Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging

AIM: To investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) in a group of obese children (BMI > 97th %) and to establish correlations between the severity of hepatic fatty infiltration, auxological findings and parameters of insulin resistance. METHODS: 44 obese children, aged 6-16 years, with a BMI above the 97th centile were selected for analysis. Hepatic fat content was assessed by phase contrast MRI. Demographic data included weight, height, body mass index, body fat mass and waist circumference. Blood tests included fasting blood glucose, fasting insulin and lipid profile. Insulin sensitivity was evaluated with QUICKI. RESULTS: Elevated hepatic fat fraction (FF) was identified in 14 subjects (31.8%; 0.07 SEM). Children with fatty liver (FF > 9%) had higher ALT (P<0.0001), AST (P=0.002) and triglycerides (P=0.008) values compared to the children without NAFLD. All the children showed a decreased insulin sensitivity (P<0.0001), but no difference was found between children with or without NAFLD. The degree of liver fatty infiltration was positively correlated with ALT (P<0.0001), AST (P<0.002) and gammaGT (P<0.0001), with height (P<0.006) and BMI (P<0.05) but not with estimates of body fat mass or fat distribution. CONCLUSION: Obese children are frequently affected by NAFLD, which cannot be predicted by clinical and/or anthropometrical findings. There is however a strict correlation between the degree of liver fatty infiltration and elevation of liver enzymes.     

The association between non-alcoholic fatty liver disease and insulin resistance in 20 obese children and adolescents

AIM: To investigate whether there are correlations between non-alcoholic fatty liver disease (NAFLD) and insulin resistance in obese children. For the first time, we present clinical data of 20 obese children with NAFLD, including an oral glucose tolerance test. METHODS: Twenty obese children were diagnosed as having NAFLD by abdominal ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (gamma-GT) were reported. Insulin sensitivity was evaluated by oral glucose tolerance test, oral glucose insulin sensitivity (OGIS) and homeostasis is model assessment (HOMA) index. All parameters were compared to 20 obese age- and sex-matched patients without NAFLD. RESULTS: With 81% the prevalence of insulin resistance according to HOMA or OGIS criteria was high in the NAFLD-patients compared to the other group with 63%. Statistically significant differences between both groups were found for mean serum ALT levels, mean glucose levels after 30, 60 and 90 minutes and mean insulin levels after 60 minutes of the glucose tolerance test. CONCLUSION: The high prevalence of insulin resistance we found in children with NAFLD confirms the suggestion that there may be an association between insulin resistance and NAFLD in obese children and indicates that markers of insulin sensitivity could be useful screening parameters for NAFLD.     

MRI and ultrasound for hepatic fat quantification:relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease

OBJECTIVE: The aims of this study were to evaluate hepatic steatosis severity in a series of obese children through both magnetic resonance imaging (MRI) and ultrasound, and to correlate imaging findings to clinical and metabolic characteristics of the study population. METHODS: Fifty obese children presenting hepatomegaly and/or elevated aminotransferases were candidates for assessment of hepatic fat fraction (HFF) by MRI. All subjects underwent dual energy X-ray absorptiometry scan measurement, and liver ultrasound scanning. Fasting blood samples were taken for the estimation of serum concentrations of glucose, insulin, leptin, aminotransferases and serum lipid profile. RESULTS: A diagnosis of fatty liver was established by MRI in 20 (40%) children; of these, 12 had HFF of 9-18%, while the remaining ones had HFF of 19% or higher. HFF was not correlated to age, SDS-BMI, pubertal status and fat mass. HFF was positively associated with serum concentrations of alanine aminotransferase (ALT; r=0.62; p<0.0001) and AST (r=0.39; p=0.006), as well as with insulin (r=0.44; p=0.001) and insulin resistance (r=0.49; p<0.0001). Overall, ultrasound correlated well with MRI (p<0.0001). However, HFF ranged greatly in subjects with moderate (2-37%) as well as with severe (11-25%) degree of ultrasound hepatic steatosis. In fact, the mean hepatic fat fraction in children with severe steatosis was not statistically different from that found in patients with moderate steatosis (p=0.98). In multiple regression analysis, the most powerful predictors of elevated ALT, after correction for age, gender, BMI and pubertal status, were insulin resistance (p<0.01) and MRI HFF (p<0.0001). CONCLUSIONS: Unlike sonography, an operator-dependent procedure, MRI is not subject to interpretation or inter-observer variation, and may be more useful than ultrasound for the monitoring of young patients with hepatic steatosis.     

