The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD

Callen Conroy; Aurelia Radulescu; Suzanna L Attia; Nathan Shelman; James T Lee; Roberto Galuppo Monticelli; Sara Hall; Rohit Kohli; Samir Softic

doi:10.4103/sjg.sjg_428_23

The combined pioglitazone and topiramate therapy for management of pediatric patients with severe MASLD

Saudi J Gastroenterol. 2024 May 10. doi: 10.4103/sjg.sjg_428_23. Online ahead of print.

Authors

Callen Conroy¹, Aurelia Radulescu², Suzanna L Attia³, Nathan Shelman⁴, James T Lee⁵, Roberto Galuppo Monticelli⁶, Sara Hall⁷, Rohit Kohli⁸, Samir Softic^{3

9}

Affiliations

¹ University of Kentucky College of Medicine, Lexington, KY, USA.
² Department of Pediatrics, University of Kentucky College of Medicine and Kentucky Children's Hospital, Lexington, KY, USA.
³ Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine and Kentucky Children's Hospital, Lexington, Kentucky, USA.
⁴ Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, USA.
⁵ Abdominal and Emergency Radiology Divisions, Department of Radiology, University of Kentucky, Lexington, KY, USA.
⁶ Department of Radiology-Division of Vascular and Interventional Radiology, University of Kentucky, Lexington, KY, USA.
⁷ Department of Anesthesiology, University of Kentucky HealthCare, Lexington, KY, USA.
⁸ Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, California, USA.
⁹ Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

PMID: 38726916
DOI: 10.4103/sjg.sjg_428_23

Abstract

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.

Methods: Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy.

Results: Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment.

Conclusion: In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.