— Christine M. Kukka, Project Manager, HBV Advocate
A new study suggests for the first time that the
combination of the hepatitis B vaccine and HBIG (hepatitis B
immune globulin) may be ineffective in preventing "occult"
hepatitis B in babies born to mothers infected with the hepatitis
B virus (HBV). An occult infection occurs when a person tests
negative for the hepatitis B surface antigen (HBsAg)—considered
an essential antigen building block for HBV—while testing
positive for HBV DNA. When this occult infection occurs,
researchers suspect the HBsAg has somehow mutated so conventional
lab tests can't identify it.
In the recent study, published in the November issue of the Journal of Viral Hepatitis,
researchers compared outcomes in babies born to infected mothers
who were given only the vaccine or a combination of the vaccine
and HBIG, which is composed of hepatitis B surface antibodies
derived from humans. They found that occult HBV infection
occurred in 42% of 222 babies two years after their births. Most
of the children with occult infections had received both the
vaccine and HBIG, leading researchers to suggest that HBIG may
play a role in promoting the development of an occult infection,
or else the mothers may have received antiviral treatment that
led to the HBsAg mutation.
B vaccination with or without hepatitis B
immunoglobulin at birth to babies born of
HBsAg-positive mothers prevents overt HBV transmission but
may not prevent occult HBV infection in babies: a randomized
Pande C, et al..
Department of Gastroenterology,
GB Pant Hospital, New Delhi, India; Special Centre for
Molecular Medicine (SCMM), Jawaharlal Nehru University (JNU),
New Delhi, India.
J Viral Hepat. 2013 Nov;20(11):801-10. doi: 10.1111/jvh.12102. Epub 2013 Apr 23.
Vertical transmission of Hepatitis B virus HBV
can result in a state of chronic HBV infection and its
complications. HBV vaccination with or without hepatitis
B immunoglobulin (HBIG) prevents transmission
of overt infection to the babies. However, whether it
also prevents occult HBV infection in babies is not
Consecutive pregnant women of any gestation found to be HBsAg
positive were followed till delivery, and their babies were
included in the study. Immediately after delivery, babies were
randomized to receive either HBIG or placebo in addition to
recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary
end-point of the study, assessed at 18 weeks of age, was
remaining free of any HBV infection (either overt or
occult) plus the development of adequate immune response to
vaccine. The babies were further followed up for a median of
2 years of age to determine their eventual outcome. Risk factors
for HBV transmission and for poor immune response in babies were
studied. Of the 283 eligible babies, 259 were included in
the trial and randomized to receive either HBIG (n = 128) or
placebo (n = 131) in addition to recombinant HBV vaccine.
Of the 222 of 259 (86%) babies who completed 18 weeks of
follow-up, only 62/222 (28%) reached primary end-point. Of the
remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%)
developed occult HBV infection, and 12/222 (5%) had no HBV
infection but had poor immune response. All 6 overt infections
occurred in the placebo group (P = 0.030), while occult HBV
infections were more common in the HBIG group (76/106 [72%] vs.
66/116 [57%]; P = 0.025). This may be due to the immune pressure
of HBIG. There was no significant difference between the two
groups in frequency of babies developing poor immune response or
those achieving primary end-point.
The final outcome of these babies at 24 months of age was as follows:
- overt HBV infection 4%,
- occult HBV infection 42%,
- no HBV infection but poor immune response 8%
- and no HBV infection with good immune response 28%.
Women who were anti-HBe
positive were a low-risk group, and their babies were most likely
to remain free of HBV infection (occult or overt) and had
good immune response to the vaccine. Maternal HBeAg-positive
status and negativity for anti-HBe predicted not only overt but
also any infection (both overt and occult) in babies.
In addition, high
maternal HBV DNA and treatment with vaccine alone were
significant factors for overt HBV infection in babies.
current practice of administration of vaccine with HBIG at birth to
babies born of HBsAg-positive mothers is not effective in
preventing occult HBV infection in babies, which may be up to
40%. Because the most important risk factors for mother-to-baby
transmission of HBV infection are the replicative status
and high HBV DNA level in mothers; it will be worthwhile
investigating the role of antivirals and HBIG administration
during pregnancy to prevent mother-to-child transmission of HBV
Labels: mother-to-child transmission, Occult HBV, perinatal transmission, vaccines