by World Health Organization.
... 5,6 There is now accumulating evidence, particularly from China, that the additional use of tenofovir during the final trimester of pregnancy is a safe and effective method of further reducing MTCT. [7][8][9][10] However, the impact of this strategy at a population level is unknown. ...
Article
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Objective: To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. Methods: We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. Findings: We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Conclusion: Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.
... Neither TDF nor LDT treatment were found to affect long-term growth or bone development in children. This result is consistent with previous studies on TDF in late pregnancy to block mother-tochild transmission of HBV (Greenup et al., 2014;Chen et al., 2015). TDF is reported to affect bone mineral density by influencing phosphate resorption; the main mechanisms of action may be injury of proximal tubular mitochondria, vitamin D insufficiency and specific gene mutation. ...
Article
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Objectives: There are limited data on the efficacy and long-term safety of nucleos(t)ide analogue therapy during the entire pregnancy for chronic hepatitis B women and their children. Methods: This retrospective cohort study included totally 165 patients including 91 patients in telbivudine (LDT) group and 74 patients in tenofovir (TDF) group. The virological response and safety in women were recorded and the physical development and bone mineral density in children was followed up to five years old. Results: The rate of virological breakthrough was 4.24% in all patients, 7.70% in LDT group and 0% in TDF group (P < 0.05). No renal injury or other obstetric adverse event in women was found. As for the physical development or bone density of children, only one child has significant low wight of age Z score (<-2) and no significant low height for age Z score or bone density was found in children, there was no significant difference between the two groups. Conclusions: Nucleos(t)ide analogue therapy including TDF and LDT during entire pregnancy showed no effect on long-term physical development and bone development of children. Additional, TDF during their entire pregnancy showed better long-term antiviral efficacy than LDT with no evidence of renal toxicity.
... Maternal antiviral therapy may be considered for pregnant women with hepatitis B and high viral load > 6-8 log 10 copies/ ml to reduce the risk of intrauterine fetal infection. The viral load at delivery is 3 % with maternal drug treatment and 18 % without treatment [3]. ...
Article
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These statements and recommendations should provide appropriate information about maternal and fetal routes of infection, screening, detection of risk factors, diagnostic procedures, treatment, birth planning and peripartum and postpartum management of maternal hepatitis infection and offer pointers for prenatal counselling and routine clinical care on delivery wards.
... MTCT rates varied according to the provided prophylaxis including (1) timely BD vaccination, (2) timely BD vaccination + tar geted HBIG, and (3) antiviral prophylaxis during pregnancy with TDF + timely BD vaccination + targeted HBIG. Due to the limited availability of these data in Namibia and the rest of SSA, these estimates were taken from clinical trials and observational studies performed elsewhere [18,19,27,[38][39][40][41][42][43][44][45][46][47], and a pooled estimate for each prophylactic measure was calculated. It is worth mentioning that these rates are attributed to the rate of developing CHB infection. ...
Article
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Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model's outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.
... Another primary prevention method is to give prophylactic antiviral treatment to the mother in order to prevent the transmission of hepatitis B to the child in pregnant women with high viremia. It has been shown that tenofovir disoproxil fumarate (TDF) treatment of HBeAg-positive mothers can successfully prevent vertical HBV transmission [12,13]. The AASLD and EASL guidelines suggest antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg-positive pregnant women with an HBV-DNA level > 200,000 IU/mL [14,15]. ...
Article
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Hepatitis B virus (HBV) is the one of most common causes of the hepatocellular carcinoma (HCC), especially in eastern world. The aim of this review is to try to understand the relationship between HBV and HCC and to reveal the role of prevention and treatment of HBV infection in reducing the incidence of HCC. Strategies to prevent HCC due to HBV can be classified into three categories. These are primary, secondary, and tertiary preventions. Hepatitis B vaccine is now in the most vital position in preventing HBV-associated HCC. In patients with chronic hepatitis B infection, suppressing viral load with potent antivirals such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV) prevents the development of HCC and improves prognosis by reducing recurrence after HCC treatments. There is currently no clear consensus on which of these drugs should be preferred. Although data on tenofovir alafenamide (TAF) are scarce, available data with TDF suggest that TAF therapy will also be a strong actor for HCC.
Article
Mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) is a key component of the hepatitis B burden worldwide. Despite its efficacy to prevent HBV transmission, infant vaccination is not enough to control HBV MTCT. Additional efforts are urgently needed to evaluate and scale‐up preventive strategies especially in endemic countries, which are most affected with the epidemic. This review highlights the efficacy and barriers of the currently validated measures for the prevention of HBV MTCT and proposes alternatives adapted to resource‐limited settings to eventually achieve HBV elimination worldwide.
Article
Objective: To observe the efficacy and safety of telbivudine on mother-infant blockade in pregnant women with HBV DNA. Methods: A total of 141 pregnant women between 24 and 28 weeks of gestation and are chronic HBV carriers with HBV DNA≥106 copies/ml were enrolled. 105 in treatment group and 36 in control group. The treatment group was given telbivudine 600 mg/d oral, and the control group did not use antiviral drugs. Hepatitis B immunoglobulin 200 IU intramuscular injection and hepatitis B vaccine 10μg subcutaneous injection were given to the infants in both groups within 12 hours after birth, and 10μg of hepatitis B vaccine was subcutaneously injected when the infants were 1-month and 6-month old. Safety endpoints including HBV DNA quantification, liver function, CK were observed before treatment, 4 weeks after treatment, before delivery, and 24 weeks after delivery. Results: There was no difference in HBV DNA levels between the two groups before treatment and 6 months after delivery (P>0.05). The HBV DNA level in the treatment group was significantly lower than that in the control group before delivery (P<0.05). Between the two groups, Tthe HBV positive rate was statistically different between the two groups (P<0.05), and the difference of serum HBsAg of infants had statistical significance (P<0.05), but Tthe safety of the telbivudine group was not significantly different from that of the control group (P>0.05). Conclusion: The application of telbivudine antiviral therapy in the middle and late stage of pregnancy of HBV high-load pregnant women can significantly reduce the HBV DNA level before delivery, reduce the mother-to-child transmission rate of HBV, and have excellent security. This article is protected by copyright. All rights reserved.
Article
Mother‐to‐child transmission of hepatitis B virus can occur during the intrauterine, antenatal and postnatal periods, with an increased risk of perinatal transmission. Appropriate management of patients who are hepatitis B surface antigen positive during pregnancy can substantially reduce the rates of perinatal transmission. Herein, two pregnant women with chronic hepatitis B are presented; one became pregnant while receiving tenofovir disoproxil fumarate and continued the treatment during pregnancy, the other discontinued tenofovir disoproxil fumarate treatment on her own due to conception, but restarted at 26 weeks of pregnancy. At birth the newborns of both women were vaccinated and immunoglobulin was given, with no perinatal transmission. Whether pregnant women should receive antiviral therapy or immunoprophylaxis still remains controversial. In order to keep the mother's liver stable and to prevent perinatal transmission, it is of paramount importance to manage pregnant women in line with the current information and guidelines.
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Linked Content This article is linked to Wang et al and Pan and Zhang papers. To view these articles, visit https://doi.org/10.1111/apt.15064 and https://doi.org/10.1111/apt.15382.