Relationship of hepatic steatosis to adipose tissue distribution in pediatric nonalcoholic fatty liver disease

OBJECTIVE: Central adiposity, a component of insulin resistance syndrome, is a risk factor for nonalcoholic fatty liver disease (NAFLD) in adults. To determine whether a similar relationship occurs in children, hepatic fat content and adipose tissue distribution were assessed in obese children at risk for NAFLD. METHODS: We reviewed the charts of obese children undergoing evaluation for NAFLD because of hepatomegaly or elevated serum alanine aminotransferase (ALT) without obvious etiology. Hepatic fat fraction and adipose tissue distribution were obtained by rapid magnetic resonance imaging (MRI) techniques. Hepatic fat content was determined by a modification of the Dixon method that involves fast gradient echo. Body fat distribution was assessed by using heavily T1-weighted fast gradient echo technique on a single slice at the level of the umbilicus, and regions of interest were demarcated based upon pixel intensity threshold value including visceral adipose tissue (VAT) and subcutaneous adipose tissue content (SAT). RESULTS: Ten children underwent hepatic MRI only. Twenty-nine children underwent hepatic and adipose tissue distribution MRI. There was a correlation between hepatic fat fraction and VAT (r = 0.37, P < 0.05) but not body mass index or SAT. Elevated serum ALT was associated with a higher hepatic fat fraction (P < 0.001) and VAT (P = 0.06). CONCLUSION: Visceral adiposity is a risk factor for pediatric NAFLD.     

Decreased serum adiponectin: an early event in pediatric nonalcoholic fatty liver disease

OBJECTIVE: To evaluate the relative concentrations of cytokines in pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Thirty children were evaluated at a fasting morning visit to a pediatric research unit. RESULTS: Compared with normal-weight children (n = 12) and children who were overweight (n = 11), children who had presumed NAFLD (elevated Alanine aminotransferase [ALT] with negative work-up) (n = 7) had significantly lower mean serum adiponectin levels (P = .004). Adiponectin negatively correlated with body mass index (r = -0.60, P = .001), insulin (r = -0.74, P < .001), glucose (r = -0.52, P = .004), and ALT (r = -0.53, P = .003). There was no difference between normal-weight, obese, and presumed NAFLD subjects in mean serum tumor necrosis factor alpha and interleukin-6 and -8 concentrations nor in tumor necrosis factor alpha and interleukin-8 and -10 levels in an ex vivo lipopolysaccharide-stimulated system. CONCLUSIONS: Serum adiponectin is reduced in children with elevated ALT, similar to adults. However, children with presumed NAFLD do not have elevated pro-inflammatory cytokine levels. This suggests that depressed adiponectin plays a more proximal role than elevated levels of circulating pro-inflammatory cytokines in the development of NAFLD in children.     

Serum levels of soluble tumor necrosis factor-alpha receptor 2 are linked to insulin resistance and glucose intolerance in children

