New technology teaches the immune system to accept a transplanted liver without medication

Researchers have successfully stopped immunosuppressant drugs in several liver transplant patients for more than three years, through a unique, first-of-its-kind clinical trial based on "immunoassay"

Researchers have successfully stopped immunosuppressant drugs in several liver transplant patients for more than three years, through a unique, first-of-its-kind clinical trial based on "immunoassay".

The recent study, the results of which were published in the journal Nature Communications, was conducted by UPMC Medical Center and the University of Pittsburgh. 

The researchers confirmed that it is possible and safe to give recipients of a living donor liver transplant an injection of immune cells derived from the donor a week before the transplant, and then, after a year, begin withdrawing immunosuppressant drugs.

Although necessary to prevent organ rejection, long-term use of immunosuppressant drugs causes serious side effects, including kidney damage, metabolic complications, and makes patients more susceptible to infections, certain types of cancer, and diabetes.

Lead author Angus Thompson, a professor of surgery and immunology at the University of Pittsburgh, says that relieving patients of these effects was a goal that researchers in Pittsburgh, under the direction of the late Thomas Starzl, began three decades ago.

The liver has a unique ability to regenerate, allowing a healthy person to donate part of their liver to someone suffering from liver failure, and then both parts grow into two complete livers. 

UPMC is considered the leader in this type of transplant in America, having performed 89 operations in 2025. But even with this superiority, transplant recipients needed lifelong immunosuppressant drugs, because the immune system attacked the new organ as a foreign invader.

In 2017, the researchers launched their experiment on 13 patients. Weeks before the transplant, the team filtered white blood cells called "monocytes" from the donor's blood, then converted them into "regulatory dendritic cells". 

The function of these cells is to teach the recipient's immune system how to distinguish between harmful and friendly cells. These cells were then given to the recipient a week before surgery, to teach his immune system that the donor's liver is friendly and does not need to be attacked.

One year after transplantation, the participants underwent tests to determine if their immune systems were ready to be weaned off immunosuppressant drugs. Eight out of 13 patients were found to be eligible to begin tapering off the medication. Of these, four successfully discontinued the drugs completely, and three remained drug-free for more than three years. This means that the transplant tolerance rate among eligible patients was 37.5%, compared to only about 13% in patients not included in the trial.

The researchers caution that the results, while promising, are still exploratory and not conclusive. The trial was small and was not designed to prove definitive efficacy. 

The researchers now plan to conduct larger future trials, in which patients will be divided into two groups: one receiving regulatory dendritic cells and the other receiving standard care, to make a direct comparison. 

The team also suggests testing different immunosuppressant drugs that might be more suitable for these cells, administering the cells after surgery rather than before, and even considering obtaining the cells from deceased donors. Thompson emphasizes that they are looking to collaborate with other transplant centers to accelerate and expand their research.



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