Children with liver disease face dramatically higher risk of early death

(Press-News.org) Researchers from University of California San Diego have found that children diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) are at significantly increased risk of premature death and serious long-term health complications. The findings, published April 22, 2025 in Hepatology, the scientific journal of the American Association for the Study of Liver Diseases, come from the Longitudinal InVestigation Evaluating Results of Steatosis (LIVERS) study, which followed 1,096 children over an average of 8.5 years. Nearly half of all deaths in the cohort were liver-related, and the overall mortality rate was 40 times higher than that of similar peers in the general U.S. population.

“Every child or young adult who died was a tragedy,” said Jeffrey Schwimmer, M.D., professor of pediatrics at UC San Diego School of Medicine and director of the Fatty Liver Clinic at Rady Children’s Hospital. “MASLD poses a real and measurable threat to pediatric health. To truly change outcomes, we need better tools to diagnose this disease, treatments that work for children, and systems that ensure every child has access to that care.”

MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in children, affecting nearly 10% of all youth and up to 25% of those with obesity. The reclassification to MASLD reflects growing recognition that fatty liver disease in children is closely linked to metabolic dysfunction, including obesity, hypertension and type 2 diabetes. Yet despite its prevalence, little has been known about the long-term risks it poses to children.

The LIVERS study is the most comprehensive assessment to date of clinical outcomes in pediatric MASLD. Conducted at Rady Children’s Hospital, the retrospective cohort study used medical records and National Death Index data to follow children ages 2 to 18 who were diagnosed with MASLD between 2000 and 2017. Over an average of 8.5 years of follow-up, 3.4% of children had died — a mortality rate more than 40 times higher than expected based on national averages and more than 50 times higher than expected based on state averages. These mortality rates are far higher than what has been reported in children with obesity or type 2 diabetes alone, suggesting that MASLD may confer independent risk beyond associated metabolic conditions.

The risk of death was higher in certain children, especially boys and those with low levels of high-density lipoprotein (HDL), often called the “good” cholesterol. Nearly half of the deaths were caused by liver disease itself, while others were due to heart-related conditions, accidents or suicide.

In addition to the risk of early death, many children in the study developed serious health problems while still in their teens or twenties. These included high blood pressure (14%), obstructive sleep apnea (9.5%) and type 2 diabetes (7.3%). Problems with blood fats, such as high triglycerides or low HDL, were even more common — making dyslipidemia, the presence of abnormal levels of fats (lipids) in the blood, the most frequent complication overall.

While many children showed improvement with clinical care, a substantial portion still experienced disease progression. The findings highlight how much we have yet to learn about the natural course of MASLD in children and reinforce the need for better tools to detect, monitor and manage this condition.

“We have shown that MASLD in children is a serious disease with life-threatening potential,” Schwimmer said. “Our hope is that these findings lead to greater awareness and stronger investment in pediatric-specific diagnostics, treatments and systems of care. With the right tools and commitment, we can make a meaningful difference in outcomes.”

Future research is needed to identify which children are at highest risk for progression to cirrhosis and early death, and to determine how lifestyle, medication or surgical interventions might change the disease course. For now, researchers emphasize that early recognition, consistent follow-up and greater public and provider awareness remain critical to protecting the health of children with MASLD.

Link to full study.

Additional co-authors on the study include: Nhat Quang N. Thai, M.P.H., Sheila L. Noon, Patricia Ugalde-Nicalo, M.D., Sabina R. Anderson, Lauren F. Chun, M.D., Nidhi P. Goyal, M.D., Kimberly P. Newton, M.D., Eleanor G. Hansen, M.D., Bonnie Lin, Warren L. Shapiro, M.D., Andrew Wang, D.O., Elizabeth L. Yu, M.D., Cynthia A. Behling, M.D., Ph.D. from UC San Diego; and Rhys S. David from Rady Children’s Hospital.

The study was funded, in part, by the National Institutes of Health (UL1TR001442), the Rady Children’s Hospital San Diego Physician Fund and a research grant from Intercept Pharmaceuticals.

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