Livers are so delicate that even the hardiest donor specimens fail if they aren't transplanted within 24 hours. But a fortuitous coincidence has led to the discovery that interferon (IFN) , a powerful anticancer drug, can double the lifetime of donor livers. The finding, reported in the November issue of Gastroenterology, could greatly improve the supply of donor livers and relieve some of the pressure on the complicated transplant procedure.
Fresh donor livers are immersed in a chilled solution of electrolytes and sugars to preserve their hepatocytes. These cells pump out as many as 5000 different proteins involved in everything from blood clotting to detoxification. But the near-freezing temperature quickly bloats the liver's sinusoidal cells, which cover the blood vessels. After transplantation, the bloated cells detach from the hepatocytes and die, weakening the blood vessels and starving the liver of blood.
Two years ago, researchers at Duke University Medical Center were investigating how to better preserve refrigerated livers. One team member at the time was also brushing up on breast cancer research after a relative had been diagnosed with the disease. According to Duke liver transplant surgeon Pierre-Alain Clavien, the team member noticed a "striking similarity" between the earliest stages of tumor development and injury to refrigerated livers. Liver sinusoidal cells were bloated exactly as their counterpart, endothelial cells, during angiogenesis, the growth of blood vessels to a tumor.
The team tested as liver preservatives three common anticancer drugs--fumagalin, minocycline, and IFN---that inhibit angiogenesis. They injected the drugs into rats before removing the animals' livers and into the extracted organs as well. IFN- was the only one to provide a "significant" improvement in the length of preservation of the sinusoidal cells, says Clavien. Because circulating IFN- levels peaked in the rats 2 to 6 hours after injection, he believes that a single dose given a few hours before an organ is removed from a rat--as well as adding the drug to the preservation solution--could make donor livers last perhaps 48 hours.
The new research offers a "unique perspective" on the process of liver damage, says Gregory Gores, a transplant hepatologist at the Mayo Clinic in Rochester, Minnesota. But the paper's implication--that the sinusoidal cells are trying to grow blood vessels, rather than simply dying--"is a hypothesis that needs to be proven." That proof, Gores suggests, lies in identifying the protein that triggers angiogenesis and looking for it in livers.