Science Translational Medicine: Infection Could Help Patients' Immune Systems Tolerate Liver Transplant

Viruses aren't typically known for the good things they can do, but a new study reports that a history of hepatitis C infection in liver transplant patients actually restrains the anti-transplant immune responses some patients experience.

In this way, the infection by the virus helps the body tolerate the new organ and may prevent rejection of the transplant. The research appears in the 25 June issue of Science Translational Medicine.

Transplant recipients who have viral infections are typically excluded from clinical trials attempting to improve transplant tolerance, a decision based on previous animal studies showing that infection prevents tolerance.

These new findings contradict what has been shown in animal models and offer evidence that transplant patients with chronic viral infections — almost 40% of the transplant population — may be able to stop taking the drugs used to suppress the body's immune rejection of a transplanted organ. Almost half of all transplant patients get these drugs as part of the normal transplant treatment.

"Our findings highlight the complexities of the interactions between anti-viral and alloreactive immune responses, and the difficulty of predicting the outcome of these interactions on the basis of experimental animal model data," said Alberto Sanchez-Fueyo, a professor of hepatology at Kings College London.

The findings...offer evidence that transplant patients with chronic viral infections — almost 40% of the transplant population — may be able to stop taking the drugs used to suppress the body's immune rejection of a transplanted organ.

Sanchez-Fueyo and colleagues stopped immunosuppressive therapy in 34 hepatitis C-infected liver transplant recipients and found that about half of the patients successfully retained their transplant even after one year of being completely off the drugs.

Taking a closer look, the researchers discovered that a trick viruses commonly use to avoid being detected by the immune system — rewiring immune cells so that they become immunosuppressed — can create an immune environment that facilitates transplant tolerance. In fact, the patients who tolerated the transplant were more likely than the other patients to have certain immune cells that were "exhausted" by the virus.

Essentially, the virus does some of the immune-squelching work that immunosuppressive drugs do. The researchers aren't sure if this effect happens in transplanted organs in other parts of the body, but the results shed light on the unexpected influence chronic viral infections have on transplant tolerance. The findings could influence the design of future clinical trials attempting to induce tolerance.

"What we need to urgently clarify now is how immunosuppressants need to be managed once hepatitis C virus infection has been eradicated," said Sanchez-Fueyo, "and whether in these patients transplantation tolerance persists in the absence of infection."