Hepatitis 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 controlled trial

Abstract

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 known. 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. The 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 infection.

World Hepatitis Day in Burkina Faso, 2016: Awareness, Screening, Identification of HBV Markers, HBV/HCV Coinfection, and Vaccination

“…This prevalence rate is lower than the prevalence reported among pregnant women in Burkina Faso in previous studies (11.1% and 31.4%, respectively) (31,32). However, other studies have shown that presence of HBeAg is a risk factor for HBV transmission and chronicity (33,34). The variations in HBeAg rates could be explained by the differences in the study populations.…”

Telbivudine Prevents Vertical Transmission of Hepatitis B Virus From Women With High Viral Loads: A Prospective Long-Term Study

“…Recent studies have shown that maternal serum viral load in the third trimester of gestation is correlated closely with HBV infection of their infants, although MTCT could not be prevented completely by active-passive combination immunization. [12][13][14] Both the 2012 European Association for the Study of the Liver (EASL) and Asian Pacific Association for the Study of the Liver (APASL) Clinical Practice Guidelines recommended that oral antiviral drugs, including telbivudine and tenofovir, can be used in pregnant women. 15 In clinical practice, with prolonged use of oral antiviral drugs in HBV-infected pregnant women, the safety profiles of telbivudine, lamivudine, and tenofovir have been confirmed in various studies.…”

Limited benefit of hepatitis B immunoglobulin prophylaxis in children of hepatitis B e antigen-negative mothers

“…There are also concerns that vaccination with HBIg may blunt long-term immunological responses in the infants (7,8) and increase the risk of occult HBV infection. (9) In the present study, only one sibling was found to have true immunological vaccine failure and two infants were found to have occult infection. Larger, cost-effective analyses will be needed to determine the risks and benefits of universal HBIg immunisation against the cost of prenatal testing for maternal viral load and giving HBIg to those who have detectable HBV DNA.…”

“…These surface gene mutants, which have been associated with HBIg administration, (9) were not detected in their respective mothers. Surface gene mutants have been previously described in studies conducted in Singapore, (4) Taiwan (8,10) and India.…”

“…Surface gene mutants have been previously described in studies conducted in Singapore, (4) Taiwan (8,10) and India. (9) With Singapore's current adoption of the administration of universal hepatitis B vaccination and HBIg, we may see a higher prevalence of these surface mutants in the future, especially since the same recombinant vaccine that was used in the aforementioned studies (where surface gene mutants were observed) is being used in Singapore.…”