Liver Disorders Respond to 2 New Treatments
Two major advances in pediatrics may forever change the lives of newborns with transient jaundice and other children who suffer a rare but deadly condition that keeps bilirubin, the waste product that stains the skin yellow, dangerously high.
Surgeons at the University of Nebraska have been the first to do an experimental transplant of billions of liver cells in lieu of a whole organ, operating on a young girl with the rare condition called Criger-Najjar syndrome. Now the 11-year-old girl, Maria Louisa Lujan, back home in New Mexico, needs half the light therapy she once did--six hours a day instead of 12. And her bilirubin levels have never been so low, her father said.
“It was a hard decision to make, because the transplant had never been done before,” Michael Lujan said of his daughter’s surgery. Maria suffered a serious streptococcus infection three years ago that sent her bilirubin levels skyrocketing. “She was delirious for a week,” Lujan said. “Doctors told us she would need a liver transplant.”
Almost all newborns experience some yellowing of the skin, a minor annoyance caused by a buildup of bilirubin. It takes a few days or weeks for a bilirubin-excreting enzyme in the liver to kick in, and up to 10% of newborns must spend time under bright lights in the newborn nursery to reduce bilirubin levels. This light has been shown to shuttle bilirubin through the liver and out of the body.
In the rare case, children like Maria are born without the bilirubin-excreting enzyme, called glucuronyl transferase, and must spend their entire lives under such bright lights.
In many cases of Criger-Najjar, these high bilirubin levels destroy key brain regions. Many of these children never make it to adulthood because of brain damage.
The only way to replace the enzyme is through a liver transplant, researchers say.
At the same time that Maria was placed on the national organ transplant list, doctors in Nebraska were working on an idea to use hepatocytes--liver cells--instead of the entire organ. They had just received federal approval to perform the experimental surgery, and a child like Maria was a good candidate.
Results of the procedure were presented for the first time in Chicago at the recent American Assn. for the Study of Liver Diseases.
According to Dr. Ira Fox, the University of Nebraska School of Medicine surgeon who performed the transplant, he and his collaborators needed 7 billion liver cells--about 3% to 5% of the liver mass of a child Maria’s age--to get enough enzyme activity (12%) to make the transplant successful. It was expected to be a relatively simple procedure, merely infusing the cells into the main vein in the liver, he said.
Maria’s bilirubin levels were 26 milligrams per deciliter, dangerously high. Within days, the transplanted liver cells (from a donor organ) seemed to be working. Her bilirubin levels were between 10 and 14 milligrams per deciliter and have remained there for the last six months, Fox said.
There have been a few attempts at infusing liver cells into adults with acute liver failure. No one knows yet how successful these procedures will prove, Fox said.
He plans to bring Maria back in the summer for a second infusion. “We want to improve her life,” he said. “If she still has to be on phototherapy, she feels that nothing has changed. I think we can cure this disease with a second dose of cells.”
During the procedure, the patient was anesthetized for only as long as it took to place a catheter into the portal vein. Then the cells were transplanted through the catheter over a 15-hour period, during which the child was awake and active.
“This would be a great alternative to liver transplant,” Fox said. He still has no definitive proof that the liver cells are growing and functioning normally. The evidence suggests that it is working, he said.
“There are many exciting things happening in liver transplantation,” said Dr. Jayanta Roy-Chowdhury of Albert Einstein College of Medicine in New York City. Roy-Chowdhury and his wife, Namita, have developed a human-cell line that produces liver cells that they believe will be used for transplantation in the future.
In another major advance in pediatrics, researchers at Rockefeller University in New York City have developed a substance that they have tested on hundreds of newborns in Greece and Argentina. Administered in a single injection, it has eliminated the need for light therapy in virtually all babies with transient jaundice.
Rockefeller’s Dr. Attallah Kappas, who has spent the last decade studying babies in Greece, recently returned from that country armed with sheets of statistics that would make any researcher proud. The medicine developed to prevent jaundice did the job in 600 newborns in Athens, and it’s only a matter of time before similar studies begin in the United States.
Kappas and his colleagues said the medicine can in one shot reduce the need for light therapy by 75% in newborns with transient jaundice. And they are working on strengthening the formula of the substance, called tin mesoporphyrin, so that it might work for those with Criger-Najjar syndrome.
“We are very excited,” Kappas said of the findings, which were presented at scientific meetings over the last few months. The medicine inhibits bilirubin for about one week, long enough for the baby’s enzyme system to begin doing its lifelong job. “It’s been superbly successful. We are trying to extend its effect for Criger-Najjar patients.”
During one experimental study, he provided the substance to two teenagers with Criger-Najjar who lived at the Rockefeller hospital for 400 days. “There was no progression of the disease,” Kappas said.
Although light therapy has been used routinely in newborn nurseries since 1968 with no side effects, such a prevention could ultimately allow babies to go home sooner and cut health care costs, doctors say.
“This medication will transform the problem of phototherapy,” Kappas said. He has developed several products, but tin mesoporphyrin, he said, “is the only compound that has all the right properties.”
Kappas and his colleagues--Dr. Timos Valaes, a professor at Tufts University and Dr. George Martinez, a physician in Argentina--have studied the compound for five years “with no consequences of any kind,” Kappas said. “This is about as safe as one could ask for.”
