by Children’s Hospital Los Angeles

Credit: Pixabay/CC0 Public Domain

A recent study led by Principal Investigator Michael Goran, Ph.D., and Rachel Schenker, MD, a Fellow in the Children’s Hospital Los Angeles Liver Transplant Program, has found a novel combination of plasma-based biomarkers that could potentially predict liver fibrosis—scarring due to long-term inflammation or damage—linked to metabolic dysfunction‐associated steatotic liver disease (MASLD), the most common pediatric liver disease in the U.S.

The study findings were published in the Journal of Pediatric Gastroenterology and Nutrition.

The combined presence of these biomarkers—a metabolite called dihydroxyacetone phosphate (DHAP), and an enzyme, alanine transaminase (ALT)—could flag early signs of liver fibrosis, particularly in Latino adolescents with obesity who are at elevated risk for MASLD.

Liver fibrosis is currently diagnosed by invasive biopsies or imaging.

“There is an urgent need for more accessible, noninvasive, and cheaper screening methods, particularly for high-risk populations such as Latino adolescents with obesity,” says Dr. Goran, Director of the Nutrition and Obesity Program, Saban Research Institute. “We want to identify this disease early while the liver damage of MASLD can still be reversed.”

When Latino adolescents can be at higher risk for MASLD

Between 10% and 15% of Latino adolescents and 30%–40% of all adolescents with obesity develop MASLD, compared to 5%–10% of the general adolescent population. This higher risk among Latino adolescents is due to high rates of obesity, which causes fat deposition and inflammation in the liver, as well as genetics—about 50% of people with Latino ethnicity have a genetic mutation that raises the risk for MASLD.

Prospecting in plasma

Using data and patient samples from the Healthy Eating through Reduction of Excess Sugar (HEROES) trial, a 12-week study of 93 Latino adolescents with obesity, the researchers analyzed blood serum plasma using metabolomics and DNA, and measured liver fat fraction and stiffness.

DHAP, a marker of triglyceride synthesis, was significantly associated with fibrosis. Independently, ALT—a nonspecific marker of liver inflammation—was equally associated. DHAP and ALT combined were better at predicting liver fibrosis in combination than either alone.

“The combination of ALT and DHAP holds significant promise as a potentially low‐cost, noninvasive screening tool for fibrosis in Latino adolescents with obesity,” says Dr. Schenker. “Future studies will need to investigate if this could be an effective screening tool for the entire population.”

Collaborators included Rohit Kohli, MBBS, MS, Chief, Division of Gastroenterology, Hepatology and Nutrition at CHLA. Cholsoon Jang, Ph.D., and Cuauhtemoc Ramirez, UCI School of Medicine analyzed the data; Hooman Allayee, Ph.D., Keck School of Medicine of USC; and Xueheng Zhao, Ph.D., and Kenneth Setchell, Ph.D., Cincinnati Children’s Hospital Medical Center conducted metabolomics for the study.

More information: Rachel B. Schenker et al, Dihydroxyacetone phosphate is a novel predictor of hepatic fibrosis in Latino adolescents with obesity, Journal of Pediatric Gastroenterology and Nutrition (2024). DOI: 10.1002/jpn3.12420

Provided by Children’s Hospital Los Angeles

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