Chapter
Hepatitis virus infection is often initiated in infancy or childhood. Mother-to-infant transmission is an important transmission route for a large number of patients, with subsequent chronic hepatitis and associated long-term complications including cirrhosis, liver cancer, and mortality. In the past 30 years, measures to prevent mother-to-infant transmission have been investigated extensively especially in hepatitis B virus infection, including screening of pregnant women with HBsAg and/or HBeAg, neonatal immunization with HBV vaccines and hepatitis B immunoglobulin, and postimmunization surveillance for children with breakthrough infection. For up to 10% of infants born to HBsAg-/HBeAg-positive mothers, neonatal immunization may not offer effective protection, and these infants may become chronically infected. Recently, studies have shown that short-term antiviral therapy for HBV-infected pregnant women with a high viral load has effectively prevented mother-to-infant transmission. Mother-to-infant transmission of hepatitis C virus occurs in about 5% of HCV-infected mothers. Screening of pregnant women for HCV is still a controversial issue because no effective preventive measure is currently available. Surveillance of children born to HCV-infected mothers is recommended. Acute HAV and HEV infection in pregnant women is rare, but these infections should be considered when icteric illness occurs in pregnant women. HAV vaccination helps to decrease the susceptible population. Acute HEV infection in pregnant women frequently leads to fulminant hepatic failure, with a high mortality rate for the mother, fetus, and neonates. Most reported cases occurred in an endemic area. Safe drinking water, public health improvement, and newly developed HEV vaccines are effective measures to prevent infection. In conclusion, efforts toward interrupting mother-to-infant transmission of viral hepatitis will effectively improve maternal/fetal/neonatal outcomes, as well as preventing a large population in the world with chronic hepatitis and associated complications.
Article
Background Hepatitis B is a serious global health problem. Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major risk factor in the endemicity of HBV infection. Oral antiviral drugs are recommended to highly viremic mothers to decrease MTCT of HBV. The present network analysis compared the efficacy of available treatments to prevent the MTCT of HBV.Methods The electronic databases of PubMed, Embase, Web of Science, Scopus, and Wanfang data were searched for eligible studies. Pair-wise meta-analysis and Bayesian network analysis were applied to compare the efficacy of antiviral drugs.ResultsSeventy-five studies involving 12,740 pregnant females were eligible for analysis. On pair-wise analysis, lamivudine (OR 0.15, 95% CI 0.09–0.25, I-squared = 0%), telbivudine (OR 0.07, 95% CI 0.05–0.10, I-squared = 0%) and tenofovir (OR 0.07, 95% CI 0.04–0.13, I-squared = 0%) significantly decreased the MTCT rate. Results of multiple comparisons with ranking probability based on Bayesian analysis showed that tenofovir (SUCRA = 96.83%) appeared more effective than the two other drugs.Conclusion In addition to active and passive immunoprophylaxis, lamivudine, telbivudine and tenofovir in highly viremic mothers can further decrease MTCT of HBV. Based on direct and indirect evidence, tenofovir appears to be more effective than the two other drugs in the prevention of HBV MTCT.
Article
Background: The safety and necessity of the hepatitis B immunoglobulin (HBIG) in preventing the mother-to-child transmission of hepatitis B virus (HBV) are still controversial because of its unclear mechanism of action and the inconsistent injection programs used during gestation. Objectives: This study aimed to show the dynamic transportation and distribution of HBIG in the maternal body and to provide evidence for its clinical efficacy in preventing mother-to-child HBV transmission. Study design: Pregnant mice were injected with Cy7-labeled mouse anti-human monoclonal hepatitis B surface antibodies through the tail vein. In vivo imaging technology was used to observe the dynamic transportation and distribution of HBIG in the pregnant mice. Results: HBIG fluorescence signals were higher in the uterus than in the liver, spleen, and kidneys. Fluorescence signals in the uterine region were obviously higher at the third trimester than at early and mid pregnancy. Conclusions: HBIG is gradually deposited in the mouse placenta during pregnancy, with the phenomenon being more significant in the third trimester. This article is protected by copyright. All rights reserved.
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Background: The paucity of Hepatitis B (HBV) DNA measurement in low and middle-income countries hinders the identification of HBV-infected pregnant women at-risk of perinatal transmission. This study evaluates the validity of an algorithm selecting HBeAg-positive women and HBeAg-negative women with alanine aminotransferase (ALT) ≥40 IU/L as predictor of high HBV DNA level. Methods: All women with reactive sample for HBsAg were assessed with SD BIOLINE HBeAg rapid test and HBV DNA quantification was performed. Validities of HBeAg and of the algorithm to identify HBV DNA higher than two thresholds (5.3 and 7.3 Log10 IU/mL) were evaluated. Results: For the 515 positive HBsAg women, median age was 29 years, 92 (17.9%) were HBeAg positive, 47 (9.1%) were HBeAg negative with ALT ≥40 IU/L and 144 (28.0%) had an HBV DNA >5.3 Log10 UI/mL. Sensitivity and specificity of HBeAg were 61.8% and 99.2% for HBV DNA >5.3 Log10 UI/mL and 81.3% and 96.7% for HBV DNA >7.3 Log10 UI/mL. For the algorithm, sensitivity and specificity were 79.2% and 93.3% for HBV DNA level >5.3 Log10 UI/mL and 92.7% and 88.1% for HBV DNA >7.3 Log10 UI/mL. The AUCs for the algorithm (0.92 and 0.94 for HBV DNA >5.3 and 7.3 respectively) were significantly greater (p<0.001) than the AUCs for HBeAg (0.81 and 0.89 for HBV DNA >5.3 and 7.3 respectively). Conclusion: An algorithm using HBeAg and ALT level could be an effective strategy to identify HBV-infected pregnant women at risk of perinatal transmission in countries where HBV DNA quantification is not routinely available.
Article
Background To eliminate mother-to-child transmission (MTCT) of hepatitis B virus (HBV), peripartum antiviral prophylaxis might be required for pregnant women infected with HBV who have a high risk of MTCT despite infant immunoprophylaxis. We aimed to determine the efficacy and safety of peripartum antiviral prophylaxis to inform the 2020 WHO guidelines. Methods In this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, CENTRAL, CNKI, and Wanfang for randomised controlled trials and non-randomised studies of peripartum antiviral prophylaxis versus placebo or no prophylaxis, with no language restriction, published from database inception until March 28, 2019. We used search terms covering HBV, antiviral therapy, and pregnancy. We included studies that enrolled pregnant women with chronic infection with HBV who received antiviral prophylaxis anytime during pregnancy; that included any of the following antivirals: adefovir, emtricitabine, entecavir, lamivudine, telbivudine, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate; and that reported the following outcomes: MTCT, indicated by infant HBsAg positivity or HBV DNA positivity, or both, at age 6–12 months, and any infant or maternal adverse events. Two reviewers independently extracted data. Our primary endpoint was MTCT based on infant HBsAg positivity. We assessed pooled odds ratios (ORs) of the efficacy of peripartum antiviral prophylaxis to reduce the risk of MTCT. We assessed safety of prophylaxis by pooling risk differences. The protocol for the systematic review was pre-registered in PROSPERO, CRD42019134614. Findings Of 7463 articles identified, 595 articles were eligible for full-text review and 129 studies (in 157 articles) were included. The following antivirals were assessed in the meta-analysis: tenofovir disoproxil fumarate 300 mg (19 studies, with 1092 mothers and 1072 infants), lamivudine 100–150 mg (40 studies, with 2080 mothers and 2007 infants), and telbivudine 600 mg (83 studies, with 6036 mothers and 5971 infants). The pooled ORs for randomised controlled trials were similar, at 0·10 (95% CI 0·03–0·35) for tenofovir disoproxil fumarate, 0·16 (0·10–0·26) for lamivudine, and 0·14 (0·09–0·21) for telbivudine. The pooled ORs in non-randomised studies were 0·17 (0·10–0·29) for tenofovir disoproxil fumarate, 0·17 (0·12–0·24) for lamivudine, and 0·09 (0·06–0·12) for telbivudine. We found no increased risk of any infant or maternal safety outcomes after peripartum antiviral prophylaxis. Interpretation Peripartum antiviral prophylaxis is highly effective at reducing the risk of HBV MTCT. Our findings support the 2020 WHO recommendation of administering antivirals during pregnancy, specifically tenofovir disoproxil fumarate, for the prevention of HBV MTCT. Funding World Health Organization.
