Department of Research and Pediatrics, Nemours Children's Health, Jacksonville, Florida, USA.
Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):652-660. doi: 10.1002/jpn3.12312. Epub 2024 Jul 8.
Prevalence 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 liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD.
Thirteen 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. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated.
Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes.
Sixteen-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.
代谢功能障碍相关脂肪性肝病（MASLD），以前称为非酒精性脂肪性肝病（NAFLD），以及其更严重形式如代谢功能障碍相关脂肪性肝炎（MASH）的继发病变，在肥胖儿童中的发病率迅速上升。儿童 MASLD 的治疗方法仍缺乏有效性和可持续性。我们确定了 N-乙酰半胱氨酸（NAC）对肥胖症和活检证实的 MASLD 患儿氧化应激、炎症和胰岛素抵抗（IR）生物标志物、肝酶、肝脂肪分数（LFF）和肝硬度（LS）的治疗效果。
13 名儿童（n=13；年龄：13.6±2.8 岁；NAS 评分>2）接受了为期 16 周的 NAC（600 或 1200mg NAC/天）或安慰剂的双盲、安慰剂对照试验。测量包括 LFF（磁共振成像）、LS（超声弹性成像）和身体成分。还测量了红细胞谷胱甘肽（GSH）、肝酶、胰岛素、葡萄糖、脂联素、高敏 C 反应蛋白（hs-CRP）和白细胞介素 6（IL-6）。计算了胰岛素抵抗的稳态模型评估（HOMA-IR）。
16 周的 NAC 治疗改善了（基线调整后组间差异均<.05）炎症标志物（IL-6 和 hs-CRP）、氧化应激（GSH）和 IR（HOMA-IR），并降低了肝酶、LFF 和 LS。体重和身体成分没有显示出有益的变化。
16 周的 NAC 治疗在肥胖症和 MASLD 儿童中耐受良好，并导致氧化应激、炎症和 IR 以及肝脏结局的改善。这项初步研究的结果支持进一步研究 NAC 作为 MASLD 儿童的治疗药物。
