A 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

Background & Aims

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.

Methods

Two hundred and twenty-nine HBeAg+ HBV DNA levels >1.0 × 10⁷ 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.

Results

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.

Conclusions

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.

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.