Bob Roehr

November 08, 2010

November 8, 2010 (Boston, Massachusetts) — Limited use of telbivudine in highly viremic pregnant women can reduce perinatal hepatitis B virus (HBV) transmission to infants, according to the results of a study presented here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting. The study was conducted in Nanjing, China, and presented by Calvin Pan, MD, from Mount Sinai Services at Elmhurst Hospital, Mount Sinai School of Medicine in Flushing, New York, on behalf of his colleagues in Nanjing.

Perinatal transmission of HBV is quite common in Southeast Asia and in Asian communities in other parts of the world, even several generations after migration from that region. Despite immunoprophylaxis, HBV transmission continues to occur at rates of 10% to 30% in children born to mothers who are highly viremic, he said.

Previous studies have shown that lamivudine used in the third trimester of pregnancy can significantly reduce HBV transmission. However, the incidence of teratogenicity with telbivudine in animals has restricted its use in pregnant women.

Dr. Pan said the open-label case–controlled study of telbivudine in highly viremic hepatitis B e antigen positive (HBeAg+) mothers was undertaken to assess its efficacy and safety in pregnant women and their offspring. It was the first such study of the drug. A placebo-controlled randomized trial might have raised ethical concerns, given the data on lamivudine. There also was the practical fact that some women knew of and desired prevention intervention and would not have agreed to randomization to placebo.

To participate in the study, the women had to be HBeAg+, have serum HBV DNA levels above 1.0 × 6 log10 copies/mL, and have been screened between 20 and 32 weeks of gestation. It enrolled 95 women who wished to take telbivudine, and a similar number who did not.

Women in the active group received 600 mg/day telbivudine beginning between weeks 20 and 32 of gestation, and continued on it for at least 4 weeks after delivery. Women with elevated alanine transaminase levels had the option of remaining on therapy, and 20% to 30% chose to do so. Physical and laboratory examinations were conducted at baseline, at delivery, and at weeks 4 and 28 after delivery.

"At baseline, both the control arm and the telbivudine arm had HBV DNA of about 8 logs, but at delivery, the mothers in the treatment arm had a tremendous reduction, of about 2.3 logs. About 30% of those on treatment had undetectable [HBV DNA levels]," or less than 1000 copies/mL, said Dr. Pan.

Prior to delivery, HBV DNA levels were 2.35 log10 copies/mL (1.79 standard deviation [SD]) in the treated group, and 7.83 log10 copies/mL (0.67 SD) in the control group (P < .001). The rates of newborns positive for HBV surface antigen (HBsAg+) at birth were 6.32% and 30.43%, respectively (P < .001).

All infants were vaccinated with 200 IU of hepatitis B immunoglobulin within 24 hours of delivery, and with recombinant HBV vaccine 20 μg at birth and at 1 and 6 months. They were tested for HbsAg and HBV DNA at birth and at 28 weeks of age.

At the week-28 end point, according to an intent-to-treat analysis, 2.11% of infants in the active treatment group and 13.04% in the placebo group were either HBsAg+ or had detectible levels of HBV RNA. HBV DNA was only detected in HBsAg+ infants.

Safety proved not to be an issue. There were no discontinuations because of adverse events, and there were no congenital defects that might be attributed to telbivudine.

Anna S. F. Lok, MD, from the University of Michigan in Ann Arbor, congratulated the authors on an excellent study. She asked if there was a threshold level of HBV DNA below which the mother did not transmit virus to the child. Dr. Pan said that analysis on that has not yet been done.

"It's a wonderful study," said Jay H. Hoofnagle, MD, director of the Liver Disease Research Branch of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland. "I think that randomization is overstressed as an important way to control things. [In this study], you have very nicely balanced groups."

Dr. Hoofnagle said he has no explanation for why the portion of infants who were HBeAg+ or had detectable HBV RNA declined from birth to week 28.

Dr. Pan believes it probably was "a technical issue. We didn't have a very sensitive [polymerase chain reaction] — we were using a cut-off of 1000 — so those patients might simultaneously be DNA-positive."

The Chinese Department of Health underwrote the study with no industry support. None of the physicians have disclosed any relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 212. Presented November 2, 2010.

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