Johns Hopkins is able to research and apply the latest advances in transplantation to its medical care for patients. The transplant team has recently focused one of their areas of research investigations on the goal of increasing the donor organ pool. In particular, Dr. Zhao Li Sun, liver transplant researcher has been working to identify more effective use of a special donor liver categorized as the "steatotic liver."
The success of liver transplantation has created an increasing imbalance between organs available for transplantation and the number of patients in need of transplantation. The number of people who have agreed to donate their organs - either while they are living or after they have passed away - is far less than the number of people needing organ transplantation. Each year, several thousand people face serious medical complications, and even death while awaiting a liver transplant. The gap between number of donor livers available and the number of people on the waiting list is further complicated because 13 percent to 50 percent of the donor livers show signs of steatosis. (This is also commonly referred to as "fatty liver" or a condition where there is an excessive amount of lipids in the cells of the liver.)
How common is the presence of steatotic ("fatty") livers in the general population? "Although only about 11% of young people have steatosis, the prevalence exceeds 40% in people over 60 years of age," says Dr. Sun. Because of this, the transplant team’s ability to successfully use fatty livers for transplantation would significantly increase the organ pool. The hope is that in the future, it could increase the number of transplantable livers and shorten the time people are forced to wait on the transplant list.
More than three years ago, the Hopkins liver transplant team, including Dr. Sun, recognized the opportunity to address this problem. At that time, fatty livers were not commonly used in transplantation because prior experience showed that they would not perform well when transplanted. Dr. Sun and a team of Hopkins researchers wanted to see whether they could improve the fatty liver’s performance once transplanted.
These past years of research at Hopkins provided hope for the successful use of fatty livers. Hopkins scientists found that they could treat fatty livers with a special protein (called "IL-6"), and that by doing this, they could increase the blood flow and the liver function of the liver when transplanted. This special treatment has not yet been fully tested in humans.
It is common practice for transplant specialists to use livers that have levels of steatosis no greater than 30%. At levels higher than that, steatosis of the liver is still a risk factor for poor liver
performance.
Dr. Sun hopes to continue his research and uncover what exactly causes livers at higher levels of steatosis to perform differently from non-fatty livers. He recognizes that recent evidence suggests that there are different chemical reactions that occur within the cells of fatty versus non-fatty livers. Different types of cell death occur following the cold preservation time for the two types of donor livers. |  |
Also, evidence shows that strategies for improving regeneration in lean livers are not effective in the presence of fat deposits in liver cells. Thus, fatty livers not only poorly tolerate long periods of cold preservation time, but also develop different types of injury than those observed in lean organs. Dr. Sun seeks to define new insights into mechanisms of injury related to steatosis.
"Our long-term goal is to develop protective strategies for the safe use of steatotic liver allografts for transplantation. We first demonstrated that in vitro IL-6 treatment prevents mortality following fatty liver transplant in rats. Thus, we believe the regulation of IL-6 signal transduction pathways may be an appropriate target for improving of fatty liver graft function and improve outcomes following transplantation of steatotic liver allografts," says Dr. Sun.
Dr. Sun next seeks to define the mechanism of primary non-function following fatty liver transplantation and develop a novel therapeutic strategy for the safe use of fatty liver for
transplantation.