Chapter
Before the introduction of hepatitis B virus (HBV) vaccination, mother‐to‐baby transmission was a key route of HBV acquisition, particularly in Asian countries. For HBV‐infected mothers, coadministration of hepatitis B immunoglobulin with birth dose vaccine can offer additional protection to the newborn to prevent perinatal transmission. Pregnancy is a special stage of life when cell‐mediated immunity is suppressed to tolerate paternally derived fetal antigens, while the immunology changes are reversed back to normal postpartum. As a result, elevation of alanine aminotransferase may develop in the postpartum period in HBV carrier mothers. The use of antiviral therapy (lamivudine, telbivudine, tenofovir disoproxil fumarate) is safe for both the mother and the fetus. Based on reports from observational studies, there was no increase in congenital malformation and prematurity for infants or increase in postpartum hemorrhage, cesarean section rate or elevated creatine kinase rate for mothers who received antiviral therapy.
Article
Hepatitis B virus (HBV) is a global health problem. Vertical transmission of HBV from HBV surface antigen (HBsAg)‐positive mothers to their infants is the most common cause of HBV infection worldwide. The use of passive–active immunoprophylaxis is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to mothers with high viremia. Thus, it is recommended that pregnant women with HBV‐DNA level >200,000 IU/mL receive nucleos(t)ide analogue (NA) treatment [i.e., tenofovir disoproxil fumarate (TDF), lamivudine (LAM), or telbivudine (LdT)] during third trimester to prevent infant immunoprophylaxis failure. TDF is recommended as first‐line therapy based on available data on efficacy, safety and resistance profile. However, maternal immunologic reconstitution following parturition can increase immune‐mediated flares to viral antigens, that is potentially exacerbated following TDF withdrawal. In this article, we review available data on the efficacy and safety of TDF administration to prevent HBV mother‐to‐child transmission. We also discuss changes in maternal viral markers [i.e., HBV‐DNA, HBV e antigen (HBeAg) and HBsAg] and alanine aminotransferase (ALT) during follow‐up postpartum in mothers received NA to prevent HBV vertical transmission.
Article
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Background: Data evaluating the risk of proximal tubular dysfunction in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission (PMTCT) of HBV are scarce. Objectives: To assess the risk of proximal tubulopathy in pregnant women receiving tenofovir disoproxil fumarate for PMTCT of HBV. Patients and methods: We used urine samples collected from HBV monoinfected pregnant women who participated in a Phase III, multicentre, randomized, double-blind, placebo-controlled clinical trial assessing a tenofovir disoproxil fumarate short course from 28 weeks gestational age (28-wk-GA) to 2 months post-partum (2-months-PP) for PMTCT of HBV in Thailand. Markers of tubular dysfunction, including retinol binding protein, kidney injury molecule-1, α1-microglobuin and β2-microglobulin, were assayed at 28- and 32-wk-GA and 2-months-PP visits. Proximal tubulopathy was defined as the presence of ≥2 of the following: tubular proteinuria, euglycaemic glycosuria and increased urinary phosphate. Results: A total of 291 women participated in the study. No kidney-related adverse events were severe, and none led to tenofovir disoproxil fumarate discontinuation. At 2-months-PP, 3 of the 120 (3%) evaluated women in the tenofovir disoproxil fumarate group experienced proximal tubulopathy versus 3 of 125 (2%) in the placebo group (P = 1.00). None of the six women met the criteria for proximal tubulopathy at 12-months-PP but proteinuria persisted in three of them. No growth abnormalities were found at 1 year of age in infants born to mothers with proximal tubulopathy at 2-months-PP. Conclusions: In these HBV-infected pregnant and breastfeeding women, tenofovir disoproxil fumarate administered from 28-wk-GA to 2-months-PP was not associated with a higher risk of proximal tubulopathy.
Chapter
Since 1982, safe and effective hepatitis B virus (HBV) vaccines have been commercially available first derived from plasma of HBV-infected persons and later from yeast cells using recombinant DNA technology. Hepatitis B vaccines have an overall efficacy of 80–100% and provide virtually complete protection against acute and chronic hepatitis B infection among persons who complete the three-dose vaccination series; a two-dose vaccine is now available. Despite decrease or loss of serologic evidence of a protective immune response over time, immune protection from hepatitis B vaccination lasts for more than 30 years. New hepatitis B vaccines provide new options for achieving seroprotective levels of immunity among populations (e.g., HIV-seropositive patients, the elderly) typically hyporesponsive to vaccination and to decrease the number of doses required to achieve an effective immune response. The greatest health impact is achieved through childhood vaccination beginning at birth, as children infected with HBV at birth or early childhood are at greatest risk for developing chronic HBV infection and HBV-related liver disease in later life. Globally, universal hepatitis B vaccination is recommended for all infants beginning preferably within 24 h of birth, full immunization of infants by routine immunization programs in the first 3 years of life, and catch-up vaccination of unimmunized older children and adults. Evidence is growing that antiviral prophylaxis given in the last trimester of pregnancy to women with a high viral load of HBV can lower the risk for perinatal transmission of HBV among newborns who receive a timely dose of hepatitis B vaccine. As of 2019, global coverage of infant HepB three-dose immunization was 85% with 189 countries (>95%) routinely vaccinating infants against HBV infection approaching the HBV “elimination” goal of 90% coverage. As of 2016, the 43% global coverage of hepatitis B birth dose vaccination falls short of this 90% coverage goal. Rates of HBV incidence, prevalence, and liver cancer fall dramatically among vaccinated cohorts. As a result, hepatitis B vaccination is one of the most cost-effective public health interventions available, yielding a cost per life saved of $4–$36 in low-income countries. The WHO has developed a framework for global action, with the goal of eliminating HBV and hepatitis C virus (HCV) as public health threats by 2030. Hepatitis B elimination can be achieved when countries implement comprehensive hepatitis B virus immunization programs including hepatitis B vaccine in national childhood immunization schedules, vaccinating newborns for hepatitis B, and providing catch-up vaccination for children or adolescents, and adults.
Article
Objective The physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy. Design Infants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants’ physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age. Results Of 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social–emotional, and adaptive behaviour measurements) were all comparable between the groups. Conclusion Infants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission. Trial registration number NCT01488526 .
Article
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the main cause of chronic hepatitis B. The prevention of MTCT plays a critical role in control chronic hepatitis B. The main purpose of the present clinical guidelines is to aid healthcare providers in managing pregnant women with positive HBsAg and in preventing MTCT of HBV. We recommend: (1) all pregnant women require prenatal screen for hepatitis B serological markers; (2) newborn infants of mothers with negative hepatitis B surface (HBsAg) require administration of hepatitis B vaccine on a 0, 1, and 6 month-schedule; (3) newborn infants of mothers with positive HBsAg need hepatitis B immunoglobulin (HBIG) and birth dose vaccine within 12 hours (the sooner the better) after birth, followed by injection of the second and third dose of hepatitis B vaccine at the age of one and six months respectively; (4) in preterm neonates or neonates with poor health conditions born to HBsAg-positive mothers, the immunoprophylaxis measures should be appropriately taken; (5) to further reduce MTCT of HBV, pregnant women with HBV DNA levels >2 × 105 IU/mL or positive hepatitis B e antigen may receive oral antivirals, starting from 28 to 32 weeks of gestation and discontinuing the drug on the delivery day; (6) cesarean section is not recommended to reduce MTCT of HBV; (7) breastfeeding is recommended in infants of HBsAg-positive mothers, regardless of maternally positive hepatitis B e antigen, maternal nipple injury or bleeding, oral mucosal injury in neonates or infants; (8) breastfeeding is recommended in infants born to HBsAg-positive mothers who require continuation of antiviral therapy after delivery, and the infants should be followed up to observe whether adverse effects develop; and (9) the infants born to HBsAg-positive mothers should be tested for hepatitis B serological markers at the age of 7–12 months, and those who are negative for HBsAg and anti-HBs should receive three doses of hepatitis B vaccine on the 0, 1, and 6 month-schedule as soon as possible.
