Pediatric acute liver failure (PALF) is one of the most challenging conditions in pediatric gastroenterology. PALF has a rapid onset, leads to loss of liver function and typically occurs in previously healthy children. It’s rare and severe, affecting about 250 children per year in North America with an estimated 15% mortality rate and an additional 20-30% of patients requiring liver transplantation.
There are two major challenges in PALF care. First, there’s no standardized treatment protocol for patients who have indeterminate cause, which is more than half of PALF cases. These patients only receive supportive treatments to keep them stabilized in hopes they recover on their own or until they receive a liver transplant.
The second challenge is that all PALF patients, regardless of whether there is treatment available, need urgent and coordinated care from multiple disciplines to address their complex needs.
For several years, Norberto Rodriguez- Baez, M.D., Director of Pediatric Hepatology at Children’s Medical Center Plano, has been a major contributor to The Pediatric Acute Liver Failure Study Group (PALFSG) studying PALF’s natural course and possible etiologies. Recently, Children’s Health℠ joined PALF Immune Response Network (PALF IRN), which will start an NIH multi-center clinical trial to evaluate different treatment options for patients with PALF.
"We’re exploring new treatment opportunities that have the potential to shift the PALF treatment paradigm, and we’ve also developed a multidisciplinary care model that fosters real-time collaboration,” says Dr. Rodriguez-Baez, who also serves as Assistant Dean for Student Diversity and Inclusion and Professor at UT Southwestern.
TRIUMPH clinical trial: Finding treatments for the unmet need in PALF
Twenty of the highest-volume PALF sites in the U.S., including Children’s Health, are participating in the TReatment for ImmUne Mediated PathopHysiology (TRIUMPH) clinical trial with the goal of identifying effective treatments for patients with PALF of indeterminate cause. The Phase 2 study will evaluate two immunosuppressive agents, corticosteroids and antithymocyte globulin, versus supportive care only.
“TRIUMPH is based on the theory that an immune reactive process causes severe liver damage in these patients,” says Dr. Rodriguez-Baez, who is leading the TRIUMPH clinical trial at Children’s Health. “Our center, as well as other top centers, have observed that immunosuppressive agents help some PALF patients improve. We want to evaluate whether this improvement is a true effect of the treatments.”
TRIUMPH is the first double-blind, three-arm, randomized, placebo-controlled trial of these immunosuppressive agents.
“By the end of this study, we hope to have enough information to justify the use of either of these medications to reduce the need for transplantation and improve survival rates,” Dr. Rodriguez-Baez says.
The study is now enrolling and Children’s Health aims to enroll many participants in the trial.
Standardizing urgent, real-time multidisciplinary care
PALF patients present with a range of complex, life-threatening conditions, including coagulopathy, encephalopathy and multi-organ dysfunction, such as renal failure. Additionally, some patients will progress to end-stage liver failure and require transplantation, even if they have a known, treatable cause and receive treatment.
To address all these conditions, the Liver Injury and Failure Treatment (LIFT team) was created under the leadership of Amal Aqul, M.D., Director of Hepatology at Children’s Health Dallas and Associate Professor at UT Southwestern. The team includes hepatologists, hematologists, nephrologists, transplant surgeons and ICU providers.
“A streamlined multidisciplinary approach is critical to stabilize these patients while we attempt to identify a cause, try treatment if possible and begin the transplant evaluation process if the patient isn’t recovering,” says Dr. Aqul, who also serves as the Medical Director of Liver Transplant Program. “We’ve established a unique care model that enables all the necessary specialists to work as quickly and effectively as possible from the moment the patient arrives.”
The LIFT team developed full diagnostic and treatment guidelines on how to manage these patients. These guidelines were translated to an order set in Epic. When a PALF patient arrives at Children’s Health, the entire LIFT team receives an automated notification through Epic once the pre-established order set is opened.
“With this automated system, the LIFT team can view the chart, discuss the care and track progress, as well as guide providers who are caring for these patients on our specialized hepatology floor or ICU – all in a very efficient, standardized way,” Dr. Aqul says.
For example, nephrologists evaluate patients to provide the appropriate renal replacement therapy, which could be hemodialysis, continuous veno-venous hemofiltration, or molecular adsorbent recirculating system (MARS) therapy. Simultaneously, if patients aren’t recovering, transplant surgeons begin evaluating patients for transplant candidacy and expedite their listing for a compatible donor organ. Throughout the patient’s care, social workers, child life specialists and chaplains also help the patient and their family to navigate this challenging time.
“All of these disciplines are not only communicating in Epic, but we also round together so we can discuss the patient in real-time,” Dr. Aqul says. “Each of the specialties, in addition to fellows and advanced practice providers, provide input and determine next steps together.”
Why Children’s Health: Shaping the future of PALF care
The multidisciplinary care model and participation in the TRIUMPH clinical trial are part of a larger commitment to advance PALF care.
UT Southwestern pediatric hepatologists practicing at Children’s Health collaborate with other centers on a regular basis to discuss patient cases. The team has also had an active role in PALFSG since 2000 and regularly participates in multi-center registries tracking patient data.
“We’re one of the highest volume centers in the nation and we only see about 12 to 15 PALF patients per year,” Dr. Rodriguez-Baez says, “so it’s critical that we collaborate with other centers to share data and best practices to continue to better understand this disease process and how to best treat it. We’re committed to leading innovation alongside other top centers to improve PALF patient outcomes.”
Learn more about innovative hepatology care at Children’s Health.