Singapore: A Singapore led study has shown that Hepatitis B Virus Infection
(HBV) exposure increases the immune system maturation of infants, which
may give a better survival advantage to counteract bacterial infection
during early life. These findings radically modify the way that HBV
vertical infection of neonates (mother-to-child) is portrayed, and
present a paradigm shift in the approach to treatment of patients with
chronic hepatitis B.
Currently widespread in Asia, HBV affects approximately 300 million
people worldwide while 6 in 100 Singaporeans are chronic carriers. The
majority of HBV chronic infections in Asia are acquired at birth. While
there is a safe and effective vaccine available, 5% to 10% of babies
born to HBV positive mothers still contract the infection.
Conventionally, HBV is thought to exploit the immaturity of the neonatal
immune system to establish persistent infection.Current guidelines from international liver associations recommend
treatment for HBV carriers only when they show clear signs of active
liver disease, typically after the age of 30. This is based on the
assumptions that HBV is considered harmless until symptoms of the
disease emerge, and that young patients are immune-tolerant to HBV,
meaning they have no protective response to the virus and are unable to
react to treatment.
Prof Bertoletti, in collaboration with the National University
Hospital (Singapore) and Universitaria di Parma (Italy), showed that
contrary to current belief, infants exposed to HBV are not
immune-tolerant but they have more mature immune systems. The team
examined the immune cells in the cord blood of mothers who were HBV
positive and discovered that both the innate and adaptive immune cells
are more activated and mature, and they respond better to bacteria
challenge, a phenomenon called “trained immunity”. These suggest that
their immune cells may be more acclimatised to dealing with potential
bacterial infections than the cells from cord blood of healthy mothers.
First author, Duke-NUS Research Fellow Michelle Hong, is heartened
about contributing to the understanding of a disease that is endemic in
Asia. “Our work contributes to the understanding of how HBV exposure
before birth shapes the global immune response of newborn infants and
transforms the way we look at HBV. Despite causing diseases later in
life, HBV might actually be beneficial to humans early in life.”
Previously, Prof Bertoletti had shown that young adults (aged 14 to
30) with chronic HBV infection are not immune tolerant and possess
immune cells able to counter the virus. Moving forward, he plans to
examine the impact of HBV infection in paediatric patients; those aged
two to 12, to determine how their immune system responds to the virus.
The combined findings from these different studies are poised to shape
the guidelines for chronic HBV treatment in patients – starting from
young adults’ or even earlier.
This research is supported by the Singapore National Research
Foundation under its STaR Investigator Award (NMRC/STaR/0013/2012)
administered by the Singapore Ministry of Health’s National Medical
Research Council and the Agency for Science, Technology and Research.
Follow this link for the full text of the study.