BACKGROUND: Obesity and insulin resistance are increasingly common problems in children. Tumor necrosis factor-alpha (TNF-alpha) has important effects on lipid and glucose metabolism. This effect may be mediated through soluble TNF-alpha receptor 2 (sTNFR2). OBJECTIVE: To investigate the relationship between insulin resistance and the TNF-alpha system in childhood obesity. CHILDREN AND METHODS: Twenty-one obese and six non-obese children were studied. Body mass index (BMI) z-scores, percent body fat (PBF) and waist to hip ratio (WHR) were determined. Fasting serum levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, TNF-alpha and sTNFR2 were measured. A standard 2-hour oral glucose tolerance test (dose of glucose: 1.75 g/kg, max. 75 g) was done. Insulin resistance (IR) was estimated by fasting plasma insulin, plasma insulin at 120 min, homeostasis model assessment (HOMA) and insulin area under the curve (AUC) from OGTT. Insulin sensitivity was estimated by oral glucose insulin sensitivity (OGIS120). RESULTS: Among the obese participants, one child (5.2%) was found to have diabetes mellitus and four others (21.1%) impaired glucose tolerance (IGT). Obese children had significantly elevated sTNFR2 levels. Furthermore, the group of obese children with IGT and the patient with newly diagnosed diabetes mellitus together (n = 5) had significantly higher levels of serum sTNFR2 (2,865+/-320 pg/ml) than the rest of the obese (2,460+/-352 pg/ml; p = 0.016) or lean (1,969+/-362 pg/ml; p = 0.014) children. Serum sTNFR2 levels correlated positively with insulin AUC, HOMA IR, fasting plasma insulin, plasma insulin at 120 min, total cholesterol and LDL/ HDL ratio, and negatively with OGIS120. Multiple regression analysis revealed that age, WHR, sTNFR2 and LDL predicted 81% of the variability in glucose at 120 min. CONCLUSION: sTNFR2 is a candidate marker of insulin resistance and glucose intolerance.     

瘦素/脂联素值与肥胖儿童体质量指数及糖脂代谢的关系

目的 探讨瘦素/脂联素(L/A)值与单纯性肥胖儿童体质量指数(BMI)、糖脂代谢及肥胖症发病的关系.方法 单纯性肥胖60例和57例健康儿童,采用放射免疫分析(RIA)法测定其血清瘦素水平;ELISA法测定其血清脂联素、空腹胰岛素(FINS)水平;免疫比浊法测定其血脂各成分.分析并比较血清瘦素、脂联素及L/A值与肥胖儿童BMI、糖脂代谢的相关性.结果 1.肥胖儿童血清瘦素、FINS和三酰甘油(TG)水平与健康对照组相比明显增加;脂联素水平降低,差异均有显著性(Pa＜0.05,0.01).2.单纯性肥胖儿童瘦素与BMI、FINS、TG水平均呈显著正相关(r=0.408,0.301,0.301 Pa＜0.05,＜0.01);脂联素水平与BMI、FINS、TG均呈显著负相关(r=-0.360,-0.413,-0.258 Pa＜0.01,＜0.05).3.L/A值与BMI、FINS、TG呈显著正相关(r=0.780,0.764,0.601 Pa＜0.001).结论 血清瘦素和脂联素与肥胖儿童的发病有关,可作为儿童肥胖的监控指标;L/A值较单独瘦素、脂联素更能反映肥胖症儿童的代谢状况,可为肥胖症儿童糖脂代谢提供更为有效的监测指标.     

肥胖儿童青少年血清脂肪因子与其代谢特征的相关性研究

目的 探讨肥胖儿童青少年血清脂肪因子瘦素、脂联素、神经调节蛋白4(Nrg4)及锌α-2糖蛋白(ZAG)与肥胖及代谢的关系。方法 选取在南京医科大学附属儿童医院儿童保健科就诊的5~14岁肥胖儿童。测量身高、体重、腰围、体脂百分比(FM%)、血压、腰围身高比(WHtR)和体重指数标准差(BMISDS);测定ALT、AST及糖脂代谢指标;根据血压及糖脂代谢,将肥胖儿童分为代谢不健康型肥胖(MUO)和代谢健康型肥胖(MHO)。酶联免疫吸附法测定血清脂肪因子水平。结果 192例肥胖儿童(男138名)纳入分析,平均年龄(10.59±1.93)岁,平均BMISDS 2.86(2.38,3.26)。肥胖儿童中检出MUO 164例(85.4%),MHO 28例。校正年龄后,MUO组血清脂联素、Nrg4水平低于MHO组(P<0.05),两组瘦素、ZAG差异无统计学意义。相关性分析显示,MUO组血清瘦素水平与 BMISDS、FM%、WHtR呈正相关(P<0.05);脂联素与年龄、ALT、AST及胰岛素抵抗指数(HOMA-IR)呈负相关(P<0.05);Nrg4与BMISDS、WHtR、ALT、AST呈负相关(P<0.05);ZAG与FM%呈负相关(P<0.05)。logistic回归分析显示,脂联素和Nrg4是肥胖儿童代谢保护因子;ROC曲线显示,脂联素与Nrg4评估肥胖儿童代谢风险的界值点分别为5.56 μg·mL^-1和5.5 ng·mL^-1。结论 肥胖合并代谢紊乱的儿童青少年血清瘦素、ZAG 水平与体脂含量密切相关,而脂联素、Nrg4水平与代谢紊乱程度相关。这些脂肪因子对于识别和干预肥胖儿童青少年代谢紊乱的发生发展具有重要意义。     

