Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy.
Unit of Endocrinology and Diabetes, "Bambino Gesù" Children's Hospital, IRCCS (Instituto di Ricovero e Cura a Carattere Scientifico), Rome, Italy.
Am J Gastroenterol. 2017 Aug;112(8):1277-1286. doi: 10.1038/ajg.2017.140. Epub 2017 May 30.
Small for gestational age (SGA) is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the correlation of birthweight with the severity of liver damage in a large cohort of children with NAFLD.
Two hundred and eighty-eight consecutive Caucasian Italian overweight/obese children with biopsy-proven NAFLD were included in the study. We examined the relative association of each histological feature of NAFLD with metabolic alterations, insulin-resistance, I148M polymorphism in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, and birthweight relative to gestational age.
In the whole NAFLD cohort, 12.2% of patients were SGA, 62.8% appropriate for gestational age (AGA), and 25% large for gestational age (LGA). SGA children had a higher prevalence of severe steatosis (69%) and severe portal inflammation (14%) compared with the AGA and LGA groups. Notably, severe steatosis (>66%) was decreasing from SGA to AGA and LGA, whereas the prevalence of moderate steatosis (33-66%) was similar in three groups. The prevalence of type 1 NAFLD is higher in the LGA group with respect to the other two groups (25% vs.5.2% vs.9.4%), whereas the SGA group shows a higher prevalence of overlap type (85.8%) with respect to the LGA group (51.4%) but not compared with the AGA group (75%). At multivariable regression analysis, SGA at birth increased fourfold the likelihood of severe steatosis (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.43-10.9, P=0.008) and threefold the likelihood of NAFLD Activity Score (NAS)≥5 (OR 2.98, 95% CI 1.06-8.33, P=0.037) independently of homeostasis model assessment of insulin resistance and PNPLA3 genotype. The PNPLA3-CC wild-type genotype was the strongest independent predictor of the absence of significant fibrosis (OR 0.26, 95% CI 0.13-0.52, P=<0.001).
In children with NAFLD, the risk of severe steatosis is increased by SGA at birth, independent of and in addition to other powerful risk factors (insulin-resistance and I148M variant of the PNPLA3 gene).
小于胎龄儿（SGA）与非酒精性脂肪性肝病（NAFLD）的风险增加有关。我们的目的是在一个患有 NAFLD 的大样本儿童队列中，研究出生体重与肝损伤严重程度的相关性。
纳入 288 例经活检证实为 NAFLD 的连续意大利白种超重/肥胖儿童。我们研究了 NAFLD 的每个组织学特征与代谢改变、胰岛素抵抗、载脂蛋白 L1 样磷脂酶域包含蛋白 3（PNPLA3）基因 I148M 多态性以及与胎龄相关的出生体重之间的相对关联。
在整个 NAFLD 队列中，12.2%的患者为 SGA，62.8%为适当胎龄（AGA），25%为大于胎龄（LGA）。与 AGA 和 LGA 组相比，SGA 患儿严重脂肪变性（69%）和严重门脉炎症（14%）的发生率更高。值得注意的是，严重脂肪变性（>66%）从 SGA 到 AGA 和 LGA 逐渐减少，而中重度脂肪变性（33-66%）在三组中的发生率相似。与其他两组（5.2%比 9.4%）相比，LGA 组的 1 型 NAFLD 患病率更高，而 SGA 组与 LGA 组（85.8%比 51.4%）相比，重叠型（85.8%）的患病率更高，但与 AGA 组（75%）相比则无显著差异。多变量回归分析显示，出生时 SGA 使严重脂肪变性的可能性增加四倍（优势比（OR）4.0，95%置信区间（CI）1.43-10.9，P=0.008），使 NAFLD 活动评分（NAS）≥5 的可能性增加三倍（OR 2.98，95% CI 1.06-8.33，P=0.037），独立于胰岛素抵抗和 PNPLA3 基因型的稳态模型评估。PNPLA3-CC 野生型基因型是无显著纤维化的最强独立预测因子（OR 0.26，95% CI 0.13-0.52，P<0.001）。
在患有 NAFLD 的儿童中，出生时 SGA 增加了严重脂肪变性的风险，这独立于且除了其他强大的危险因素（胰岛素抵抗和 PNPLA3 基因的 I148M 变体）之外。
