Transplant patients can develop tolerance to new livers even if
they have hepatitis C, according to a new study led by King's
College London and the University of Barcelona.
Contrary to what was previously thought, infected patients are
not at greater risk of organ rejection and their heightened immune
response may actually help the body to adapt to a new liver.
The liver is less susceptible to rejection following a
transplant than many other organs, and liver transplant patients
can develop 'operational tolerance' to the new graft, which allows
them to discontinue immunosuppressant drugs. A number of clinical
trials have intentionally withdrawn immunosuppressant drugs from
stable patients, but none of these trials have investigated the
mechanisms through which tolerance develops in patients with
persistent hepatitis C virus infection.
Hepatitis C virus (HCV) chronically infects around 200 million
people worldwide and is responsible for a large number of liver
transplants in the Western World. Following liver transplantation,
HCV infection universally recurs and induces chronic hepatitis in
the new graft. The mechanisms by which HCV reactivates and damages
the new liver are not well understood, but these immune responses
were previously thought to prevent the body from establishing
transplant tolerance.
The new study explored the basis of cross-reactivity between
hepatitis C and transplanted organs, to establish whether the
immune response to a viral infection had a positive or negative
effect on organ tolerance. Thirty-four liver recipients infected
with HCV were selected for enrollment on a clinical trial in Spain,
in which their immunosuppressants were gradually withdrawn and
their health monitored over the following year. Drug withdrawal was
successful in 17 patients (50%), who showed stable liver function
and no signs of organ rejection 12 months after ending their drug
treatment.
Professor Alberto Sanchez Fueyo of King's College London said:
"Our findings challenge a well-entrenched notion that having a
viral infection will prevent you from adapting to a new organ.
Hepatitis C may actually help the body to become tolerant by
dampening the immune response that normally leads to organ
rejection.
"However, more work is needed to understand why some patients
become tolerant while others continue to reject the liver, and how
someone's genetic make-up, type of infection, degree of exposure
and type of graft influence their ability to adapt to a transplant.
We also need to better understand whether completely eradicating
hepatitis C from transplant patients might prevent them from being
able to stop taking immunosuppressants."
The paper, HCV-induced
immune responses influence the development of operational tolerance
following liver transplantation in humans, is published inScience Translational Medicine.