肥胖儿童青少年血清脂肪因子与其代谢特征的相关性研究

目的 探讨肥胖儿童青少年血清脂肪因子瘦素、脂联素、神经调节蛋白4(Nrg4)及锌α-2糖蛋白(ZAG)与肥胖及代谢的关系。方法 选取在南京医科大学附属儿童医院儿童保健科就诊的5~14岁肥胖儿童。测量身高、体重、腰围、体脂百分比(FM%)、血压、腰围身高比(WHtR)和体重指数标准差(BMISDS);测定ALT、AST及糖脂代谢指标;根据血压及糖脂代谢,将肥胖儿童分为代谢不健康型肥胖(MUO)和代谢健康型肥胖(MHO)。酶联免疫吸附法测定血清脂肪因子水平。结果 192例肥胖儿童(男138名)纳入分析,平均年龄(10.59±1.93)岁,平均BMISDS 2.86(2.38,3.26)。肥胖儿童中检出MUO 164例(85.4%),MHO 28例。校正年龄后,MUO组血清脂联素、Nrg4水平低于MHO组(P<0.05),两组瘦素、ZAG差异无统计学意义。相关性分析显示,MUO组血清瘦素水平与 BMISDS、FM%、WHtR呈正相关(P<0.05);脂联素与年龄、ALT、AST及胰岛素抵抗指数(HOMA-IR)呈负相关(P<0.05);Nrg4与BMISDS、WHtR、ALT、AST呈负相关(P<0.05);ZAG与FM%呈负相关(P<0.05)。logistic回归分析显示,脂联素和Nrg4是肥胖儿童代谢保护因子;ROC曲线显示,脂联素与Nrg4评估肥胖儿童代谢风险的界值点分别为5.56 μg·mL^-1和5.5 ng·mL^-1。结论 肥胖合并代谢紊乱的儿童青少年血清瘦素、ZAG 水平与体脂含量密切相关,而脂联素、Nrg4水平与代谢紊乱程度相关。这些脂肪因子对于识别和干预肥胖儿童青少年代谢紊乱的发生发展具有重要意义。     

肥胖症儿童血清抵抗素水平与胰岛素抵抗关系的研究

目的探讨肥胖症儿童血清抵抗素水平与高胰岛素血症和(或)胰岛素抵抗的关系。方法采用酶联免疫法测定34例肥胖儿童,31例正常对照的血清抵抗素水平。分析血清抵抗素与体重指数、体脂百分比、腰臀比及空腹血糖、空腹胰岛素水平、胰岛素抵抗指数、胰岛β细胞功能指数的相关关系。结果(1)肥胖组及对照组抵抗素浓度(对数转换值3.1±0.5)高于对照组(对数转换值2.7±0.8)(P<0.05)。(2)抵抗素与性别、年龄、收缩压、舒张压无相关关系;与体重指数、体脂百分比、腰臀比呈正相关(相关系数分别为r=0.299、0.304、0.322,P<0.01);与空腹血糖及空腹胰岛素水平呈正相关(相关系数为r=0.299和r=0.303,P<0.05);与胰岛素抵抗指数呈正相关(r=0.324,P<0.01),与胰岛β细胞功能指数无相关关系。(3)多元逐步回归分析表明,胰岛素抵抗指数为影响抵抗素最为显著的因素(R2=0.105);标准化偏回归系数0.279(P<0.01)。结论肥胖症儿童血清抵抗素水平较正常儿童增高,并与肥胖程度,脂肪分布密切相关。抵抗素可能与肥胖症儿童发生高胰岛素血症和(或)胰岛素抵抗有关。     

