Hepatic Steatosis In Obese Children Research Articles

Associations of Adipocyte-derived Versican and Macrophage-derived Biglycan with Body Adipose Tissue and Hepatosteatosis in Obese Children

In animal models of obesity, adipocyte-derived versican, and macrophage-derived biglycan play a crucial role in mediating adipose tissue inflammation. The aim was to investigate levels of versican and biglycan in obese children and any potential association with body adipose tissue and hepatosteatosis. Serum levels of versican, biglycan, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were measured by ELISA. Fat deposition in the liver, spleen, and subcutaneous adipose tissue was calculated using the IDEAL-IQ sequences in magnetic resonance images. Bioimpedance analysis was performed using the Tanita BC 418 MA device. The study included 36 obese and 30 healthy children. The age of obese children was 13.6 (7.5-17.9) years, while the age of normal weight children was 13.0 (7.2-17.9) years (p=0.693). Serum levels of versican, hsCRP, and IL-6 were higher in the obese group (p=0.044, p=0.039, p=0.024, respectively), while no significant difference was found in biglycan levels between the groups. There was a positive correlation between versican, biglycan, hsCRP, and IL-6 (r=0.381 p=0.002, r=0.281 p=0.036, rho=0.426 p=0.001, r=0.424 p=0.001, rho=0.305 p=0.017, rho=0.748 p<0.001, respectively). Magnetic resonance imaging revealed higher segmental and global hepatic steatosis in obese children. There was no relationship between hepatic fat content and versican, biglycan, IL-6, and hsCRP. Versican, biglycan, hsCRP, and IL-6 were not predictive of hepatosteatosis. Body fat percentage >32% provided a predictive sensitivity of 81.8% and a specificity of 70.5% for hepatosteatosis [area under the curve (AUC): 0.819, p<0.001]. Similarly, a body mass index standard deviation score >1.75 yielded a predictive sensitivity of 81.8% and a specificity of 69.8% for predicting hepatosteatosis (AUC: 0.789, p<0.001). Obese children have higher levels of versican, hsCRP, and IL-6, and more fatty liver than their healthy peers.

Evaluation of metabolic score for insulin resistance index as a sensitive marker of insulin resistance and its ability to predict hepatic steatosis in obese children and adolescents. A pilot study

Evaluation of metabolic score for insulin resistance index as a sensitive marker of insulin resistance and its ability to predict hepatic steatosis in obese children and adolescents. A pilot study

Association of abdominal subcutaneous fat thickness with hepatic steatosis, liver enzymes, and serum lipids in obese children.

Childhood obesity can cause hyperlipidemia and hepatic steatosis at early age and chronic disease complications in adult life. We aimed to evaluate the relationship between abdominal subcutaneous fat thickness (ASFT) and hepatic steatosis, serum lipid and transaminase levels in obese children. A retrospective study was conducted with children (aged 4-18 years) who presented to outpatient clinic due to obesity. Associations between ASFT as assessed by ultrasonography (US) and hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and serum lipid profile were evaluated. We identified 95 children, all of which were diagnosed as having hepatic steatosis; the most common type was grade 1 (73.6 %, n: 70), followed by grade 2 (21.1 %) and grade 3 (5.3 %). The mean values of midline and flank ASFT were measured as 38.48 ± 11.53 mm and 20.91 ± 8.00 mm in grade 1; 41.23 ± 10.03 and 19.84 ± 6.75 in grade 2 and 63.12 ± 12.08 and 23.22 ± 5.92 in grade 3 hepatic steatosis, respectively. Midline and flank ASFT correlated positively with triglycerides in grade 3 steatosis, while midline ASFT correlated with body mass index, total cholesterol, low-density lipoprotein cholesterol, and AST (r: 0.9; p: 0.037; r: 0.648, p: 0.001; r: 0.387, p: 0.001; r: 0.406, p: 0.001, r: 0.463, p: 0.001; respectively) in grade 1 steatosis. ASFT as assessed by US may be of predictive value for hyperlipidemia in grade 3 and for hypercholesterolemia in grade 1 hepatic steatosis in obese children.

Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents

BackgroundNonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD. AimsWe examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors. MethodsWe recruited a cohort of 514 obese children and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system. ResultsThe overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2 rs58542926 (OR = 4.13, p = 0.002), GCKR rs1260326 (OR = 1.53, p = 0.003), PNPLA3 rs738409 (OR = 1.58, p = 0.004) and ELOVL2 rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75–0.88] vs. 0.77 [0.70–0.84] without SNPs; p = 0.047). ConclusionsNAFLD was strongly associated with three genetic variants, TM6SF2 rs58542926, PNPLA3 rs738409 and GCKR rs1260326, and more slightly with ELOVL2 rs2236212, in obese children and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.

Feasibility of balanced steady-state free precession sequence at 1.5T for the evaluation of hepatic steatosis in obese children and adolescents.

