AUG. 12, 2009

Liver transplant team at Packard Children’s leading the nation

BY ERIN DIGITALE

Ila Chakravarthy was 6 months old last fall but weighed just 10 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, home of the busiest pediatric liver transplant team in the nation. The hospital’s team performed more liver transplants in 2008 than any other U.S. children’s hospital, and also did the largest number of surgeries in infants like Ila, who were younger than 1 year at transplant. The team’s success rate, measured by patient and graft survival, is nearly 100 percent. 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, who directs the program.

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, 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. Berquist and his colleagues monitor about 500 children who are being evaluated for, recovering from or living with a liver transplant. 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

Soon after Ila’s April 2008 birth, her parents Maya Nanjundaswamy and Srinivas Chakravarthy realized their daughter was sick. She had jaundice that didn’t go away, and other clues indicated something was awry with her digestion. Ila was diagnosed with a congenital defect called biliary atresia: Her bile duct, the tube that carries digestive juices from the liver to the small intestine, was missing. With nowhere to go, her bile attacked her healthy liver, causing liver failure. It’s the diagnosis that accounts for about half of pediatric liver transplants, Esquivel said.

Most children with the condition need a transplant by age 3. Ila was too sick to wait that long. The blood she began vomiting in 2008 was a sign that circulation to her sclerotic liver was gravely impaired, and her life was in danger.

Like all transplant patients, Ila and her family were evaluated in accordance with United Network for Organ Sharing policies to ensure she met the criteria for transplant and they could handle the long-term commitment of caring for a transplanted liver. Because Maya wanted to donate part of her liver and had compatible immune-system markers, Ila became one of the 5 to 10 percent of Packard patients who receive a living-donor liver transplant.

“The day I was matched, Ila’s nurse on duty and all of us were crying because we were so thrilled,” Maya said.

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 1 to 2 millimeters in diameter, for example. The Packard Children’s team is up to these challenges. “We’ll often take patients turned down by other centers,” said Debra Strichartz, RN, the program’s nurse manager.

Surgery and beyond

On Dec. 11, 2008, Ila 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.’”

In the operating room, Esquivel said, a newly transplanted liver often begins working “almost right away. Within a few minutes you start seeing bile.” Esquivel also relies on blood tests in the OR to make sure the organ is functioning well.

Post-transplant patients are followed carefully. They stay in the hospital for a week or two, then have frequent clinic visits to check their well-being and monitor the immune medications that keep the body from rejecting the new organ.

“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 piece of liver Maya donated will grow with Ila, and the organ will also regenerate in Maya’s body. The outlook for Ila’s future is excellent, said Esquivel. “These children are very resilient.”

Packard progress

In June 2009, Ila, a cheerful 14-month-old, accepted her first-ever spoonful of carrot juice from her mother. Her mom tilted the spoon, then burst out laughing.

“She’s making the funniest faces,” said Maya, watching Ila squinch up her features as she considered the new food. Though it’s a lot of work to keep Ila and her environment scrupulously clean for her first risky year with the transplanted liver, Maya and Srinivas are delighted with their girl, who has bright black eyes, an inquisitive manner and a smile that reveals two perfect baby teeth.

The Packard Children’s liver transplant team is making pioneering advances, as well. 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 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 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.

In the teen clinic, which convenes every two months, adolescents begin seeing care providers separately from their parents. They’re expected to meet age-appropriate milestones in understanding their diagnosis and health-care needs. They get to meet other teens with transplants, and their parents can meet and share concerns, too.

“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 otherwise.”

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu/.