Marzuillo Pierluigi, Del Giudice Emanuele Miraglia, Santoro Nicola
Pierluigi Marzuillo, Emanuele Miraglia del Giudice, Department of women and children and General and Specialized Surgery, Seconda Università degli Studi di Napoli, 80138 Naples, Italy.
World J Hepatol. 2014 Apr 27;6(4):217-25. doi: 10.4254/wjh.v6.i4.217.
One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease (NAFLD), which is the most common form of liver disease in children. NAFLD is defined by hepatic fat infiltration > 5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake, viral, autoimmune and drug-induced liver disease. It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, which, in turn, can evolve into cirrhosis and end stage liver disease. Obesity and insulin resistance are the main risk factors for pediatric NAFLD. In fact, NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome, prediabetes and type 2 diabetes mellitus (T2D). In particular, it has been clearly shown in obese youth that the prevalence of metabolic syndrome, pre-diabetes and type 2 diabetes increases with NAFLD severity progression. Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition. Recently, a non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene (PNPLA3), has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children. Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein. The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes, is aimed at acting upon specific targets involved in the pathogenesis. There are some therapeutic approaches that are being studied in children. This article reviews the current knowledge regarding the pediatric fatty liver disease, the new insights and the future directions.
儿童肥胖最常见的并发症之一是非酒精性脂肪性肝病（NAFLD），它是儿童中最常见的肝病形式。NAFLD的定义是经肝活检评估，肝细胞脂肪浸润>5%，且无过量饮酒、病毒性、自身免疫性和药物性肝病。它涵盖了从单纯性脂肪变性到非酒精性脂肪性肝炎等广泛的肝脏疾病，而非酒精性脂肪性肝炎又可能发展为肝硬化和终末期肝病。肥胖和胰岛素抵抗是儿童NAFLD的主要危险因素。事实上，NAFLD与胰岛素抵抗的临床特征密切相关，尤其是代谢综合征、糖尿病前期和2型糖尿病（T2D）。特别是，在肥胖青少年中已清楚表明，随着NAFLD严重程度的进展，代谢综合征、糖尿病前期和2型糖尿病的患病率会增加。并非所有肥胖患者都会发生NAFLD的证据表明，疾病进展可能取决于环境因素和遗传易感性之间的复杂相互作用。最近，一种非同义单核苷酸多态性（rs738409），其特征是在含patatin样磷脂酶结构域3基因（PNPLA3）的第148位氨基酸处由编码异亮氨酸的C突变为编码甲硫氨酸的G，已在多民族成人及儿童队列中与肝脂肪变性相关联。另一个与PNPLA3共同作用以传递肥胖青少年患脂肪肝易感性的重要多态性是葡萄糖激酶调节蛋白中的rs1260326多态性。对于对生活方式改变依从性差或无反应/部分反应的NAFLD儿童，药物治疗方法旨在作用于发病机制中涉及的特定靶点。目前有一些治疗方法正在儿童中进行研究。本文综述了关于儿童脂肪性肝病的现有知识、新见解和未来方向。
