Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus

• Assessment of the safety of TDF, measure the number of participants and paired infants with adverse events [ Time Frame: From the date of randomization until 28 weeks of postpartum. ] [ Designated as safety issue: Yes ]
• Measure the number of infants who have HBV infection at the age of 28 weeks [ Time Frame: From the date of birth to age of 28 weeks ] [ Designated as safety issue: No ]

• Measure the number of patients with ALT normalization at the end of the study compared to the baseline [ Time Frame: From the date of randomization until 28 weeks of postpartum. ] [ Designated as safety issue: Yes ]
• Measure maternal HBV DNA reduction during the study period when compared to the baseline [ Time Frame: From the date of randomization until 28 weeks of postpartum. ] [ Designated as safety issue: Yes ]

Immunoprophylaxis failure of Hepatitis B (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to HBeAg positive mothers with high levels of HBV DNA. Maternal HBV DNA > 6log10 copies/mL is the major risk for the mother-to-child transmission. Prior studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients.

Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum ALT in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study:

1. The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA > 6log10 copies/mL during late pregnancy and infants
2. Its efficacy in the reduction of HBV vertical transmission rate

Eligible mothers will be randomized (1:1)to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 post-partum; follow up will continue until post-partum of week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group

• Hepatitis B Infection
• Chronic Infection
• Viremia

• No Intervention: HBIG, HB vaccine
  Provide standard of care to mothers and standard immunoprophylaxis to their infants
• Experimental: TDF treatment arm
  tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants
  Intervention: Drug: TDF treatment

Inclusion Criteria:

• documented CHB infection with HBsAg positive > 6 months
• HBeAg+ CHB pregnant women
• gestational age between 30-32 weeks
• HBV DNA > 6 log10 copies/mL
• both mother and father of the child are willing to consent for the study

Major Exclusion Criteria:

• co-infection with hepatitis A, C, D, E,HIV or STD
• decompensated liver disease or significant co-morbidity
• history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy
• antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir.
• requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids
• the biological father of the child had CHB
• clinical signs of threatened miscarriage in early pregnancy
• evidence of hepatocellular carcinoma
• maternal ALT > or = 5 x ULN U/mL, or Total Bilirubin > or = 2, or GFR < 100, or Albumin < 25 g/L
• evidence of fetal deformity by ultrasound examination
• patient is participating other clinical study