Article
Background Tenofovir disoproxil fumarate (TDF) is recommended for the prevention of perinatal transmission of the hepatitis B virus (HBV). This study aimed to systematically assess the efficacy and safety of TDF in pregnant women with chronic HBV and their infants. Material and methods Database searches were performed to identify studies blocking the mother-to-child transmission of the hepatitis B virus with tenofovir. The search included pregnant women with chronic HBV infection administered with TDF compared to the no treatment controls, and data from individual studies were pooled using RevMan v5.3 for meta-analysis. Results Seven studies with a total of 911 patients met the inclusion criteria: 433 patients in the TDF group and 478 patients in the non-TDF group. The HBV mother-to-child transmission rate in the tenofovir group was effectively reduced compared to the control group (RR: 0.18, 95% CI: 0.08-0.40). HBV-DNA positivity was also significantly low in infants from TDF group (RR: 0.17, 95% CI: 0.10-0.30) and the TDF treatment resulted in significantly higher anti-HBs production (RR: 1.11, 95% CI: 1.04-1.18). Similarly, maternal HBV-DNA was suppression was significantly high in the TDF group (RR: 34.16, 95% CI: 16.40-71.13). Women treated with TDF and their infants did not result in serious adverse events that are statistically different as compared to the women who did not receive any treatment. Conclusion Treatment of HBV infected pregnant women with TDF can effectively and safely prevent the perinatal transmission of chronic hepatitis B.
Article
The management of viral hepatitis in the setting of pregnancy requires special consideration. There are five liver-specific viruses (hepatitis A, B, C, D, E), each with unique epidemiology, tendency to chronicity, risk of liver complications and response to antiviral therapies. In the setting of pregnancy, the liver health of the mother, the influence of pregnancy on the clinical course of the viral infection and the effect of the virus or liver disease on the developing infant must be considered. Although all hepatitis viruses can harm the mother and the child, the greatest risk to maternal health and subsequently the fetus is seen with acute hepatitis A virus or hepatitis E virus infection during pregnancy. By contrast, the primary risks for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus are related to the severity of the underlying liver disease in the mother and the risk of mother-to-child transmission (MTCT) for HBV and HCV. The prevention of MTCT is key to reducing the global burden of chronic viral hepatitis, and prevention strategies must take into consideration local health-care and socioeconomic challenges. This Review presents the epidemiology of acute and chronic viral hepatitis infection in pregnancy, the effect of pregnancy on the course of viral infection and, conversely, the influence of the viral infection on maternal and infant outcomes, including MTCT.
Article
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 antivirals needs more evidence, which can be achieved from the real-world data analysis.
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p>Hepatitis adalah peradangan pada sel-sel hati, yang bisa disebabkan oleh infeksi (virus, bakteri, parasit), obat-obatan (termasuk obat tradisional), konsumsi alkohol, lemak yang berlebih dan penyakit autoimun . Indonesia merupakan salah satu negara di Asia tenggara yang menduduki salah satu negara dengan endemis hepatitis. Metode dalam penulisan artikel ini adalah studi literatur ( literature review ).Wanita hamil dengan infeksi virus hepatitis B akut memiliki jalur yang tidak jauh berbeda dengan populasi orang dewasa, tetapi risiko penularan Hepatitis B ke neonatus meningkat pada masa kehamilan, saat infeksi akut terjadi.Infeksi Hepatitis B kronis biasanya dapat meningkat setelah melahirkan.Risiko penularan perinatal tertinggi pada wanita dengan tingkat viraemia tinggi; hal ini menjelaskan kegagalan imunoprofilaksis.Penularan terbesar terjadi kepada bayi yang dilahirkan oleh ibu dengan positif hepatitis B. Penularan terhadap bayi terjadi ketika masih dalam kandungan, saat melahirkan dan setelah persalinan. Pencegahan hepatitis B dapat dilakukan dengan melakukan skrining pada saat pemeriksaan kehamilan pertama.Untuk menurunkan angka transmisi penularan hepatitis B, dianjurkan ibu hamil dengan positif hepatitis B melakukan persalinan dengan metode sectio caesaria elektif.</p
Article
Background: Tenofovir disoproxil fumarate (TDF) is recommended for the prevention of perinatal transmission of the hepatitis B virus (HBV). This study aimed to systematically assess the efficacy and safety of TDF in pregnant women with chronic HBV and their infants. Material and methods: Database searches were performed to identify studies blocking the mother-to-child transmission of the hepatitis B virus with tenofovir. The search included pregnant women with chronic HBV infection administered with TDF compared to the no treatment controls, and data from individual studies were pooled using RevMan v5.3 for meta-analysis. Results: Seven studies with a total of 911 patients met the inclusion criteria: 433 patients in the TDF group and 478 patients in the non-TDF group. The HBV mother-to-child transmission rate in the tenofovir group was effectively reduced compared to the control group (RR: 0.18, 95% CI: 0.08-0.40). HBV-DNA positivity was also significantly low in infants from TDF group (RR: 0.17, 95% CI: 0.10-0.30) and the TDF treatment resulted in significantly higher anti-HBs production (RR: 1.11, 95% CI: 1.04-1.18). Similarly, maternal HBV-DNA was suppression was significantly high in the TDF group (RR: 34.16, 95% CI: 16.40-71.13). Women treated with TDF and their infants did not result in serious adverse events that are statistically different as compared to the women who did not receive any treatment. Conclusion: Treatment of HBV infected pregnant women with TDF can effectively and safely prevent the perinatal transmission of chronic hepatitis B.
Article
Objective Tenofovir disoproxil fumarate (TDF) use compared with telbivudine (LdT) use throughout pregnancy has not been adequately investigated. To compare the efficacy and safety of TDF and LdT for the prevention of mother-to-child transmission (MTCT) of hepatitis B from highly viremic mothers throughout pregnancy in real-world settings. Study design This was a single-center, retrospective cohort study. From January 1, 2013, to December 31, 2018, we retrospectively enrolled 602 mothers with chronic hepatitis B (CHB) who received antiviral treatment throughout pregnancy at Beijing Ditan Hospital. A total of 562 mothers met the inclusion criteria, with 167 in the TDF group and 395 in the LdT group. Mothers and infants were followed for 28 weeks postpartum. The primary endpoint was the MTCT rate of HBV. The secondary endpoints were the safety profiles in mothers and infants. Results The MTCT rates were 0% in both the TDF and LdT groups. The rates of neonatal congenital abnormalities were similar between the TDF and LdT groups (1.2% vs. 1.8%, P = 0.896). There were no significant differences in perinatal complications between the two groups (all P > 0.05). There were also no significant differences in gestational age or infant height, weight, Apgar score. The level of HBV DNA at 28 weeks postpartum was an independent risk factor for postpartum alanine aminotransferase (ALT) flares (OR = 2.348, 95% CI: 1.100-5.016, P = 0.027). Conclusion TDF and LdT treatments throughout pregnancy in mothers with CHB were equally effective in preventing MTCT and safe.
