Experts Recommend Medication for Pediatric MASLD Management
In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper. Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant
In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.
Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-4src years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.
The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told Medscape Medical News.
The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.
The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.
One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 3src% of children are being screened in their pediatrician’s office.”
The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.
Successful and Sustainable Weight Loss
Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.
Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.
In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.
Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.
The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.
GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.
For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.
Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.
Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.
Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.
In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.
More Research Needed
The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.
Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told Medscape Medical News.
Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.
Educating Clinicians on Early Identification
When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.
“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.
“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.
The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.
The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.