Liver transplantation performed in a six-month old infant

Ila Chakravarthy was six months old but weighed just ten pounds. Then, in October 2008, she began vomiting up big clots of blood, and the condition of her failing liver grew worse. The time had come, her doctors said. Though her size and fragile health would make surgery perilous, Ila urgently needed a liver transplant.

Ila and her worried parents were referred to Lucile Packard Children's Hospital at Stanford, home of the busiest pediatric liver transplant team in the nation. The hospital's team performed more liver transplants in 2008 – the most recent reporting period – than any other U.S. children's hospital, according to the United Network for Organ Sharing. They also did the largest number of surgeries in infants like Ila, who were younger than one year when they received a transplant. The team's success rate, measured by patient and graft survival, suggested that if anyone could save Ila, it was this team.

"We're known for taking care of very small children, transplanting much sicker patients, and treating more kids with cancer than any other institution in the country," said surgeon Carlos Esquivel, MD, PhD, chief of the division of transplantation.

Caring for the 45 children (including 18 infants) who got new livers at Packard last year required not just Esquivel's surgical acumen, but the expertise of dozens of medical professionals: hepatologists, nephrologists, gastroenterologists, anesthesiologists, physician assistants, social workers and nurses. The team prepares patients for surgery and provides years of crucial follow-up care. Their "bench-to-bedside" research gives patients innovative treatment options, such as kid-friendly immunosuppressive drugs, multi-organ transplants and a special clinic that helps teens take responsibility for their own care.

"When you’re doing a lot of transplants, especially difficult ones, you can get really successful at it and learn how to use your resources very effectively," said pediatric hepatologist William Berquist, MD. For patients who are transplanted as babies and followed at Packard through years of childhood and adolescence, he said, "we become like parents."

The Road to Transplant

Ila's liver began failing because of a congenital defect called biliary atresia – she lacked the tube connecting her liver and small intestine. Doctors told her parents, Maya Nanjundaswamy and Srinivas Chakravarthy, that Packard Children's had the expertise to perform a difficult transplant in a small infant like their daughter.

"We'll often take patients turned down by other centers," said Debra Strichartz, RN, the program's nurse manager.

The tiniest and sickest children, like Ila, need extra care at all stages of the transplant process. To make sure a child can handle surgery, the team's medical subspecialists concentrate on preparatory measures such as preventing infection, treating bleeding and maximizing nutrition. In the operating room, babies require extra surgical skill: the hepatic artery in an infant may be only one to two millimeters in diameter, for example.

Surgery and beyond

On Dec. 11, 2008, Ila finally received her lifesaving transplant. "What stays with me the most," Srinivas said, "is that after surgery, Dr. Esquivel told us, 'This was arguably the worst-looking liver I have seen in a kid that age in a long time.'"

"Soon after surgery, we see a transformation," Berquist said. Patients thrive and grow, making up for the slowed growth they experienced during liver failure. In "before" and "after" photos, Ila goes rapidly from scrawny and fragile to plump and grinning. "We had one Ila before transplant, and another after," Maya said. "Her disposition changed drastically – she's so much happier," added Srinivas.

The outlook for Ila's future is excellent: she's now an inquisitive toddler who grins toothily at her parents and is beginning to walk and talk. Says Esquivel, "These children are very resilient."

Packard Progress

The Packard Children's liver transplant team is making pioneering strides forward, too. They've performed multi-organ transplants of heart and liver, kidney and liver, and small intestine and liver. They have collaborated with pediatric oncology to obtain excellent results for children with liver cancer. And they are conducting extensive research on the best immunosuppressive regimen for young organ recipients.

"The success of transplant is such a fine line between infection and immune rejection," Esquivel said. With higher doses of immunosuppressive drugs, patients are more vulnerable to pathogens, and with too little medication, they risk graft rejection.

Thanks to Packard and Stanford research, young liver recipients are no longer given prednisone, a steroid drug that has serious side effects in children. Researchers at Packard Children's and the Stanford University School of Medicine are now trying to understand the molecular mechanisms of rejection. They hope ultimately to be able to induce immune tolerance to transplanted organs.

As Ila grows, she'll benefit from the liver team's innovative approach in the clinic, too. Packard Children's started the first "teen clinic" to help adolescent patients take charge of their own care. Berquist began the teen clinic in response to studies showing graft rejection rises in the teen years, perhaps because patients rebel by skipping doses of their immunosuppressive medication.

"We try to create very responsible patients," said Berquist. "We’re all excited to see the success of these children who've grown up to be adults, and who would have died without the work of our team and this very successful program."

http://www.lpch.org/