How Technology and Physiology Are Making Sick Livers Transplantable

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Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disease that begins with excess fat accumulation in liver cells. Left unchecked, this can progress to a more advanced disease stage, called nonalcoholic steatohepatitis (NASH), that involves scarring and inflammation of the liver. There aren’t any approved therapies for NASH yet, which means for some people, the last resort may be a liver transplant.

Due to an increase in diseased livers over the past two decades, this also means that the organs that have been donated are often too sick to be transplanted: 1 in 3 livers from deceased donors are typically unusable and are discarded. This also causes a huge backlog of patients who are desperately waiting for a liver transplant. As of 2020, there were more than 25,000 people waiting for a liver transplant in the U.S. alone.

Given the long waitlist, there is a huge interest in making unhealthy donor livers healthy enough for transplantation. One method is preserving donated livers using a process called ex situ machine perfusion. During this process, a machine pumps blood, nutrients and oxygen through the liver—while it’s outside the body—to maintain normal physiological function. A paper published in Nature Biotechnology showed that a human liver was successfully transplanted after three days of ex situ machine perfusion. After one year, the person who received the transplant was healthy with no signs of organ rejection or injury. This highlights the potential of ex situ perfusion to increase liver availability. 

My colleagues and I are also developing strategies in our lab to maintain liver health on perfusion machines to make them viable for transplant. These strategies involve adjusting the blood flow to the liver and the amount of oxygen and nutrients the liver receives while it’s hooked up to the machine.

We are also developing medications that can be used to treat the liver while it’s on the machine. For example, in an attempt to reduce fat in the liver, certain therapies will reduce activities that increase fat accumulation, similar to a dimmer switch on a light bulb. These drugs may also have the potential to treat people with NAFLD before they need a transplant.

This exciting new area of study is an excellent example of how technology and physiology are merging to try to increase the pool of healthy livers available for transplant. This new line of research will not only help the thousands of people on the waitlist, but it also opens up new avenues of treatment for those living with liver disease. 

Rory Cunningham, PhD, is a former postdoctoral fellow at the National Cancer Institute and a scientist at the liver therapeutics company Ochre Bio. His research involves developing and phenotyping models of human liver perfusions.

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