The right kind of oil

An answer to a medical mystery: why does prolonged IV feeding damage the liver?

Children who cannot eat on their own because of intestinal failure must rely on parenteral nutrition (PN), an intravenous method of feeding. Unfortunately, long-term PN can cause life-threatening liver disease, especially in infants, for reasons that have been unknown. Many infants who develop this complication die within a year of diagnosis, unless they can be weaned off PN or receive a liver/small intestine transplant. In the July issue of Pediatrics, researchers at Children's Hospital Boston report saving two babies' lives – with one able to come off a liver-transplant list – simply by changing the type of fat used in the PN solution.

The story began in 2001 when, seeking to understand why PN was causing liver disease, surgeon Mark Puder, MD, surgical resident Jenna Garza, MD, and pharmacist Kathy Gura, PharmD, decided to conduct studies in mice. They found evidence that the fat used in standard PN solutions, called Intralipid®, was contributing to liver disease by causing fat to accumulate in the liver.

Made largely of soybean oil, Intralipid is high in omega-6 fatty acids that are known to have an inflammatory effect. Puder's team decided to substitute OmegavenTM, an IV fat mixture made from fish oil. Fish oil contains omega-3 fatty acids, which have been shown to prevent fat accumulation and have anti-inflammatory properties. As hoped, PN using Omegaven as the fat prevented fat accumulation and liver injury in the mice.

Surgeon Rusty Jennings, MD, who directs Children's Advanced Fetal Care Center, had heard of Puder's research and wanted to try Omegaven in one of his patients, a 5-month-old patient born with gastroschisis, a life-threatening congenital defect in which the intestines develop outside the body. The surgeons had only been able to save a small portion of the boy's bowel, so he was unable to feed normally and was put on standard PN. He soon developed such serious liver damage that Jennings placed him on a transplant list for a liver and small bowel. But his small size made the chances of finding a donor slim, so Jennings appealed to Puder to "save his baby."

Since Omegaven isn't approved for use in the U.S., Puder had to receive special permission, under a compassionate-use protocol, to use Omegaven rather than Intralipid in his PN solution. Within 8 weeks, the baby's laboratory tests normalized, and his liver function improved so much that he was removed from the liver transplant list. Puder later treated a second child, a premature baby whose bowel had ruptured; he too had complete resolution of liver disease.

To date, 21 patients at Children's have received Omegaven as the fat portion of their PN under FDA compassionate-use guidelines, and most have done well; 2 have died from unrelated causes. Now, Puder and colleagues plan a formal clinical trial aimed at preventing liver disease in PN recipients, and have received funding from the March of Dimes.

"Using a fat emulsion consisting solely of fish oils may enable liver toxicity to be treated or prevented entirely in children and adults who are dependent on parenteral nutrition," Puder says.

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The animal research and the costs of importing Omegaven were paid for by the hospital's Department of Surgery, the Garret Smith research foundation, and individual family donations.

Founded in 1869 as a 20-bed hospital for children, Children's Hospital Boston today is the nation's leading pediatric medical center, the largest provider of health care to Massachusetts children, and the primary pediatric teaching hospital of Harvard Medical School. In addition to 347 pediatric and adolescent inpatient beds and comprehensive outpatient programs, Children's houses the world's largest research enterprise based at a pediatric medical center, where its discoveries benefit both children and adults. More than 500 scientists, including eight members of the National Academy of Sciences, nine members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Children's research community. For more information about the hospital visit: http://www.childrenshospital.org.


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