A
computer-generated image of the hepatitis B virus
Contrary
to conventional wisdom, exposure to the hepatitis B virus activates immunity in
young people, suggesting benefits for earlier treatment
Infectious disease experts have long thought
that children, teenagers and young adults who are chronically infected with the
hepatitis B virus (HBV) lack the immune cells needed to fight this pathogen.
As such, physicians currently withhold
therapeutic interventions from younger patients until they have reached an
advanced age — typically around 30 years old — at which time the immune system
is thought to have ‘awakened’ to the virus.
Yet, contrary to the conventional medical
wisdom, new research from the A*STAR Singapore Institute for Clinical Sciences
(SICS) indicates that there is no such inherent age-associated period of
so-called ‘immune tolerance’ to HBV. In fact, older people with chronic
hepatitis B seem to have a weaker immune response, represented by weaker
antiviral T-cell repertoires, than younger individuals infected with the
virus1.
“These findings can have major implications
for the clinical management of chronic hepatitis B infections,” says the SICS’s
Antonio Bertoletti, who led the research. “It might be better to start
treatment early, as young people have a less compromised HBV-specific immune
response, and [because] functional recovery of HBV-specific T cells is
associated with successful control of the infection.”
Scientists from Bertoletti’s laboratory,
together with clinical collaborators in the UK, isolated T cells from 44 people
with chronic HBV infections between the ages of 10 and 30, the majority of whom
were of Asian descent. Around 75% of the world’s 400 million people with
chronic hepatitis B can be found within the region of Asia.
They compared the immune samples to those
from healthy age-matched controls, and showed that young patients infected with
HBV expressed increased levels of virus-associated T cells, and these T cells
displayed the ability to expand and produce pro-inflammatory signaling
molecules known as cytokines, which are involved in antiviral responses.
Furthermore, these HBV-specific T cells became more dysfunctional with age, the
authors found, suggesting that the longer a patient is left untreated, the less
effective the immune system becomes at clearing the virus.
The study upends the idea that immune
recognition of HBV is somehow averted in certain individuals, thus indicating
that all patients, regardless of age, could be suitable for treatment. It also
highlights the inadequacy of measuring biomarkers of liver inflammation — the
current proxy for immune activity in people with chronic hepatitis B
infections. Such indicators are typically absent in young patients despite the
study's suggestion of the presence of active T-cell responses to the virus.
The A*STAR-affiliated researchers
contributing to this research are from the Singapore Institute for Clinical Sciences
References
- Kennedy, P. T. F., Sandalova, E., Jo, J., Gill,
U., Ushiro-Lumb, I. et al. Preserved T-cell function in
children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology 143, 637–645
(2012). | article
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