Effect of N‐acetyl cysteine in children with metabolic dysfunction‐associated steatotic liver disease—A pilot study

Abstract

BackgroundPrevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction‐associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N‐acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and (LS) in children with obesity and biopsy‐confirmed MASLD.MethodsThirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double‐blind, placebo‐controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high‐sensitivity c‐reactive protein (hs‐CRP), and interleukin‐6 (IL‐6) were also measured. HOMA‐IR was calculated.ResultsSixteen‐week NAC treatment improved (baseline adjusted between‐group p < .05 for all) markers of inflammation (IL‐6 and hs‐CRP), oxidative stress (GSH), and insulin resistance (HOMA‐IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes.ConclusionsSixteen‐week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD.