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 (IS) drugs. A number of clinical trials have intentionally withdrawn IS drugs from stable patients, but none of these trials have investigated the mechanisms through which tolerance develops in patients with persistent hepatitis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, published in the journal Science Translational Medicine, 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infected with HCV were selected for enrollment on a clinical trial in Spain, in which their IS drugs were gradually withdrawn and their health monitored over the following year.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, Head of the Institute of Liver Studies at King's College London and co-author of the study, says: “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.
Notes to editors
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‘HCV-induced immune responses influence the development of operational tolerance following liver transplantation in humans’, by Bohne et al, is published in the journal Science Translational Medicine on Wednesday 25 June 2014.
The international study was carried out by the University of Barcelona, Irsicaixa AIDS Research Institute in Barcelona, University of Valencia, Medical School of Hannover, Helmholtz Zentrum München, and King’s College London.