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Telbivudine and Elective Cesarean Section Help Prevent Mother-to-child Hepatitis B Transmission

Treatment with the nucleoside analog telbivudine (Tyzeka) and birth by elective Cesarean section both reduced the likelihood of hepatitis B virus (HBV) transmission from mothers to infants during pregnancy and delivery, according to 2 separate studies presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) this week in Boston. Emergency Cesarean delivery, however, was associated with a trend toward increased transmission risk.

Hepatitis B is easily transmitted from mother to child, and this has historically been a major mode of transmission in parts of Asia where the disease is endemic. Most people infected as babies (about 90%) develop chronic infection, compared with only about 10% of those infected as adults.

Today, giving infants the first dose of the 3-part HBV vaccine series and hepatitis B immune globulin (HBIG, or antibodies) immediately after birth has dramatically reduced the rate of perinatal infection. But use of antiviral agents and changing method of delivery might lower the risk even more.

Telbivudine

C. Pan from Mt. Sinai School of Medicine in New York and colleagues from Nanjing, China, conducted a prospective, non-randomized, open-label study looking at the safety and efficacy of telbivudine during pregnancy for prevention of perinatal HBV transmission.

Despite the use of HBV vaccination and HBIG, perinatal HBV transmission occurs in about 10%-30% of infants born to mothers with high HBV DNA viral load, the researchers noted as background.

This analysis included 190 hepatitis B "e" antigen (HBeAg) positive Asian women between weeks 20 and 32 of pregnancy who had HBV DNA > 6,000,000 copies/mL. The median age was about 26 years and the women had 1 prior pregnancy on average.

Women were either treated with 600 mg/day telbivudine from week 20-32 of gestation through week 4 after delivery, or else received no treatment. Women in the telbivudine arm who had active chronic hepatitis B continued therapy through week 28 post-partum. Infants in both arms received 200 IU HBIG within 24 hours after birth. They received recombinant HBV vaccine doses at birth, 1 month, and 6 months.

Results

• Prior to delivery, the average maternal HBV DNA level dropped considerably in the telbivudine arm (from 8.07 log copies/mL at baseline to 2.35 log copies/mL), while remaining stable in the untreated control arm (from 7.94 to 7.83 log copies/mL).
• 30.04% of women in the telbivudine group achieved undetectable HBV DNA by the time of delivery, compared with none in the untreated arm.
• About half of the infants in both arms were born by Cesarean section, and more than 20% of women in both groups experienced post-partum hemorrhage.
• At birth, 6.32% of newborns in the lamivudine arm were hepatitis B surface antigen (HBsAg) positive, compared with 30.43% in the control arm, a highly significant difference.
• The primary intent-to-treat (missing = failure) analysis at week 28 showed that 2.11% of infants were HBsAg positive or had detectable HBV DNA in the telbivudine arm, compared with 13.04% in the control arm.
• None of the infants born to telbivudine-treated mothers were HBsAg positive, compared with 8.70% of those born to untreated women.
• HBV DNA was detectable only in HBsAg positive infants.
• Telbivudine was well-tolerated and no women discontinued therapy due to adverse events.
• 7.45% of women in the telbivudine arm and 18.48% in the control arm experienced ALT flares 2-5 times the upper limit of normal (x ULN).
• 36 women discontinued telbivudine at week 4 post-partum according to protocol, with no cases of severe hepatitis flares (ALT > 10 x ULN).
• No congenital deformities or birth defects were seen in infants born to treated or untreated mothers.
• There were no differences in gestational age at birth, infant height or weight, or Apgar score between the treated and untreated arms.

"[Telbivudine] used during late pregnancy in chronic hepatitis B HBeAg positive highly viremic mothers can safely reduce perinatal HBV transmission," the researchers concluded. "[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."

Caesarean Section

In the second study, Pan and a different team of colleagues from Beijing looked at the effect of Caesarean delivery on risk of HBV immunoprophylaxis failure in infants born to HBeAg positive women with chronic hepatitis B, defined as infants being HBsAg positive at 7-12 months of age, indicating that they had become infected.

In this analysis, the researchers retrospectively reviewed 1027 consecutive women followed from January 2007 through March 2010. Coinfected women and those who used antiviral drugs during pregnancy were excluded. A total of 569 infants were born to 556 HBeAg positive mothers: 286 by vaginal delivery, 189 by elective Cesarean section, and 94 by emergency Cesarean section. Average HBV DNA levels were similar in all 3 groups.

Again, infants received 200 IU HBIG and the first HBV vaccine dose within 12 hours after birth, 200 IU HBIG again at 2 weeks of age, and additional vaccine doses at 1 and 6 months. Infant serum HBV markers were assessed 1-5 months after completing the HBV vaccine series.

Results

• Perinatal HBV transmission occurred in 5.94% of vaginal deliveries, 2.12% of elective Cesarean sections, and 8.51% of emergency Cesarean sections.
• There were significant differences in the rate of immunoprophylaxis failure between the vaginal delivery and elective Cesarean section groups (P = 0.047) and between the elective and emergency Cesarean groups (P = 0.028), but the difference between the vaginal and emergency Cesarean groups did not reach statistical significance (P = 0.384).
• All cases of immunoprophylaxis failure occurred in infants born to mothers with HBV DNA high levels > 1,000,000 copies/mL.

"[C]ompared with emergency Cesarean section and vaginal delivery, elective Cesarean section was the delivery mode resulting in least perinatal transmission in the mothers with HBeAg positive and high level of HBV viremia," the researchers concluded. "Our data support the use of elective C-section in this population to reduce perinatal transmission."

Investigator affiliations:

Han study: Gynecology & Obstetrics and Infectious Diseases, Second Affiliated Hospital of the Southeast University, Nanjing, China; Gynecology and Obstetrics, School of Medicine, Southeast University, Nanjing, China; Mount Sinai Services at Elmhurst Hospital, Mount Sinai School of Medicine, Flushing, NY.

Zou study: Artificial Liver Center, Beijing You'an Hospital,Capital Medical University, Beijing, China; Deparment of Obstetrics and Gynecology, Beijing You'an Hospital, Capital Medical University, Beijing, China; Mount Sinai Services at Elmhurst Hospital, Mount Sinai School of Medicine, New York, NY.

11/9/10

References

G Han, W Zhao, M Cao, and others. A prospective and open-label study for the efficacy and safety of telbivudine (ltd) in pregnancy for the prevention of perinatal transmission of hepatitis B virus (HBV) to the infants. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 212.

H Zou, Y Chen, Z Duan, and others. A retrospective study for clinical outcome of Caesarean section on perinatal transmission of hepatitis B virus in infants born to HBeAg positive mothers with chronic hepatitis B (CHB). 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 235.