Changes in leptin, insulin and body composition in obese children during a weight reduction program

BACKGROUND: Girls have higher leptin concentrations than boys at all stages of biological development and this is also seen in the state of obesity. Little is known about whether gender and biological development of obese children influence changes in leptin associated with a short-term weight reduction program. OBJECTIVE: To study whether leptin concentration, body composition and insulin levels in obese children were influenced by a 3-week intervention program including diet and sports. STUDY DESIGN: Sixty-two obese children (32 boys and 30 girls) were examined before and after the intervention program. Body composition was measured by bioelectrical impedance and BMI-SDS was calculated. Serum leptin and serum insulin were determined by RIA. RESULTS: Girls had higher leptin levels than boys, before and after the weight reduction program. Body mass, fat mass (FM), leptin and insulin were decreased after the intervention in both sexes. We found a greater change in serum leptin in girls but the change in FM was of greater magnitude in boys. However, percentage changes in leptin were not significantly different between the sexes. Before the intervention, leptin concentrations were correlated with %FM, FM and moderately with BMI-SDS in all children. Only in pubertal boys did correlation of leptin with %FM increase after the intervention (from r=0.57 to r=0.75, p<0.01). Changes in leptin were found to be associated with initial leptin values in boys (r=0.95, p<0.01) and in girls (r=0.93, p<0.01), independent of Tanner stages. CONCLUSION: Serum leptin levels were positively correlated with adiposity in obese children and a diet and sports intervention program decreased serum leptin, insulin and body fat in all children. Changes in leptin were best described by the initial leptin concentration. The increase in correlation of leptin with %FM in obese pubertal boys after the intervention could have its underlying mechanism in an increased sensitivity to leptin and anabolic hormones.     

Insulin resistance and beta cell function in chronically transfused patients of thalassemia major

OBJECTIVE: To assess the glycometabolic function in chronically transfused patients of beta- thalassemia major in terms of glucose tolerance, insulin secretion, insulin resistance index, and beta cell function index and to determine their relationship with clinical and biochemical profile. METHODS: 30 homozygous thalassemia major children (aged 8-15 years) receiving regular blood transfusion and 10 age and sex matched normal children attending a tertiary level hospital were subjected to glucose tolerance test, estimation of fasting plasma insulin level, insulin resistance index and beta cell function index. Liver enzymes, liver size and indicators of iron overload (serum ferritin, total units of blood transfused, splenic size) were recorded. RESULTS: There was no diabetes mellitus or impaired glucose tolerance test in either the cases or the controls. Fasting plasma insulin levels were significantly higher in cases than controls (P = 0.004), and correlated well with indicators of iron overload like total units of blood transfused (r = 0.41, P = 0.03), serum ferritin (r = 0.38, P = 0.038) and splenic size (r = 0.43, P = 0.03). Insulin resistance was higher in cases compared to controls (P = 0.01). It correlated well with age (r = 0.56, P = 0.006), fasting blood glucose (r = 0.8, P = 0.003), fasting plasma insulin (r = 0.95, P = 0.00001), total units of blood transfused (r = 0.52, P = 0.005), serum ferritin (r = 0.4, P = 0.02) and splenomegaly (r = 0.51, P = 0.004). Insulin resistance was higher in patients not on chelation therapy compared with those on chelation therapy (P = 0.003). The beta cell function index was higher in cases compared to the controls, but not of statistic significance (P = 0.077). It did not correlate well with total amount of blood transfused (r = -0.32, P = 0.08), serum ferritin (r = -0.138, P = 0.46), spleen size (r = 0.16, P = 0.36), or chelation therapy (P = 0.98). CONCLUSION: Diabetes mellitus or impaired glucose was not seen in chronically transfused patients of thalassemia major (between 8 and 15 years of age), in our study. Insulin resistance, compensated by hyperinsulinemia, sets in early even before the onset of frank diabetes mellitus and correlated well with age, chelation therapy and indicators of iron overload like total units of blood transfused, splenomegaly and serum ferritin.     

Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease

OBJECTIVE: To examine the role of metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease. STUDY DESIGN: In 50 obese children (age 7 to 14 years) with (n = 20, group 1) or without (n = 30, group 2) hypertransaminasemia and ultrasonographic liver brightness, we studied insulin resistance (fasting glucose/insulin ratio [FGIR]) and serum levels of leptin, iron, transferrin, ferritin, C-reactive protein (CRP), white blood cell (WBC) count, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, C282Y and H63D mutations, and erythrocytic glutathione peroxidase (GPX) activity. RESULTS: FGIR (6.7 +/- 4.1 vs 9.2 +/- 5.2; P = .02), serum ferritin (88.8 +/- 36.0 vs 39.9 +/- 24.0 ng/mL; P = .0001), serum CRP (5.4 +/- 6.0 vs 1.1 +/- 1.6 mg/dL; P = 0.004), and GPX (8.4 +/- 0.9 vs 5.0 +/- 0.5 U/g Hb; P = .05) were significantly higher and more frequently deranged in group 1 than in group 2. FGIR, ferritin, and CRP values were simultaneously deranged in 41% of the group 1 patients and in none of the group 2 patients ( P = .098). Serum leptin, iron, and transferrin, WBC, TNF-alpha, IL-6, and C282Y and H63D mutations were similar in the 2 groups. CONCLUSIONS: Insulin resistance, oxidative stress, and low-grade systemic inflammatory status are implicated in pediatric obesity-related liver disease. These findings may be useful in planning pathophysiologically based therapeutic trials for hepatopathic obese children who are unable to follow hypocaloric diets.     

Relationship between insulin resistance and serum levels of adiponectin and resistin with childhood obesity

OBJECTIVE: The aim is to study the relationship between insulin resistance and serum adiponectin and resistin in obese children. METHODS: A total 113 obese and 37 nonobese children were enrolled and serum adiponectin and resistin were measured. RESULTS: Compared with controls, higher insulin resistance by homeostasis model (HOMA-IR) and lower whole body insulin resistance index (WBISI)were found in obese children (all P <0.05). The adiponectin levels in obese children and controls were 3.63 and 5.79 microg/L with a significant difference (P<0.001) while the difference of resistin levels was not significant (P = 0.948). Significant correlations between insulin resistance parameter and age,sexual development, BMI, serum triglyceride, ApoB, LDL-cholesterol, HDL-cholesterol, alanine aminotransferase, uric acid, or adiponectin levels (all P <0.05) were noted. Stepwise multiple regression analysis showed that BMI and adiponectin levels were independent determinants of WBISI. CONCLUSIONS: These results suggest that adiponectin may play a protective role in obese children through decreasing insulin resistance.     

CD40-CD40L系统与儿童肥胖的相关性

目的 探讨CD40-CD40L系统与儿童肥胖的相关性。方法 选取肥胖儿童76例为肥胖组，同时选取体重指数（BMI）正常的74例儿童为对照组。比较两组儿童形态学指标和生化指标，以及血清CD40和CD40L水平，并采用偏相关分析和多元线性回归分析研究肥胖组儿童CD40和CD40L与其他临床指标的相关性。结果 肥胖组BMI、腰围/身高之比、收缩压、舒张压、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、尿酸、三酰甘油、载脂蛋白B、空腹血糖、空腹胰岛素、糖化血红蛋白、血小板计数、CD40L及平均颈动脉内膜中层厚度均高于对照组（P < 0.05），而高密度脂蛋白胆固醇和载脂蛋白A1均低于对照组（P < 0.05）。以年龄和性别为控制因素，偏相关分析显示，CD40L与身高、体重、BMI、舒张压、胆汁酸、甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白B及血小板计数呈正相关（P < 0.05）；CD40与腰围/身高之比和血小板计数呈正相关（P < 0.05）。多元线性回归分析显示，ALT、AST、总胆固醇、血小板计数是CD40L水平的独立影响因素（R²=0.266，P < 0.05）。结论 CD40-CD40L系统与肥胖及肥胖相关的血脂紊乱和高血压密切相关，CD40和CD40L可能成为代谢综合征早期预警的新指标，为相关慢性病的防治提供新思路。     

