The U.S. Food and Drug Administration (FDA) has approved the first clinical trial in the U.S. to use a genetically engineered pig liver to support patients with severe liver failure who don’t qualify for a transplant, according to an American Journal of Transplantation (AJT) report published in August.
“We’ve waited over two decades since the last trial of a bioartificial liver device,” says Dr. Robert Brown, Chief of the Division of Gastroenterology and Hepatology and a leading physician in transplant hepatology. “So, I’m excited to finally have another trial of an artificial liver support device and that the FDA seems to be more and more favorable to the idea that xenotransplantation [transplantation of living organs, tissues or cells from one species to another] may be a clinical reality during my career.”
This approval represents tremendous potential for the 35,000 U.S. patients hospitalized annually for liver failure. These patients often face limited treatment options and have high mortality rates.
As an alternative to liver transplantation, plasma exchange therapy may help survival but does not work for all patients. A pig liver used with a special extracorporeal liver (ECL) system could work as a bridge to keep patients alive while their own liver recovers. It works by physicians connecting the patient’s blood to the pig liver through an external machine.
The new clinical trial will enroll as many as 20 patients in U.S. hospitals. The patients must have acute-on-chronic liver failure and hepatic encephalopathy (a serious brain dysfunction caused by liver failure) and be ineligible for a transplant.
“Many of us feel this is overdue,” says Dr. Brown, adding that “the [benefit] of doing a perfusion instead of implantation is we can turn it off if there are clotting or other safety concerns.”
Dr. Brown explains that the fact that the livers are extracorporeal (occurring outside the living body) means that they can be disconnected from the circuit at a moment’s notice.
Dr. Brown added that even if transplantation of pig livers proves successful, there is still likely room for artificial liver devices. For example, pig livers could be best for patients who require more liver function over a short time or are not good medical candidates for a transplant, while patients who need less support for a more extended period may benefit more from the cellular solution.
“We are going to generate an enormous amount of data in a short amount of time,” says Dr Brown, who also recognizes the data may reveal the need to do further genetic modifications of the pigs.
“Future patients will benefit because I think this is the next step in order to learn what is necessary to entertain the idea of doing pig liver transplants,” says Dr. Brown.