Article
The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune-tolerant phase with HBV DNA levels >6 log10 IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum-elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% [27/53] vs 58.3% [14/24] vs 40.7% [11/27], respectively; P = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.
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Objective Reducing mother-to-child transmission(MTCT)of hepatitis B virus(HBV) is one of the key ways to eliminate hepatitis B. Although studies have demonstrated the effectiveness of oral nucleos(t)ide analogs(NAs),drug’s comparisons are lacking. The network meta-analysis aims to comprehensively compare and summarize the efficacy and safety of the three drugs (Lamivudine(LAM), Telbivudine(TBV) and Tenofovir(TDF)), providing a basis for drug selection. Methods A comprehensive retrieval of data was conducted from PubMed (Medline), Web of Science, the Cochrane Library, EMBASE, CNKI and SinoMed through to December 2019. We performed pair-wise meta-analysis and Bayesian network meta-analysis to compare the efficacy and safety of NAs. Results A total of 35 studies whith involving a total of 6,109 pregnant women with HBV infenction were selected. All three drugs can effectively block MTCT and improve HBV DNA suppression (p < 0.05). No significant differences were found in the occurrence of adverse events in mothers and infants.The results of the network meta analysis showed that the possibility of TBV and TDF being the best drug was 50% and 46%, the possibility of TBV and TDF being the second is the same-45%, the possibility of LAM being the worst drug is 85%. Conclusion LAM, TBV and TDF are effective in preventing MTCT of HBV in women with chronic HBV infection with high viral load. Using them does not seem to increase the probability of adverse events in pregnant women and infants. It cannot be ignored that TDF and TBV appear to show better blocking effects in clinical practice.
Article
Mother‐to‐child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicine for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester has not been compared rigorously. Therefore, we carried out a prospective multicenter cohort study of chronic hepatitis B in mothers with HBV DNA > 106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow‐up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titer at the baseline correlated with viral DNA decrease (P= 0.015). With intention to treat analysis, MTCT rates in the LdT, TDF and NTxgroup were 4.41%, 2.42%, and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titer; 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg >4 and >5 log10 IU/mL, respectively. No serious side‐effects were reported ineither mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg >4 log10IU/mL. This article is protected by copyright. All rights reserved.
Article
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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.
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Objective: To investigate the proportion and type of fetal anomalies that are associated with polyhydramnios and to examine whether in cases with idiopathic polyhydramnios during the course of pregnancy and fetal anomalies only diagnosed after birth, antenatal characteristics differ. Methods: This was a retrospective study involving all pregnancies with polyhydramnios defined by a deepest pool of amniotic fluid ≥8 cm and a detailed ultrasound examination, a 75 g glucose tolerance test and a TORCH serology. Results: Between 2004 and 2010, 272 pregnancies fulfilled the inclusion criteria. In 89 (32.7%) and 65 (23.9%) cases, there was a fetal anomaly or diabetes. In 118 (43.4%) pregnancies, polyhydramnios was classified as idiopathic. In 11 (9.3%) of the 118 fetuses, an anomaly was found after birth, mainly gastrointestinal atresia. In these cases, median deepest pool of amniotic fluid was 9.6 cm, and median estimated fetal weight was at the 69th centile, whereas in cases without anomalies diagnosed after birth, median deepest pool was 9.0 cm and median estimated fetal weight at the 90th centile (Mann-Whitney U test: deepest pool p = 0.116, and estimated fetal weight centile p = 0.377). There was also no difference in the maternal and gestational age distribution of these cases (Mann-Whitney U test: maternal age p = 0.293, and gestational age p = 0.499). Conclusion: In about 40% of pregnancies, polyhydramnios remains unexplained during the course of pregnancy. In 10% of these cases, an anomaly will only be found after birth. In this group, antenatal characteristics such as amniotic fluid volume, estimated fetal weight or gestational and maternal age at the time of diagnosis do not help to detect these anomalies before birth.
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Preterm birth is the second largest direct cause of child deaths in children younger than 5 years. Yet, data regarding preterm birth (<37 completed weeks of gestation) are not routinely collected by UN agencies, and no systematic country estimates nor time trend analyses have been done. We report worldwide, regional, and national estimates of preterm birth rates for 184 countries in 2010 with time trends for selected countries, and provide a quantitative assessment of the uncertainty surrounding these estimates. METHODS: We assessed various data sources according to prespecified inclusion criteria. National Registries (563 datapoints, 51 countries), Reproductive Health Surveys (13 datapoints, eight countries), and studies identified through systematic searches and unpublished data (162 datapoints, 40 countries) were included. 55 countries submitted additional data during WHO's country consultation process. For 13 countries with adequate quality and quantity of data, we estimated preterm birth rates using country-level loess regression for 2010. For 171 countries, two regional multilevel statistical models were developed to estimate preterm birth rates for 2010. We estimated time trends from 1990 to 2010 for 65 countries with reliable time trend data and more than 10,000 livebirths per year. We calculated uncertainty ranges for all countries. FINDINGS: In 2010, an estimated 14·9 million babies (uncertainty range 12·3-18·1 million) were born preterm, 11·1% of all livebirths worldwide, ranging from about 5% in several European countries to 18% in some African countries. More than 60% of preterm babies were born in south Asia and sub-Saharan Africa, where 52% of the global livebirths occur. Preterm birth also affects rich countries, for example, USA has high rates and is one of the ten countries with the highest numbers of preterm births. Of the 65 countries with estimated time trends, only three (Croatia, Ecuador, and Estonia), had reduced preterm birth rates 1990-2010. INTERPRETATION: The burden of preterm birth is substantial and is increasing in those regions with reliable data. Improved recording of all pregnancy outcomes and standard application of preterm definitions is important. We recommend the addition of a data-quality indicator of the per cent of all live preterm births that are under 28 weeks' gestation. Distinguishing preterm births that are spontaneous from those that are provider-initiated is important to monitor trends associated with increased caesarean sections. Rapid scale up of basic interventions could accelerate progress towards Millennium Development Goal 4 for child survival and beyond. FUNDING: Bill & Melinda Gates Foundation through grants to Child Health Epidemiology Reference Group (CHERG) and Save the Children's Saving Newborn Lives programme; March of Dimes; the Partnership for Maternal Newborn and Childe Health; and WHO, Department of Reproductive Health and Research.
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Background: Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Methods and findings: Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens. Conclusions: Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children. Trial registration: www.controlled-trials.com ISRCTN13968779
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Despite appropriate immunoprophylaxis, up to 10 % of infants born to highly viremic hepatitis B virus (HBV-DNA ≥ 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated. To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers. Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. Eleven Asian mothers received TDF at the median gestational age of 29 (28-32) weeks and the median duration of TDF use before delivery was 10 (7-12) weeks. A significant reduction in serum HBV-DNA was achieved at delivery compared with baseline (mean 5.25 ± 1.79 vs. 8.87 ± 0.45 log(10) copies/mL, respectively; p < 0.01). Three had serum ALT levels more than 1.5 times the upper limit of normal and two of these normalized before delivery. The 11 infants were born with no obstetric complication or birth defects. Five infants were breastfed. All infants were hepatitis B surface antigen negative 28-36 weeks after birth. Our preliminary data suggest that TDF use in the third trimester is safe, and effectively prevents VT of HBV from high viremic HBeAg-positive mothers.
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To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure. Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17 vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02). TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.
