Children’s Hospital Los Angeles researchers develop clinical tool to predict whether children with acute liver failure will need transplant

Newswise – Approximately 50 children in the United States are awaiting transplants each year due to acute liver failure. Unlike children with chronic liver disease, otherwise healthy children may suddenly worsen if they develop acute liver failure. Although acute liver failure in children is associated with viral hepatitis and drug-induced liver injury, at least half of cases have no obvious trigger. When a child with acute liver failure is brought to the emergency room, the medical team may only have a short window of time to decide whether a transplant is needed.

“Unlike most other organs in the body, the liver has the potential to regenerate,” said Juliet Emamaullee, MD, PhD, FRCSC, FACS, a transplant surgeon at Children’s Hospital Los Angeles. “But you may not know if a patient will become seriously ill enough to need an emergency transplant, or if their liver has the potential to recover. “A liver transplant is a major surgery that, among other problems, requires them to take immunosuppressive drugs for life. “

New applications to reduce uncertainty

Now, a team led by Dr. Emmaullee, director of research in the Division of Abdominal Organ Transplantation, has developed the Children’s Hospital of Los Angeles Acute Liver Failure (CHALF) Score, a free web application that can be downloaded via smartphones. The CHALF score predicts whether children with acute liver failure will recover or should be referred to a transplant center. Dr. Emamaullee is the senior author of the study, which was published in the journal Transplantation.

Current decision support tools are not suitable for pediatric acute liver failure

Existing decision support tools, such as the King’s College Hospital Criteria (KCHC), Pediatric End-Stage Liver Disease (PELD) score, or Liver Injury Unit (aLIU) score, are not effective in children with acute liver failure. Developed for different purposes. KCHC is designed for adults, not children. The PELD score was created to measure chronic liver disease (not acute liver disease) in children, and aLIU is based on laboratory results at one point in time; neither of these tools accurately captures the instability of children with acute liver failure.

Doctors do not want to refer children for liver transplantation who can recover with medical treatment—about 70 percent of children with acute liver failure will recover while retaining their original liver. But up to 25% of patients require emergency transplantation. Predicting whether a specific child’s condition will worsen is critical because 10 to 15 percent of children with acute liver failure are likely to die if they become too ill for a transplant or do not receive an organ in time. “We’re always playing a guessing game,” said study co-author Rohit Kohli, MBBS, MS, chief of the Division of Gastroenterology, Hepatology and Nutrition at CHLA. “Of course, to be on the safe side, we tend to move the child as quickly as possible and prepare the child for the transplant. But a lot of times, the children will band together.”

Test whether the tool works

Dr. Emamaullee’s team developed the CHALF score by building a machine learning-based model and training it on common test results received in the emergency room or upon admission to 147 pediatric patients with acute liver failure treated by CHLA. Researchers categorized patients during their hospitalization based on demographics, diagnoses and laboratory results and used statistical methods to derive clinical tests and values ​​that best predicted the likelihood that a child would survive with his or her own liver or require a transplant to prevent Died from liver failure.

The team then validated their predictive model in 492 similar patients from the National Institutes of Health’s (NIH) multicenter Pediatric Acute Liver Failure Study Group (PALFSG). The model was able to predict patient outcomes with high accuracy (0.83), outperforming two other pediatric decision support tools (PELD and aLIU).

Using the output of the CHALF model, the team built an application called the CHALF score, which assesses liver failure risk on a scale of 5-60. Scores above 30 predict a worse outcome and prompt referral to a transplant center. A score below 30 means the patient is likely to survive with his or her liver.

Five out of five so far

The team has since used the CHALF score to evaluate five children at CHLA. “Every time, the actual results matched CHALF’s predictions,” said Dr. Kohli. “This is like a light in a very dark room. The emergency room team will be able to decide whether to transfer the child to a transplant center and then whether to put the child on the liver transplant list. This tool will help with both decisions. .”

Next, the team will collaborate with Beth Carter, MD, medical director of the Liver and Intestinal Transplant Program and CHLA principal investigator, on the NIH-funded Treatment of Immune-Mediated Pathophysiology (TRIUMPH) study, which aims to To test whether liver damage can be reversed in children with acute liver failure by treatment with immunosuppressants. “We wanted to see how well our score predicted outcomes in these patients,” Dr. Emaullee said. “Scoring that is predictive and reliable can really make a difference in how we care for patients in situations of clinical uncertainty.”

The CHLA team is sharing CHALF scores with medical teams around the world. “Because we have externally validated it with a large data set from a multicenter study, people can start using it now,” Dr. Emaullee said.

Study co-authors include Johanna Ascher Bartlett, MD, of CHLA and USC, Sarah Bangerth, MS, and Shannon Jordan, both of USC, Carly Weaver of CHLA, Sarah Barhouma, MHA, and Kambiz Etesami, MD, of USC.

This research was supported in part by National Cancer Institute K08CA245220.

About Children’s Hospital Los Angeles

Founded in 1901, Children’s Hospital Los Angeles is at the forefront of pediatric medicine and is the largest provider of children’s hospital care in California. Children’s Hospital is home to renowned experts across disciplines who work together to provide inclusive and compassionate care and drive advancements that set pediatric standards nationally and globally. Children’s Hospital Los Angeles provides the world’s best level of care to a truly diverse population of children. The hospital is consistently ranked in the top 10 nationally on U.S. News & World Report’s Best Children’s Hospitals Honor Roll, including No. 1 in California and No. 1 in the U.S. Pacific region. Children’s Hospital Los Angeles is on a hospital mission to create hope and build a healthy future. Children’s Hospital Los Angeles is one of the top 10 children’s hospitals funded by the National Institutes of Health. The Saban Institute at Children’s Hospital Los Angeles supports a full range of research, enabling doctors and scientists to translate discoveries into treatments and bring answers to families faster. The Pediatric Academic Medical Center is also one of the largest pediatrician training programs in the United States. CHLA’s commitment to combating food insecurity, strengthening health education and literacy, and introducing more people to health care careers exemplifies the hospital’s commitment to building strong communities. To learn more, follow CHLA on Facebook , Instagram , LinkedIn , YouTube Xformerly known as Twitter, and visit CHLA.org/blog.