Death Rate Escalates for Pediatric Liver Transplant Patients in ‘Growth Failure Gap’

1 in 6 Children Loses Priority Points Due to Flawed Score System, UCSF Study Shows

By Suzanne Leigh

Children waiting for new livers who are much smaller than their peers have a heightened risk of dying. Despite this, 40 percent of these undersized waitlisted children may lose vital points required to expedite transplantation, due to a ranking system that does not account for their growth failure.

A study of nearly 3,300 pediatric liver patients by researchers at UCSF Benioff Children’s Hospitals found that one in six patients who was waiting for a liver transplant fell into the “growth failure gap.” This means that despite their small size, they did not meet the definition of growth failure by the Pediatric End-Stage Liver Disease (PELD), a disease severity scoring system for children designed to improve organ allocation in transplantation. 

PELD allots seven points to infants with growth failure and six points to children under 12 with growth failure if their heights or weights fall below the 2.5th percentile for their age. These points are added to their overall score to expedite transplantation, since growth failure increases the risk of death both on the waitlist and post-transplantation. 

However, because the PELD calculations rely on height and weight thresholds that shift in three-month increments, smaller children at the older end of each quarter are at risk for not qualifying for these critical points, the researchers say. Findings were published in the American Journal of Transplantation on Dec. 19, 2019. 

Infants Waitlisted for Transplant at Highest Risk 

Emily Perito
Emily Perito, MD, senior author of the study. 

“What this means is that a baby who is days away from being 9 months of age will be compared to the 2.5th percentile weight and height of a 6-month-old. This infant may actually be below the cutoff for their current age, but due to PELD calculations, they will not be classified as having growth failure,” said senior author Emily Perito, MD, of the UCSF departments of pediatrics, and epidemiology and biostatistics, noting that babies are most vulnerable to falling into the growth failure gap, since they grow rapidly in the first months of life.

One in 10 infants and 1 in 20 children listed for liver transplantation in the United States dies on the waitlist, according to the United Network for Organ Sharing.

In the study, Perito and her colleagues identified patients in the growth failure gap by calculating their height and weight percentile at the exact age they were listed, rather than the three-month increments used by PELD, to determine whether their size was at or below the 2.5th percentile. 

The researchers wanted to see how the waitlisted children in the growth failure gap, who represented 40 percent of children with growth failure, compared with the waitlisted children with PELD-defined growth failure (26 percent of total), as well as those children without growth failure (57 percent of total).

They found that within six months on the waitlist, 24 of the 554 children in the growth failure gap had died (4.3 percent). This compares with 43 deaths (2.3 percent) for the 1,889 children without growth failure and 34 deaths (4 percent) for the 848 children with PELD-defined growth failure.

Risk for Growth Failure Gap Patients Continues Post-Transplant 

Within three years following transplantation, another 40 children in the growth failure gap had died (7.9 percent), versus 81 deaths (4.6 percent) of those without growth failure and 57 deaths (7.3 percent) in the PELD-defined growth failure group.

“We found that children in the growth-failure gap have the same life-threatening risks before and after transplantation as those patients who are classified as having growth failure,” said first author Sonja Swenson, a fourth-year medical student at UCSF. “This demonstrates that current PELD calculations are not an objective and measurable predictor of mortality.” 

Some 87 percent of pediatric liver transplant candidates have their waitlist priority determined by PELD.  However, almost half of these children (44 percent of total) rely on exception points on top of their calculated points, because PELD scores do not reflect the severity of their condition or their risk of waitlist death, said Perito. “The number of exception points that transplant centers appeal for is not standardized or objective, raising concerns about the fairness of this workaround,” she said.

PELD scores typically run to a maximum of 45 points, said Perito. In addition to growth failure, PELD factors in lab values for albumin, bilirubin and INR, which are key biomarkers of liver function.

“The six-to-seven-point increase in PELD that growth failure triggers is equivalent to the impact of large changes in PELD’s biochemical components,” she said. “The other labs would need to worsen from values indicating moderate disease to severe liver failure to achieve the same PELD increase.”