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To determine the rate of perinatal hepatitis B virus (HBV) transmission in an Australian setting and to identify maternal virological factors associated with highest risk of transmission. A prospective, observational study of perinatal transmission of HBV. Participants were pregnant women attending Sydney South West Area Health Service antenatal clinics who tested positive for hepatitis B surface antigen (HBsAg), and their babies. All babies were routinely offered hepatitis B immunoglobulin (HBIG) and HBV vaccination. Babies positive for HBsAg at 9-month follow-up underwent further virological testing, including HBV DNA sequencing. The study was conducted between August 2002 and May 2008. HBV DNA levels and demographic characteristics of HBsAg-positive pregnant women; proportion of their infants with active HBV infection at 9-month follow-up; maternal characteristics affecting transmission rate; HBV DNA sequencing of infected infants and their mothers. Of 313 HBsAg-positive pregnant women, 213 (68%) were HBV DNA-positive and 92 (29%) were positive for hepatitis B "e" antigen (HBeAg); 138 babies born to HBV DNA-positive mothers were tested for HBV infection (HBsAg positivity) at about 9 months of age. Four cases of transmission were identified. All four mothers had very high HBV DNA levels (> 10(8) copies/mL) and were HBeAg-positive. Three of the four infants were infected with wild-type HBV strains, with identical maternal/infant isolates. The fourth mother-infant pair had an S gene variant, HBV D144E, which has been previously reported in association with vaccine/HBIG escape. (Unfortunately, HBIG was inadvertently omitted from the immunisation schedule of this infant.) Transmission rates were 4/138 (3%) from HBV DNA-positive mothers overall, 4/61 (7%) from HBeAg-positive mothers, and 4/47 (9%) from mothers with very high HBV DNA levels. No transmission was seen in 91 babies of mothers with HBV DNA levels < 10(8) copies/mL. In this cohort, HBV perinatal transmission was restricted to HBeAg-positive mothers with very high viral loads.
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To investigate the effect of hepatitis B virus (HBV) specific immunoglobin (HBIG) and lamivudine on HBV intrauterine transmission in HBsAg positive pregnant women. Each subject in the HBIG group (56 cases) was given 200 IU HBIG intramuscularly (im.) every 4 weeks from 28-week (wk) of gestation, while each subject in the lamivudine group (43 cases) received 100 mg lamivudine orally (po.) every day from 28-wk of gestation until the 30(th) day after labor. Subjects in the control group (52 cases) received no specific treatment. Blood specimens were tested for HBsAg, HBeAg, and HBV-DNA in all maternities at 28-wk of gestation, before delivery, and in their newborns 24 hours before the administration of immune prophylaxis. Reductions of HBV DNA in both treatments were significant (P<0.05). The rate of neonatal intrauterine HBV infection was significantly lower in HBIG group (16.1 %) and lamivudine group (16.3 %) compared with control group (32.7 %) (P<0.05), but there was no significant difference between HBIG group and lamivudine group (P>0.05). No side effects were found in all the pregnant women or their newborns. The risk of HBV intrauterine infection can be effectively reduced by administration of HBIG or Lamivudine in the 3(rd) trimester of HBsAg positive pregnant women.
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To evaluate the effects of hepatitis B vaccine and immunoglobulin in newborn infants of mothers positive for hepatitis B surface antigen. Systematic review and meta-analysis of randomised clinical trials. Electronic databases and hand searches. Randomised clinical trials were assessed for methodological quality. Meta-analysis was undertaken on three outcomes: the relative risks of hepatitis B occurrence, antibody levels to hepatitis B surface antigen, and adverse events. 29 randomised clinical trials were identified, five of which were considered high quality. Only three trials reported inclusion of mothers negative for hepatitis B e antigen. Compared with placebo or no intervention, vaccination reduced the occurrence of hepatitis B (relative risk 0.28, 95% confidence interval 0.20 to 0.40; four trials). No significant difference in hepatitis B occurrence was found between recombinant vaccine and plasma derived vaccine (1.00, 0.71 to 1.42; four trials) and between high dose versus low dose vaccine (plasma derived vaccine 0.97, 0.55 to 1.68, three trials; recombinant vaccine 0.78, 0.31 to 1.94, one trial). Compared with placebo or no intervention, hepatitis B immunoglobulin or the combination of plasma derived vaccine and hepatitis B immunoglobulin reduced hepatitis B occurrence (immunoglobulin 0.50, 0.41 to 0.60, one trial; vaccine and immunoglobulin 0.08, 0.03 to 0.17, three trials). Compared with vaccine alone, vaccine plus hepatitis B immunoglobulin reduced hepatitis B occurrence (0.54, 0.41 to 0.73; 10 trials). Hepatitis B vaccine and hepatitis B immunoglobulin seem safe, but few trials reported adverse events. Hepatitis B vaccine, hepatitis B immunoglobulin, and vaccine plus immunoglobulin prevent hepatitis B occurrence in newborn infants of mothers positive for hepatitis B surface antigen.
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Background: Severe hyperlactataemia and lactic acidosis are rare serious complications of antiretroviral therapy (ART). Methods: Lactic acidosis was defined as pH < 7.35, bicarbonate < 20 mmol/l and raised lactate; hyperlactataemia as two consecutive lactates > 5 mmol/l. The case-control study of 110 cases and 220 controls(two randomly selected from treated patients by centre and calendar year) from centres in 10 countries included 40 (36.4%) female cases and 40 female controls (18.2%) (P < 0.001). Median age was 42.4 years [interquartile range (IQR, 36.0-52.5] for cases and 40 (IQR, 35.0-47.1) for controls (P = 0.013). More cases were nonwhite (41.9%) than controls (31.2%) (P = 0.032). Cases had a shorter duration of exposure to dideoxynucleosides. Results: After adjusting for age, gender and current CD4 cell count, hyperlactataemia/lactic acidosis remained associated with exposure to didanosine in every category of exposure duration but was most strongly associated with exposure < 12 months. In a separate multivariable model, apart from exposure to stavudine, didanosine, or even more strongly both, age above 40 years [odds ratio (OR), 2.6; 95% confidence interval (CI), 1.08-6.29], female gender (OR, 5.97; 95% CI, 1.92-18.5) and advanced immunosuppression were independent associations (CD4 cell count 200-349, 100-199 and < 100 cells/mul: OR, 3.89, 7.58 and 8.11, respectively). Interpretation: Hyperlactataemia/lactic acidosis was associated with exposure to dideoxynucleosides, female gender, advanced immunosuppression and possibly ethnicity. This has important consequences for choice of ART in resource-limited settings. The association with shorter duration of exposure may support the hypothesis of susceptibility in a small proportion of patients.
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Chronic hepatitis B virus (HBV) infection in pregnancy presents a unique and important challenge. Over 50% of chronic HBV carriers in endemic areas acquire infection vertically from their mothers. More importantly, over 90% of perinatally acquired infections progress to chronic HBV infection. Thus, management of chronic HBV during pregnancy and strategies to prevent mother-to-child transmission is an important step in eradicating or reducing the global burden of chronic hepatitis B. In addition, chronic HBV infection in pregnancy presents a unique clinical challenge because of the complex relationship between the physiological changes of pregnancy and the pathophysiological response to HBV. This review will present the current knowledge and a practical approach to management of HBV in pregnancy.
