Gawrieh Samer, Karns Rebekah, Kleiner David E, Olivier Michael, Jenkins Todd, Inge Thomas H, Chalasani Naga P, Xanthakos Stavra
Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital, Cincinnati, OH, USA.
Arch Clin Biomed Res. 2023;7(1):112-119. doi: 10.26502/acbr.50170323. Epub 2023 Feb 20.
To gain insights into the mechanisms underlying distinct nonalcoholic fatty liver disease (NAFLD) histological phenotypes between children and adults, we compared hepatic gene expression profiles associated with NAFLD phenotypes between the two age groups.
Histological characteristics of intra-operative liver biopsies from adolescents and adults undergoing bariatric surgery were assessed by the same pathologist using the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Hepatic gene expression was measured by microarray analysis. Transcriptomic signatures of histological phenotypes between the two groups were compared, with significance defined as p-value <0.05 and a fold change >1.5.
In 67 adolescents and 76 adults, distribution of histological phenotypes was: not-NAFLD (controls) 51% vs 39%, NAFL 39% vs 37%, and NASH 10% vs 24%, respectively. There were 279 differentially expressed genes in adolescents and 213 in adults with NAFLD vs controls. In adolescents, transcriptomes for NAFL vs controls, and borderline vs definite NASH were undifferentiable, whereas in adults, NAFL and borderline NASH demonstrated a transcriptomic gradient between controls and definite NASH. When applied to adolescents, significant adult genes discriminated borderline and definite NASH from control and NAFL, but the majority of significant pediatric genes were not portable to adults. Genes associated with NASH in adolescents and adults showed some ontological consistency but notable differences.
There is some similarity but major differences in the transcriptomic profiles associated with NAFLD between adolescents and adults with severe obesity. These data suggest different mechanisms contribute to the pathogenesis of NAFLD severity at different stages in life.
为深入了解儿童和成人非酒精性脂肪性肝病（NAFLD）不同组织学表型背后的机制，我们比较了两个年龄组中与NAFLD表型相关的肝脏基因表达谱。
同一位病理学家使用非酒精性脂肪性肝炎（NASH）临床研究网络评分系统，对接受减肥手术的青少年和成人术中肝脏活检的组织学特征进行评估。通过微阵列分析测量肝脏基因表达。比较两组之间组织学表型的转录组特征，显著性定义为p值<0.05且倍数变化>1.5。
在对67名青少年和76名成人的研究中，组织学表型分布分别为：非NAFLD（对照组）51%对39%，NAFL 39%对37%，NASH 10%对24%。与对照组相比，患有NAFLD的青少年中有279个差异表达基因，成人中有213个。在青少年中，NAFL与对照组以及临界与确诊NASH的转录组无法区分，而在成人中，NAFL和临界NASH在对照组和确诊NASH之间表现出转录组梯度。当应用于青少年时，显著的成人基因可区分临界和确诊NASH与对照组和NAFL，但大多数显著的儿童基因无法应用于成人。青少年和成人中与NASH相关的基因显示出一些本体一致性，但也存在显著差异。
重度肥胖的青少年和成人中，与NAFLD相关的转录组谱存在一些相似性，但也有主要差异。这些数据表明，不同机制在生命不同阶段导致NAFLD严重程度的发病机制中起作用。