The spectrum of fatty liver in obese children and the relationship of serum aminotransferases to severity of steatosis

OBJECTIVES: Non-alcoholic fatty liver disease is an emerging diagnosis in the pediatric population. Previously, ultrasonography and serum aminotransferases have been used to estimate prevalence of the disorder. A lack of concordance has been noted between these two diagnostic tests. To better understand the spectrum of fatty liver in obese children and the relationship of serum aminotransferases to the severity of steatosis, hepatic MRI was used to quantitate fat content. METHODS: Twenty-two children, ages 6 to 18 years, with obesity (BMI > 95th percentile for age) and hepatomegaly (liver edge more than 2 cm below the right costal margin) underwent hepatic MRI for fat quantitation. Hepatic MRI was performed using a modification of the Dixon method that used a fast gradient echo sequence rather than traditional spin echo. Scan times were sufficiently brief to allow completion within a single breath hold. Serum aminotransferases were obtained within one month of MRI. RESULTS: Twenty-one of 22 subjects had an elevated hepatic fat fraction. Seven of 7 subjects with a fat fraction of < or =18% had a normal serum ALT. Twelve of 13 subjects with fat fraction of >18% had an elevated serum ALT. Hepatic fat fraction correlated with serum ALT but did not correlate with age, BMI, or serum AST. CONCLUSION: The spectrum of fatty liver is larger than detected by screening for abnormal serum aminotransferases alone. Abnormalities in serum ALT occur exclusively in more severe cases of fatty liver.     

单纯性肥胖患儿非酒精性脂肪肝病与胰岛素抵抗

目的探讨单纯性肥胖(肥胖)儿童发生非酒精性脂肪肝病(NAFLD)的情况及与胰岛素抵抗(IR)、血脂、体质量指数(BMI)、腰臀比(WHR)的关系。方法选择肥胖儿童90例,年龄2.5～14.3岁。其中NAFLD 24例(NAFLD组),无NAFLD 66例(无NAFLD组)。另选35例年龄、性别与其相匹配的健康儿童为健康对照组。清晨空腹测量其体质量、身高、腰围和臀围,计算BMI和WHR,同时静脉采血检测其血清胰岛素(FINS)、糖(FBG)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和ALT、AST等,计算稳态模型胰岛素抵抗指数(HOMA-IR=FINS×FBG/22.5),并做肝胆等部位超声检查。结果 NAFLD占肥胖儿童的26.67%;NAFLD组儿童BMI、WHR最高,其次为无NAFLD组,差异均有统计学意义(Pa<0.001);3组儿童FINS和HOMA-IR值差异均有统计学意义(Pa<0.001),NAFLD组最高,其次为无NAFLD组,均明显高于健康对照组,但FBG无明显差异;NAFLD组血清TG、LDL-C和TC水平明显高于无NAFLD组和健康对照组(Pa<0.01);HOMA-IR值与BMI、WHR、血TG、LDL-C呈正相关(r=0.402、0.256、0.239、0.180,P=0.000、0.004、0.008、0.046);BMI、WHR诊断NAFLD的受试者工作特征(ROC)曲线下面积分别为0.805和0.765(Pa=0.000)。结论肥胖儿童NAFLD的发生与IR,血TG、LDL-C、TC升高及BMI、WHR增高关系密切,BMI、WHR对儿童肥胖NAFLD具有一定的诊断价值。控制体质量,减少腰围,可减轻IR,阻止NAFLD的发生、发展。     