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Antepartum anti-viral therapy (AVT) is often administered to prevent perinatal transmission of hepatitis B virus (HBV) infection. Little is known about the effect of AVT on post-partum flare rates and severity. To examine whether extending AVT beyond birth influences the post-partum course. One hundred and one pregnancies in 91 women with HBV DNA levels ≥log 7 IU/mL were included. AVT (initially lamivudine, later tenofovir disoproxil fumarate) was commenced from 32 weeks gestation and stopped soon after birth and at 12 weeks post-partum. Outcomes according to post-partum treatment duration were examined: Group 1 = AVT ≤4 weeks (n = 44), Group 2 = AVT >4 weeks (n = 43), Group 3 = no AVT (n = 14). The majority of women were HBeAg+ (97%), median age 29 years, baseline HBV DNA log 8.0 IU/mL and follow-up 48 weeks post-partum. Post-partum treatment duration was 2 weeks for Group 1 and 12 weeks for Group 2, P < 0.01. Flare rates were not significantly different: Group 1 = 22/44 (50%), Group 2 = 17/43 (40%) and Group 3 = 4/14 (29%), P = 0.32. Onset of flare was similar at 8/10/9 weeks post-partum for Groups 1/2/3 respectively, P = 0.34. The majority of flares spontaneously resolved. HBeAg seroconversion (n = 1/5/1 in Groups 1/2/3, P = 0.27) was not associated with treatment duration or the occurrence of a post-partum flare. Post-partum flares are common and usually arise early after delivery. They are often mild in severity and most spontaneously resolve. Extending anti-viral therapy does not protect against post-partum flares or affect HBeAg seroconversion rates.
Article
This study sought to assess the antiviral efficacy of lamivudine (LMV) administered during third trimester to reduce maternal viraemia and to identify the emergence of LMV resistance. A prospective observational analysis was performed on 26 mothers with high viral load (>10(7) IU/mL). Twenty-one women received LMV (treated group) for an average of 53 days (range 22-88 days), and the remaining five formed the untreated control group. Serum samples from two time points were used to measure HBV DNA levels and antiviral drug resistance. The LMV-treated women achieved a median HBV DNA reduction of 2.6-log10 IU/mL. Although end-of-treatment (EOT) HBV DNA in four (18%) LMV-treated women remained at >10(7) IU/mL (±0.5 log IU/mL), no mother-to-baby transmission was observed. In contrast, a baby from the untreated mother was HBsAg positive at 9 months postpartum. Four technologies were used for drug resistance testing. Only ultra-deep pyrosequencing (UDPS) was sufficiently sensitive to detect minor viral variants down to <1%. UDPS showed that LMV therapy resulted in increased viral quasispecies diversity and positive selection of HBV variants with reverse transcriptase amino acid substitutions at sites associated with primary LMV resistance (rtM204I/V and rtA181T) in four (19%) women. These viral variants were detected mostly at low frequencies (0.63-5.92%) at EOT, but one LMV-treated mother had an rtA181T variant that increased from 2.2% pretherapy to 25.59% at EOT. This mother was also infected with the vaccine escape variant (sG145R), which was inhibited by LMV treatment. LMV therapy during late pregnancy only reduced maternal viraemia moderately, and drug-resistant viral variants emerged.
Article
Aim: The objective of this study is to compare head circumferences (HCs) measured on the day of delivery and on the third day after delivery. Method: A total of 499 children born in the maternity department were recruited for the study. HC was measured in centimeters immediately after birth and on the third day after delivery. Results: There are statistically significant differences between HC at the time of birth and on the third day. Presentation and method of delivery were significantly associated with differences in HC. For presentation, we found that breech newborns more commonly have smaller HC on day 3 measurements (P = .001). For method of delivery, we found that cesarean sections also were more commonly associated with having smaller HC on day 3 measurement (P = .02). Conclusion: Measuring HC on the third day is more clinically valuable because much of the effects of molding and birth injuries will have subsided in most newborns.
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Hepatitis B infection is best controlled by prevention rather than treatment, as chronic infection is usual once infected at a young age. Infant immune-prophylaxis is highly efficacious, although in the setting of high maternal viral load, breakthrough infection still occurs in almost 10 % of babies. Ante partum antiviral therapy for the purpose of preventing mother to child transmission in this group is important to consider. This article provides an up-to-date account of the available evidence of the safety and efficacy of ante partum antiviral therapy options and a management plan is proposed. Mothers with HBV infection and high viral load should have the opportunity to consider this evidence. Post-partum HBV flares are common but usually mild. It is unclear whether post partum flares are best ignored till they settle or if they represent an opportunity for intervention to increase the chance of HBV clearance.
Article
Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.
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Hepatitis B infection remains the most common form of chronic hepatitis. Mother to child transmission occurs despite immunoprophylaxis with vaccination and immunoglobulin. In utero infection is suggested to account for most of the cases with immunoprophylaxis failure. Infants who suffer from hepatitis B infection at birth have a higher risk of becoming chronic carriers and may develop liver cirrhosis or hepatocellular carcinoma in the future. Infected germ cells, transplacental infection, invasive prenatal diagnostic tests and various perinatal factors are possible factors leading to in utero infection and subsequent immunoprophylaxis failure. Hepatitis B e antigen positive status and high viral load increase the risk of immunoprophylaxis failure. Recent evidence shows promising results regarding the use of antiviral treatment in late gestation to suppress viral load, so as to decrease the risk of vertical transmission. This review discusses the possible mechanisms of in utero infection and the use of antiviral treatment during pregnancy.
Article
This study aimed to determine whether administration of lamivudine to pregnant women with chronic hepatitis B in the third trimester is a cost-effective strategy in preventing perinatal transmission. We developed a decision analysis model to compare the cost-effectiveness of 2 management strategies for chronic hepatitis B in pregnancy: (1) expectant management or (2) lamivudine administration in the third trimester. We assumed that lamivudine reduced perinatal transmission by 62%. Our Markov model demonstrated that lamivudine administration is the dominant strategy. For every 1000 infected pregnant women treated with lamivudine, $337,000 is saved and 314 quality-adjusted life-years are gained. For every 1000 pregnancies with maternal hepatitis B, lamivudine prevents 21 cases of hepatocellular carcinoma and 5 liver transplants in the offspring. The model remained robust in sensitivity analysis. Antenatal lamivudine administration to pregnant patients with hepatitis B is cost-effective, and frequently cost-saving, under a wide range of circumstances.
Article
Unlabelled: Hepatitis B virus (HBV) infection is a global health issue. Universal infantile hepatitis B (HB) vaccination is very efficacious. However, HBV infections among those immunized subjects have been reported. The long-term efficacy of postnatal passive-active HB vaccination in high-risk subjects is not well explored. A total of 8,733 senior high school students who were born after July 1987 were assayed for hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs). The overall HBsAg and anti-HBs-positive rates were 1.9% and 48.3%, respectively. The HBsAg-positive rate was 15% in HB immunoglobulin (HBIG) recipients (adjusted odds ratio [OR]: 15.63; 95% confidence interval [CI]: 10.99-22.22). Among students who did not receive HBIG, there was a significantly negative association between HB vaccination dosage and HBsAg-positive rate (P for trend = 0.011). Adjusted ORs for those who received 4, 3, and 1 to 2 doses were 1.00, 1.52 (95% CI: 0.91-2.53), and 2.85 (95% CI: 1.39-5.81), respectively. Among HBIG recipients, the HBsAg-positive rate was significantly higher in subjects with maternal hepatitis B e antigen (HBeAg) positivity and who received HBIG off-schedule. A booster dose of HB vaccination was administered to 1974 HBsAg- and anti-HBs-negative subjects. Prebooster and a postbooster blood samples were drawn for anti-HBs quantification. The proportions of postbooster anti-HBs titer <10 mIU/mL was 27.9%. Subjects with prebooster anti-HBs titers of 1.0-9.9 mIU/mL had significantly higher postbooster anti-HBs titers than those with prebooster anti-HBs titers of <1.0 mIU/mL (P < 0.0001). Conclusion: Having maternal HBeAg positivity is the most important determinant for HBsAg positivity in adolescents who received postnatal passive-active HB vaccination 15 years before. A significant proportion of complete vaccinees may have lost their immunological memories against HBsAg.
