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      Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission : Outcomes of telbivudine treatment during pregnancy

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          Abstract

          This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.

          Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth.

          Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen.

          Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication.

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          Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

          Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.
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            Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study.

            This randomized, double-blind, placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26-30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudine-treated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo-treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted as failures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% in the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine-treated mothers or their infants. Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization.
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              An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus.

              Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We analyzed methods of risk assessment and interventions for MTCT. We reviewed 63 articles and abstracts published from 1975-2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6-12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%-30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10(6) copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                October 2016
                07 October 2016
                : 95
                : 40
                : e4847
                Affiliations
                Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
                Author notes
                []Correspondence: Yuzhu Yin, Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China (e-mail: yzzst2011@ 123456163.com ).
                Article
                04847
                10.1097/MD.0000000000004847
                5059039
                27749537
                0750f1b5-8743-4340-982b-7a2d7c2710c4
                Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

                History
                : 11 November 2015
                : 14 July 2016
                : 17 August 2016
                Categories
                5600
                Research Article
                Observational Study
                Custom metadata
                TRUE

                antiviral therapy,hepatitis b virus,mother-to-child transmission,pregnancy

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