Mendoza Michael, Caltharp Shelley, Song Ming, Collin Lindsay, Konomi Juna V, McClain Craig J, Vos Miriam B
*Department Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition †Department of Pediatrics, Division of Pediatric Pathology, Emory University ‡Children's Healthcare of Atlanta at Egleston, Atlanta, GA §Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, KY.
J Pediatr Gastroenterol Nutr. 2017 Jul;65(1):89-92. doi: 10.1097/MPG.0000000000001571.
Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children.
This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS).
The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration.
In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.
动物模型及针对成人的研究表明，限制铜摄入会增加非酒精性脂肪性肝病（NAFLD）患者肝损伤的严重程度。但尚未在儿童中开展此类研究。我们旨在确定较低的组织铜含量是否与儿童NAFLD严重程度增加相关。
这是一项对接受肝活检（包括肝铜定量）的儿科患者的回顾性研究。主要结局指标是比较NAFLD患者与非NAFLD患者的肝铜浓度。次要结局指标是比较肝铜水平与脂肪变性、纤维化、小叶炎症、气球样变性及NAFLD活动评分（NAS）。
该研究分析纳入了150名儿科受试者（102名NAFLD患者和48名非NAFLD患者）。在对年龄、体重指数z评分、γ-谷氨酰转移酶（GGT）、丙氨酸氨基转移酶（ALT）和总胆红素进行校正后，NAFLD患者的肝铜水平低于非NAFLD患者（P = 0.005）。此外，随着脂肪变性严重程度增加，组织铜浓度降低（P < 0.001）。铜水平与纤维化程度、小叶炎症、门管区炎症或气球样变性无关。
在这一队列的儿科NAFLD患者中，我们观察到与非NAFLD受试者相比，NAFLD受试者的组织铜水平降低。此外，与单纯脂肪变性相比，在非酒精性脂肪性肝炎（该疾病的一种更严重形式）患者中组织铜水平更低。需要进一步研究来探索铜水平与NAFLD进展之间的关系。
