UPMC Children’s GI Division Begins Participation in TRIUMPH Trial for Acute Liver Failure
August 16, 2022
UPMC Children’s Hospital of Pittsburgh Division of Gastroenterology, Hepatology and Nutrition became an active site in July 2022 for the Treatment for ImmUne Mediated PathopHysiolgy (TRIUMPH) multicenter clinical trial that is investigating treatment options for pediatric acute liver failure (PALF).
James Squires, MD, MS, associate director of Hepatology and the program director for the Advanced/Transplant Hepatology Fellowship at the University of Pittsburgh School of Medicine, is the site principal investigator for the trial.
Simon P. Horslen, MBChB, FRCPCH, director of Pediatric Hepatology at UPMC Children’s, was instrumental in helping to develop the study as a co-leader of The Pediatric Acute Liver Failure Immune Response Network prior to joining UPMC Children's in 2021 will remain involved with the clinical trial at the national level.
About The TRIUMPH Study
While pediatric acute liver failure is rare, it often leads to high mortality levels or the need for a life-saving liver transplantation. Roughly one-third of documented cases of PALF are idiopathic, and treatment options for the failing liver have yet to progress beyond supportive care measures, or in the event of total liver failure, transplantation.
The rarity of the condition and the ongoing lack of understanding as to specific causative circumstances in these cases has made it exceedingly difficult for researchers to create any robust animal models of the disorder that can replicate the nature of the liver injuries observed in these cases of PALF.
However, evidence is mounting in these cases of idiopathic PALF that point toward the role of immune system dysregulation through aberrant T-cell responses to either common childhood infections or environmental exposures to unknown agents.
“The hypothesis that we are working under, and for which there is increasing evidence, is that there is an uncontrolled inflammatory response in the liver precipitating acute liver failure. The cause of this inflammatory response is not known but may be an aberrant response to common childhood infections,” says Dr. Horslen.
As Dr. Horslen explains, however, empiric use of methylprednisolone and ATG in some cases has been suggestive of these agents’ ability to blunt the dysregulated immune response, thereby giving the liver time to recover function.
Dr. Horslen also notes that equine ATG has a long track record of effective use in cases of aplastic anemia, a condition in which researchers believe there is a similar mechanism of injury as occurs in idiopathic acute liver failure in children; in fact, aplastic anemia may accompany the liver injury in a proportion of cases of PALF.
The TRIUMPH study will be the first investigation to test the use of methylprednisolone and eATG in pediatric patients to determine their efficacy and safety in treating PALF.
The three-arm study will compare the use of methylprednisolone and eATG against placebo in a cohort of 160 (target enrollment figure) pediatric patients with acute liver failure of undetermined etiology.
“With the mounting evidence for the critical role of the immune system’s response in these cases of PALF with no clear cause, we are excited to begin enrolling patients in the trial to see if either of these agents can lead to improvements in treatment and outcomes,” says Dr. Squires. “Any positive effects on liver failure outcomes or avoiding the need for transplantations will be of the utmost significance for these young patients and their families,” says Dr. Squires.
For patient referrals for further information about the trial at UPMC Children’s, please contact Dr. Squires at james.squires2@chp.edu.
Learn more about the Pediatric Acute Liver Failure Immune Response Network.
Read the full study protocol at ClinicalTrials.gov.
NASPGHAN 2022 Note
At NASPGHAN 2022, Dr. Squires will give a lecture during the Postgraduate Course on Thursday, October 13 at 10:00 am on the subject of acute liver failure. His lecture will discuss aspects of PALF and also touch upon the future of the PALF clinical investigation described above.
