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Nature Reviews Gastroenterology & Hepatology| Published online 24 Jan 2018;
doi:10.1038/nrgastro.2018.6
Biomarker for HBV therapy discontinuation
Lifelong nucleoside or nucleotide
analogue (NUC) therapy is the current
treatment of choice for patients with
chronic hepatitis B (CHB). However,
a new study has shown that an
HBV-specific T cell biomarker can predict
the safe discontinuation of NUC therapy.
NUC compounds can suppress HBV
replication but cannot fully eradicate
the virus. Accordingly, this therapy is
maintained for life in most patients with
CHB, and discontinuation can lead to
virological relapse and hepatic flare.
However, some patients are able to
control the infection without ongoing
treatment, and there is evidence that
components of immunity, particularly
T cells, are necessary for HBV control
and avoidance of liver damage.
“We decided, therefore, to test
whether we can identify immunological
biomarkers predicting the safe
discontinuation of antiviral therapy in
patients with CHB,” explains author
Antonio Bertoletti. The researchers
longitudinally studied the immune
profiles of two cohorts of patients (n = 19 and 27) with CHB who controlled
HBV or relapsed upon NUC antiviral
therapy discontinuation. The functional
profiles of antigen-specific T cells
were characterized before and after
the discontinuation of NUC therapies
using standard immunological
assays, along with analyses of global
non-antigen-specific immune
cell populations.
“We show that patients who do not
relapse upon therapy withdrawal
are characterized, during treatment,
by an increased frequency of PD1+
HBV-specific T cells directed against
nucleocapsid and polymerase proteins
of HBV,” reports Bertoletti. “In addition,
our study highlights the neglected
beneficial role that inhibitory molecules
play in the long-term persistence of
partially exhausted T cells specific for
chronic antigens.”
As their current method is too
complicated for routine clinical use, the
investigators are now looking to develop
alternative methods to directly quantify
PD1+ HBV-specific T cells. “Our findings
could lead to a change in the clinical
management of patients with CHB,”
concludes Bertoletti. “The possibility
to better define which patients can
safely stop treatment will allow studying
the virological and immunological
consequences of treatment withdrawal
in more detail.”
Iain Dickson
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发表于 2018-2-24 15:13