BOSTON – The recombinant hepatitis B vaccine confers as much protection when given alone as it does when given together with hepatitis B immunoglobulin to newborns of chronically infected mothers, but neither regimen is optimally effective, a study has shown.
The randomized controlled trial assessed the hepatitis B virus (HBV) status of 222 infants born to mothers who tested positive for hepatitis B surface antigen (HBsAg). The rate of protection observed in infants who received only the vaccine was statistically similar to that of infants who received the vaccine plus hepatitis B immune globulin (HBIG).
A total of 39% of the vaccine-only group and 41% of the combination group remained infection free at a minimum of 18 weeks after birth, Dr. Shiv K. Sarin reported at the annual meeting of the American Association for the Study of Liver Diseases, noting that nearly half of the babies in both groups developed occult HBV infections.
The current standard of care for preventing HBV infection in babies born to mothers who are HBsAg positive is the recombinant hepatitis B virus vaccine plus HBIG, however previous studies have suggested the possibility that the vaccine alone may be as effective as the combination therapy, said Dr. Sarin of the Institute of Liver and Biliary Sciences in New Delhi.
To test this hypothesis, Dr. Sarin, along with lead investigator Dr. Chandana Pande, a research associate at G.B. Pant Hospital in New Delhi, and colleagues randomized the newborns of 222 women who screened positive for HBsAg during their prenatal care to receive the 0.5-mL recombinant HBV vaccine at birth, 6 weeks, 10 weeks, and 14 weeks, either alone (116 infants) or with 0.5 mL intramuscular HBIG (106 infants). Mothers on antiviral therapy and those with coinfections were excluded from the investigation, he said.
All of the babies were assessed at a minimum of 18 weeks for HBsAg, HBV-DNA, and antibodies to HBsAg (anti-HBs). The study’s primary end point was freedom from overt or occult HBV infection with adequate immune response, defined as anti-HBs titers of at least 10 IU/mL, Dr. Sarin said in a poster presentation.
Babies with overt HBV infection were those whose blood specimens tested positive for HBsAg by enzyme-linked immunosorbent assay, whereas babies with occult infection were negative for HBsAg but positive for HBV-DNA by polymerase chain reaction testing, he said. Babies with no infection but whose anti-HBs titers were less than 10 IU/mL were categorized as having a poor immune response.
At 18 weeks after birth, there were no significant differences between the combination therapy group and monotherapy group with respect to the number of babies meeting the study’s primary end point, Dr. Sarin reported. Specifically, 43 babies in the combination group and 45 in the vaccine-only group remained free of overt or occult HBV infection with adequate immune response, he said.
Of the babies not meeting the primary end point, 9 had overt HBV infection, including 2 in the combination group and 7 in the vaccine-only group, and 106 developed occult HBV infection, including 52 in the combination group and 54 in the vaccine-only group, Dr. Sarin said. Neither of these differences attained statistical significance, nor did the between-group difference in the number of infants demonstrating a poor immune response, he said. Nineteen babies in the combination group and 10 in the vaccine-only group had anti-HBs titers lower than 10 IU/mL.
The large number of babies in both groups who developed occult HBV infection "may be due to intrauterine transmission of the infection," Dr. Sarin suggested. The findings highlight the need for trials of antiviral agents during pregnancy in order to prevent cases in which immunoprophylaxis strategies need to be used, but then fail, he stressed.
Dr. Sarin and Dr. Pande said they had no relevant financial disclosures.