Looking for Acute Liver Failure Biomarkers in Children
Acute liver failure (ALF) happens very quickly, with few warning signs before a child presents in the emergency room. But there are also few reliable predictors of a child’s outcome. That makes it challenging for physicians to know when it’s best to move forward with a liver transplant—and when it’s best to wait.
But what if specific biomarkers could better predict which children will recover on their own from acute liver failure—and which need lifesaving transplants?
Finding those biomarkers is the goal of a new research project led by Johanna Ascher Bartlett, MD, a Pediatric Gastroenterology fellow at Children’s Hospital Los Angeles. She recently received a Broad Clinical Research Fellowship Award from USC to support her study.
“We’re looking at 25 different immune cell markers to see if we can identify a predictive pattern that could indicate what the patient’s outcome would be in pediatric acute liver failure,” Dr. Ascher Bartlett explains. “If we could do that, we could potentially save some patients from transplants and immunosuppression, while more effectively identifying those children who truly must have a transplant to live.”
Targeting lymphocytes
To assist in this search, the team is turning to imaging mass cytometry (IMC), an advanced technology that allows investigators to examine up to 40 different proteins in a single cell—all at the same time—from just one tiny section of tissue.
The work is a collaboration with the Single Cell, Sequencing, and CyTOF Core at Children’s Hospital Los Angeles, which is led by Shahab Asgharzadeh, MD, and Jeffrey Bender, MD.
“Using IMC and CyTOF, we can look at what the cell populations are, profile them, quantify them and spatially map them,” Dr. Ascher Bartlett says. “We’ll then be able to use data modeling and data analysis to explore the different relationships between those cell types.”
Specifically, the team is using liver biopsies from patients with ALF to study certain subsets of lymphocytes, a type of white blood cell that’s important in immune response, as well as other mononuclear cells and antibodies.
“The most common type of acute liver failure in children is indeterminate; we don’t know what causes it,” she says. “But recent research has proposed that perhaps a subtype of that indeterminate acute liver failure is actually immune-mediated, with CD8 dense marking on the liver biopsy.
“What we’re theorizing is that, in some forms of acute liver failure, the lymphocytes are revved up and working against something,” she explains. “Through this research, we will be able to come up with a much more detailed characterization of that immune response.”
In addition to guiding treatment decisions, that more detailed understanding could potentially reveal targets for immunotherapy or other novel treatments for pediatric ALF. Right now, 41% of all patients end up having a liver transplant.
A huge potential impact
Having access to state-of-the-art technology—as well as the hospital’s large cohort of ALF patients—are just two advantages of doing this research at Children’s Hospital Los Angeles, Dr. Ascher Bartlett notes.
She is also benefiting from tremendous mentorship—working under liver transplant surgeon-scientist Juliet Emamaullee, MD, PhD, and Rohit Kohli, MBBS, MS, Chief of the Division of Gastroenterology, Hepatology and Nutrition.
“It’s a fantastic learning opportunity for me,” she says. “But I think what’s most exciting is the potential patient impact. If we are able to identify these biomarkers, the impact on pediatric liver transplant medicine could be transformative. I feel very fortunate to be a part of it.”