血清谷丙转氨酶与儿童超重、肥胖的关系

目的：探讨血清谷丙转氨酶（ALT）与儿童超重、肥胖的关系。方法：对年龄7～18岁的2889例正常儿童及702例超重、肥胖儿童的资料进行分析,测量身高、体重、腰围、血压,检测空腹血糖、血脂、ALT、胰岛素等生化指标,计算胰岛素抵抗指数。结果：男童ALT水平高于女童。随着体重指数（BMI）的增加,男女童正常组、超重组、肥胖组ALT水平均逐渐增加。ALT与BMI、腰围、甘油三酯、胰岛素抵抗指数等相关。在超重、肥胖儿童中,男童ALT升高组BMI、腰围、血压、甘油三酯、低密度脂蛋白、胰岛素抵抗指数均较ALT正常组高（P<0.05）;女童ALT升高组腰围、血压、胰岛素抵抗指数高于ALT正常组,而高密度脂蛋白降低（P<0.05）。结论：ALT与儿童超重、肥胖及其引起代谢异常如血脂异常、胰岛素抵抗相关。     

Liver dysfunction in paediatric obesity: a randomized, controlled trial of metformin

AIM: In a previous study we showed that metformin reduced BMI z-scores and fasting glucose and insulin concentrations, and increased whole body insulin sensitivity in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. We analyzed the data from this study to determine (a) if metformin reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations during the 6-month trial, and (b) if the response to pharmacotherapy varied along gender or ethnic lines. METHODS: The 6-month trial was randomized, double blinded and placebo controlled; a total of 14 metformin-treated (500 mg bid) and 15 placebo-treated subjects completed the study. There were no dietary restrictions. RESULTS: In obese adolescents fed ad libitum, metformin (a) prevented the rise in ALT concentrations that were observed in placebo-treated subjects at the 3 to 5 month time-points (p < 0.05); (b) reduced (p < 0.01) the percentage of all ALT values exceeding 40 U/L; and (c) caused a modest (10%) but statistically significant (p < 0.05) reduction in serum ALT in Caucasian subjects. Metformin had no effect on ALT levels or the ALT to AST ratio in the five African American adolescents enrolled in the study but reduced their fasting insulin concentrations from 26.1 to 19.5 muU/mL (p < 0.05). CONCLUSIONS: Our findings suggest that metformin might reduce the rates or severity of liver dysfunction in selected high-risk adolescents.     

Glutathione S-transferase Alpha 1-1 and aminotransferases in umbilical cord blood

Recent data suggest that levels of glutathione S-transferase Alpha 1-1 in umbilical cord plasma may be a good indicator of neonatal hepatocellular integrity. In order to fully understand the significance of this new marker we compared the values of glutathione S-transferase Alpha 1-1 (GSTA1-1) with that of the well known liver function markers alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in arterial and corresponding venous umbilical cord blood of 93 patients. In addition, in 49 of these patients maternal venous blood was also studied. Both arterial and venous umbilical cord GSTA1-1 and AST levels were significantly higher than corresponding maternal venous levels, whereas ALT levels were not. Arterial umbilical cord GSTA1-1 correlated significantly with the corresponding AST and ALT levels (R = 0.46, P < 0.0001 and R = 0.41, P < 0.0001, respectively). Arterial umbilical cord AST correlated significantly with corresponding ALT levels (R = 0.58, P < 0.0001). Arterial umbilical cord plasma GSTA1-1 levels were significantly lower in the cesarean delivery group as compared to the vaginal birth group, whereas no difference was noted for AST or ALT. Arterial umbilical cord AST and GSTA1-1 levels correlated significantly with base deficit (R = 0.29, P = 0.005; R = 0.29, P = 0.005, respectively), whereas ALT did not (R = 0.06, P = 0.54). Arterial umbilical cord AST, ALT, and GSTA1-1 levels correlated significantly with birthweight. In conclusion, GSTA1-1 levels as assessed in neonatal umbilical cord blood, being unrelated to maternal levels, seem to be a more sensitive marker for early neonatal hepatocellular integrity as compared to ALT or AST and even might detect impaired hepatocellular integrity due to the vaginal birth process. Umbilical cord GSTA1-1 may provide a valuable indicator of neonatal condition immediately after birth, the clinical relevance of which needs to be further established.