Worldwide 240 million people have chronic hepatitis B and 780,000 people
die each year from the liver cirrhosis and cancer that it causes.*; existing
treatments can rarely cure this infection. A preventative vaccination against
the virus is available, however it is not routinely given in the UK and is of
no use once you have the infection. Liver disease is the only major cause of premature
death currently increasing in the UK, and hepatitis B and C are the second
commonest underlying causes after alcohol.
Most adults’ immune systems can control hepatitis B virus within a year
(acute infection), but chronic infection is common in children, particularly in
newborns whose mothers carry the virus, and lasts a lifetime. The new study,
published in Nature Medicine, suggests
that hepatitis B can persist by taking advantage of suppressor cells in the
liver that starve immune responses to silence them.
"If these cells can prevent immune cells from damaging the liver in hepatitis B patients, perhaps they could help to prevent immune rejection of transplanted livers". Professor Mala Maini
“Hepatitis B patients usually don’t have symptoms for decades, so can
carry the virus unknowingly and can spread it through childbirth, sexual
contact or contaminated needles,” says senior author Professor Mala Maini (UCL
Infection & Immunity). “Our work has shown that during this ‘silent phase’
of infection, specialised suppressor cells switch off the immune response by cutting off its food supply. This is
one of the many ways the liver protects itself from inflammation and immune
damage but at the same time, prevents elimination of pathogens like hepatitis B.
“If we could boost the immune system and counteract the liver’s suppressive
effect, then the infection could potentially be cleared after a large ‘burst’
of immune activity. This might cause short-term damage to the liver, but would
prevent the long-term damage from scarring and liver cancers that we see in
chronic patients.”
The team compared blood samples from 138 chronic hepatitis B patients and
99 healthy controls, and examined liver tissue samples from 42 patients. They
found that patients in the silent phases of infection had high levels of cells
called granulocytic myeloid-derived suppressor cells (gMDSCs). These gMDSCs,
which suppress T cells (immune cells) by cutting off their food
supply, were found to accumulate in the liver.
“The gMDSCs suppressed both the T cells that fight hepatitis B virus and
those that cause inflammation in the liver,” explains lead author Dr Laura
Pallett (UCL Infection & Immunity). “So patients with more gMDSC tended to
have less liver damage but were unable to control hepatitis B virus. Women had
higher levels of gMDSC than men, which fits with their threefold lower risk of
developing liver inflammation from hepatitis B.”
These findings emphasise how nutrient supplies can regulate the immune
system. They also suggest that suppressor cells such as gMSDC might have clinical
uses in cases where the immune system attacks healthy tissue, such as
autoimmune diseases or immune rejection of donated organs.
“If these cells can prevent immune cells from damaging the liver in
hepatitis B patients, perhaps they could help to prevent immune rejection of
transplanted livers,” says Professor Maini. “Similarly, such suppressor cells
could potentially be harnessed to protect specific organs from damage in
patients with autoimmune diseases.”
The work was a collaboration between researchers at UCL, Barts and The
London School of Medicine and Dentistry, King’s College London, the University
of Dundee, Duke-Nus Medical School, the Singapore Institute for Clinical
Sciences and Newcastle University.