Article
Fetal safety of antiviral therapies is important given the long-term treatment of women with chronic hepatitis B (CHB) infection who may become pregnant. We analyzed neonatal safety data from the Antiretroviral Pregnancy Registry (APR), the largest safety database in pregnancy for antivirals used for HIV and CHB. Data were extracted from APR cases prospectively enrolled between 1989 and 2011. Primary outcomes were major birth defects rates with exposure to all antivirals, individual classes, and drugs compared to population-based controls. Relevant to CHB, only lamivudine (LAM) and tenofovir disoproxil fumarate (TDF) had sufficient individual data for review (⩾200 cases). Of 13,711 cases analyzed, the overall birth defect prevalence (2.8%, 95% CI 2.6-3.1%) was comparable to Centers for Disease Control population-based data (2.72%, 2.68-2.76%, p=0.87) and two prospective antiretroviral exposed newborn cohorts (2.8%, 2.5-3.2%, p=0.90 and 1.5%, 1.1-2.0%, p<0.001). The birth defects prevalence between first and second/third trimesters exposure was similar (3.0% vs. 2.7%). No increased risk of major birth defects with LAM or TDF exposure compared to population-based controls was observed. No specific pattern of major birth defects was observed for individual antivirals or overall. No increased risk of major birth defects including in non-live births was observed for pregnant women exposed to antivirals relevant to CHB treatment overall or to LAM or TDF compared to population-based controls. Continued safety and efficacy reporting on antivirals in pregnancy are essential to inform patients on their risks and benefits during pregnancy.
Article
Women of childbearing age with recognized hepatitis B infection should have their liver disease assessed before pregnancy occurs since the management of hepatitis B virus (HBV) infection in this setting is complex. Initiation of treatment in a woman of child-bearing age will depend on when she intends on conceiving, as well as the severity of her liver disease. During pregnancy, all decisions about initiating, continuing or stopping HBV therapy must include an analysis of the risks and benefits for both mother and fetus. The trimester of the pregnancy and the stage of the mother's liver disease are important factors. Treatment in the third trimester may be considered to aid in prevention of perinatal transmission, which appears to be most pronounced in mothers with high viral loads. Consideration of initiation of third trimester treatment should occur after a high viral load is documented in the latter part of the second trimester, to allow adequate time for initiation of antiviral therapy with significant viral suppression before delivery. This discussion should include the topic of breastfeeding, since it is generally not recommended while on antiviral therapy. Until recently lamivudine and tenofovir appeared to be the therapeutic options with the most reasonable safety data in pregnancy. There are emerging data that telbivudine may also be considered in this setting.
Article
Telbivudine reduces hepatitis B virus (HBV) DNA and normalizes levels of alanine aminotransferase (ALT) in patients with chronic hepatitis B (CHB). We investigated its use in preventing vertical transmission. We performed an open-label, prospective study of 88 hepatitis B (HB) e antigen (HBeAg)-positive pregnant women with CHB, levels of HBV DNA >6 log(10) copies/mL, and increased levels of ALT. Women were given telbivudine (n = 53) starting in the 2nd or 3rd trimester, or no treatment (controls, n = 35) and followed until postpartum week (PPW) 28. All infants received standard immunoprophylaxis after birth. At 28 weeks, none of the infants whose mothers received telbivudine had immunoprophylaxis failure, whereas 8.6% of the infants of control mothers did (P = .029). There were no differences between groups in mothers' adverse events or infants' congenital deformities, gestational age, height, and weight, or Apgar scores. At postpartum week 28, significantly more telbivudine-treated mothers had levels of HBV DNA <500 copies/mL, normalized levels of ALT, and hepatitis B e antigen seroconversion compared with controls (58% vs none, P < .001; 92% vs 71%; P = .008; and 15% vs none; P < .001, respectively) but none had loss of hepatitis B surface antigen. Telbivudine-treated mothers had no virologic breakthrough (HBV DNA >1 log(10) increase from <500 copies/mL) or discontinuations from adverse events. After delivery, 13/52 patients discontinued telbivudine due to preference. There were no episodes of severe hepatitis (levels of ALT >10 times the upper limit of normal) in either group during 28 weeks of postpartum observation. Women with CHB given telbivudine during the second or third trimester of pregnancy have reduced rates of perinatal transmission. Telbivudine produced no adverse events in mothers or infants by 28 weeks.
Article
In infants born to hepatitis B surface antigen (HBsAg)-positive mothers, failure after passive-active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg-positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother-infant pairs. All infants received the identical passive-active immunization schedule after birth. The failure infants (HBsAg positive at 7-12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers' pre-delivery HBV DNA levels were stratified to <6, 6-6.99, 7-7.99 and ≥ 8 log(10) copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)-positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07-3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22-110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg-positive mothers with HBV DNA levels ≥ 6 log(10) copies/mL. The presence of HBV DNA in cord blood predicted failure to passive-active immunization.
Article
In the Asia-Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10-30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×10(7) copies/ml mothers received telbivudine 600 mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200 IU of HBIg within 12 h postpartum and recombinant HBV vaccine of 20 μg at 0, 1, and 6 months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p=0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population.
Article
To evaluate efficacy of lamivudine in reducing in utero transmission of hepatitis B virus (HBV). A database was constructed from Medline, EMBASE, Cochrane Library, National Science Digital Library, China Biological Medicine Database, and through contact with experts in the field from January 1990 to October 2009. We used the Jadad score and Cochrane Collaboration's tool for assessing risk of bias. We abstracted data regarding HBV intrauterine infection, mother-to-child transmission, maternal HBV DNA level, treatment methods, and adverse effects. All newborns followed joint immune prophylaxis schedule of hepatitis B vaccine and hepatitis B immunoglobulin after delivery. The Mantel-Haenszel random-effects model was employed for all analyses using odds ratio (OR) and 95% confidence interval. Newborns in the lamivudine group had a 13.0-23.7% lower incidence of intrauterine infection, indicated by newborn hepatitis B surface antigen (0.38, 0.15-0.94, six randomized controlled trials [RCTs], P=.04) and HBV DNA (0.22, 0.12-0.40, four RCTs, P<.001) seropositivity, and a 1.4-2.0% lower mother-to-child transmission rate at 9-12 months, indicated by infant hepatitis B surface antigen (0.31, 0.15-0.63, four RCTs, P<.01) and HBV DNA (0.20, 0.10-0.39, two RCTs, P<.001) seropositivity. No significant higher adverse effects or complications in pregnancy were observed. Lamivudine in HBV carrier-mothers with high degree of infectiousness in late pregnancy effectively prevented HBV intrauterine infection and mother-to-child transmission.
Article
To analyse preterm birth rates worldwide to assess the incidence of this public health problem, map the regional distribution of preterm births and gain insight into existing assessment strategies. Data on preterm birth rates worldwide were extracted during a previous systematic review of published and unpublished data on maternal mortality and morbidity reported between 1997 and 2002. Those data were supplemented through a complementary search covering the period 2003-2007. Region-specific multiple regression models were used to estimate the preterm birth rates for countries with no data. We estimated that in 2005, 12.9 million births, or 9.6% of all births worldwide, were preterm. Approximately 11 million (85%) of these preterm births were concentrated in Africa and Asia, while about 0.5 million occurred in each of Europe and North America (excluding Mexico) and 0.9 million in Latin America and the Caribbean. The highest rates of preterm birth were in Africa and North America (11.9% and 10.6% of all births, respectively), and the lowest were in Europe (6.2%). Preterm birth is an important perinatal health problem across the globe. Developing countries, especially those in Africa and southern Asia, incur the highest burden in terms of absolute numbers, although a high rate is also observed in North America. A better understanding of the causes of preterm birth and improved estimates of the incidence of preterm birth at the country level are needed to improve access to effective obstetric and neonatal care.