Research ArticleA prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection
Introduction
Hepatitis B virus (HBV) infection is a serious clinical problem affecting approximately 2 billion people worldwide. In the Asia–Pacific region, the vertical transmission of HBV from hepatitis B surface antigen (HBsAg)-positive mothers to their infants at birth or in early infancy is a key factor in the endemicity of HBV infection, and is associated with an increased risk of developing chronic hepatitis B (CHB) [1], [2]. Perinatal transmission of HBV can be prevented in most newborns whose mothers are HBsAg positive, through passive or active immunization administered within 12 h of birth [3]. Evidence from long-term follow-up studies on the impact of the implementation of universal HBV vaccination programs in Taiwan has demonstrated that the prevention of mother-to-child transmission is associated with a substantial reduction in HBV infection [4], [5], [6], [7].
However, immunoprophylaxis against HBV fails in 10–15% of infants [8], [9], mainly as a result of vertical infection. A positive correlation has been noted between high maternal serum HBV DNA levels and an increased risk for vaccination breakthrough [10], [11], [12], [13], [14]. This suggests that a high level of maternal viremia is an important factor in prophylaxis failure. Treatment with the oral nucleoside analog lamivudine during the last month of pregnancy in highly viremic mothers has been shown to reduce mother-to-infant transmission and the risk of vaccination breakthrough in infants who received passive–active immunoprophylaxis [15], [16]. Telbivudine, a potent oral nucleoside analog licensed for the treatment of patients with CHB, has demonstrated faster and superior efficacy to lamivudine in patients with HBeAg-positive and HBeAg-negative CHB disease [17], [18]. In the randomized phase III GLOBE trial, telbivudine was associated with a higher rate of serum HBV DNA negativity, alanine aminotransferase normalization, and hepatitis B e antigen (HBeAg) loss and seroconversion than was lamivudine at 1 and 2 years in HBeAg-positive patients. To date, limited data are available on the safety and efficacy of telbivudine treatment during pregnancy and its effect on perinatal HBV transmission.
In the present study, we evaluated the effect of telbivudine given during the second and third trimesters of pregnancy to highly viremic, HBV DNA-positive mothers on maternal HBV DNA and HBeAg levels prior to delivery and the rate of vertical transmission of HBV to infants who received passive–active immunoprophylaxis. Additionally, we investigated the safety of telbivudine during pregnancy.
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Patients and methods
Pregnant women who were HBsAg positive during their visit to the Department of Gynecology and Obstetrics of the Second Affiliated Hospital of the Southeast University, Nanjing, China, between December 2007 and August 2009 were screened for eligibility to enroll in the study according to the following inclusion criteria: age, 20–40 years; gestational age, 20–32 weeks; positivity for serum HBsAg and HBeAg; and HBV DNA levels >1.0 × 107 copies/ml (lower limit detection <500 copies/ml). Patients were
Results
A total of 234 mothers were enrolled, 137 mothers were in the telbivudine-treated group and 97 were in the control group. But 5 patients withdrew from the study before the start of intervention (3 in control group and 2 in telbivudine group) due to their change of minds. None of the remaining patients were lost to follow up or dropped out during their pregnancy. In the telbivudine-treated group, 4 pairs of mothers and infants were lost after one month postpartum. There were 97 mothers with
Discussion
In the European Union and North America, where there is a relatively low prevalence of HBV, it has become common to prevent HBV maternal-infant transmission by employing a combination of active and passive immunization. In China, where the prevalence of HBV is high, 85–90% of transmissions can be prevented successfully. However 10–15% of cases result in immunoprophylaxis failure due to intrauterine infection, and the subsequent development of chronic HBV infection. A correlation between
Conflict of interest
The authors who have taken part in this study do not have a relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research. The Authors received support from a research grant for Projects in Infectious Diseases from the Department of Health, Jiansu Province, P.R. China. (Research Grant Number: H200804).
Acknowledgment
We appreciate the guidance provided by Professor Zhi-Xun Fang of our hospital, to the study. And we are grateful for the editorial assistance provided by Doctor Kathleen Covino.
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