1 HepatoMetabolic Diseases Unit.
Am J Respir Crit Care Med. 2014 Jan 1;189(1):66-76. doi: 10.1164/rccm.201307-1339OC.
Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS and intermittent hypoxia are associated with liver injury in pediatric NAFLD is unknown.
To assess the relationship of OSAS with liver injury in pediatric NAFLD.
Sixty-five consecutive children with biopsy-proven NAFLD (age, mean ± SD, 11.7 ± 2.1 yr; 58% boys; body mass index z score, 1.93 ± 0.61) underwent a clinical-biochemical assessment and a standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers of hepatocyte apoptosis (cytokeratin-18 fragments), and hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, and CD163, surface markers of leukocytes, T cells, and activated macrophage/Kupffer cells, respectively. OSAS was defined by an apnea/hypopnea index (AHI) greater than or equal to 1 event/h, and severe OSAS was defined by an AHI greater than or equal to 5 events/h.
Fifty-five percent of children with NAFLD had nonalcoholic steatohepatitis (NASH), and 34% had significant (stage F ≥ 2) fibrosis. OSAS affected 60% of children with NAFLD; the presence and severity of OSAS were associated with the presence of NASH (odds ratio, 4.89; 95% confidence interval, 3.08-5.98; P = 0.0001), significant fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23-7.42; P = 0.0001), and NAFLD activity score (β, 0.347; P = 0.029), independently of body mass index, abdominal adiposity, metabolic syndrome, and insulin resistance. This relationship held also in nonobese children with NAFLD. The duration of hemoglobin desaturation (Sa(O2) < 90%) correlated with increased intrahepatic leukocytes and activated macrophages/Kupffer cells and with circulating markers of hepatocyte apoptosis and fibrogenesis.
In pediatric NAFLD, OSAS is associated with biochemical, immunohistochemical, and histological features of NASH and fibrosis. The impact of hypoxemia correction on liver disease severity warrants evaluation in future trials.
阻塞性睡眠呼吸暂停综合征（OSAS）和非酒精性脂肪性肝病（NAFLD）在肥胖儿童中很常见。OSAS 和间歇性低氧是否与儿科 NAFLD 中的肝损伤有关尚不清楚。
评估 OSAS 与儿科 NAFLD 中肝损伤的关系。
65 例经活检证实的 NAFLD 连续患儿（年龄，均值±标准差，11.7±2.1 岁；58%为男性；体重指数 z 评分，1.93±0.61）接受了临床生化评估和标准多导睡眠图检查。测量胰岛素敏感性、循环促炎细胞因子、肝细胞凋亡（细胞角蛋白 18 片段）和肝纤维化（透明质酸）的标志物。通过免疫组化分别用 CD45、CD3 和 CD163 对肝内炎症浸润进行标记，这三种标志物分别代表白细胞、T 细胞和活化的巨噬细胞/枯否细胞的表面标记。OSAS 定义为呼吸暂停/低通气指数（AHI）大于或等于 1 次/小时，严重 OSAS 定义为 AHI 大于或等于 5 次/小时。
55%的 NAFLD 患儿患有非酒精性脂肪性肝炎（NASH），34%的患儿存在显著（F 期≥2 级）纤维化。60%的 NAFLD 患儿存在 OSAS；OSAS 的存在和严重程度与 NASH（比值比，4.89；95%置信区间，3.08-5.98；P=0.0001）、显著纤维化（比值比，5.91；95%置信区间，3.23-7.42；P=0.0001）和 NAFLD 活动评分（β，0.347；P=0.029）有关，与体重指数、腹部肥胖、代谢综合征和胰岛素抵抗无关。这种关系在非肥胖的 NAFLD 患儿中也成立。血红蛋白饱和度下降（Sa(O2)＜90%）的持续时间与肝内白细胞和活化的巨噬细胞/枯否细胞增多以及循环肝细胞凋亡和纤维化标志物有关。
在儿科 NAFLD 中，OSAS 与 NASH 和纤维化的生化、免疫组织化学和组织学特征有关。纠正低氧血症对肝疾病严重程度的影响值得在未来的试验中进行评估。