To determine the feasibility of balanced steady-state free precession (b-SSFP) imaging for measuring hepatic steatosis in obese children and adolescents, using proton magnetic resonance spectroscopy (1H MRS) as reference standard. 182 obese Chinese paediatric patients underwent conventional T1-weighted dual echo MRI, 1H MRS and b-SSFP imaging for non-invasive assessment of hepatic steatosis. There was a strong positive correlation between liver fat fraction (FF) on T1-weighted dual echo MRI and 1H MRS-determined liver fat content (LFC) (r = 0.964, p < .001), and a strong negative correlation between the ratio of liver signal intensity (SI) to spleen SI (L/S) on b-SSFP and LFC (r = -0.896, p < .001). ROC curve analysis based on a diagnostic threshold of 1H MRS-determined LFC >50 mg/g (>5 % by wet weight) showed areas under the curves for FF and L/S at 0.989 (0.976-1.000) and 0.926 (0.888-0.964), respectively. Optimal FF and L/S cut-off values identified patients with hepatic steatosis with 97.9 % and 86.5 % sensitivity and 93.4 % and 93.4 % specificity, respectively. Following further validation, b-SSFP at 1.5T has potential as a feasible technique for evaluation of hepatic steatosis in obese paediatric patients with limited breath-holding capacity. • L/S on b-SSFP images closely correlated with 1 H MRS-determined LFC. • b-SSFP has high diagnostic accuracy for hepatic steatosis in obese children. • 100% of obese paediatric subjects are imaged successfully using b-SSFP sequence. • b-SSFP has potential to evaluate hepatic steatosis in children with poor breath-hold.

Individual fatty acids in erythrocyte membranes are associated with several features of the metabolic syndrome in obese children.

Obesity leads to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) also in children and is often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been proposed as beneficial in this setting. The aim of the study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA, markers of average intake, in a group of 70 overweight/obese children. We conducted an observational study. Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation coefficients (rS) were calculated to evaluate associations between FA and features of the MetS. Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = - 0.352), triglycerides (rS = - 0.379), fasting insulin (rS = - 0.337) and 24-h SBP (rS = - 0.313). Total amount of saturated FA (SFA) and specifically palmitic acid, correlated positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was positively correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = - 0.472). Our data suggest that omega-6 FA, and especially AA, could be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.

OP.5C.09] OMEGA-6 FATTY ACIDS IN ERYTHROCYTE MEMBRANE ARE INVERSELY ASSOCIATED WITH SEVERAL FEATURES OF THE METABOLIC SYNDROME IN A GROUP OF OBESE CHILDREN

Objective: Overweight and obesity lead to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) not only in adults but also in children and are often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and in particular omega-3 fatty acids (FA) have been proposed as beneficial. Design and method: The aim of this observational study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA (by gas-chromatography), markers of average intake, in a group of obese children. Results: We enrolled 70 children (BMI = 29.4 ± 4.4 Kg/m2; percentile of BMI = 98.0 ± 1.7), aged 5–17 years. Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Omega-3 FA were not associated with MetS characteristics, whereas omega-6 FA, in particular arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = −0.352), waist/hip ratio (rS = −0.311), Waist/height ratio (rS = −0.248), triglycerides (rS = −0.366), fasting insulin (rS = −0.337), 24-hour-SBP (rS = −0.313), daytime-SBP (rS = −0.267), nighttime-SBP (rS = −0,245) and nighttime DBP (rS = −0.344). On the opposite, total amount of saturated FA (SFA) and specifically, palmitic acid, correlated positively with waist circumference (rS = 0.254), waist/hip ratio (rS = 0.247), total cholesterol (rS = 0.258), triglycerides (rS = 0.373) and fasting insulin (rS = 0.287). Thirty-five children (50%) had hepatic steatosis detected by ultrasounds. Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was directly correlated to SFA (rS = 0.479), palmitic acid (rS = 0.515) and inversely to omega-6 FA (rS = −0.435) and AA (rS = −0.472). AA was inversely correlated with ALT (rS = −0.331) and palmitic acid directly with GGT (rS = 0.339). Conclusions: Omega-6 FA, and especially AA, may be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.

Low 25-hydroxyvitamin D level is not an independent risk factor for hepatosteatosis in obese children.

Obesity is an important risk factor for non-alcoholic fatty liver disease. Few studies have evaluated the association between vitamin D and non-alcoholic fatty liver disease in obese children. Therefore, we conducted a study to examine the relationship of vitamin D levels and hepatosteatosis in obese children. One hundred and eleven children with obesity participated in this study. Hepatosteatosis was diagnosed and graded using ultrasonography in all patients. Study participants were divided based on the presence of hepatosteatosis into two subgroups (hepatosteatosis and non-hepatosteatosis). Serum levels of 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, parathormone, and lipids were measured and compared. Hepatosteatosis existed in 52% of obese children without chronic diseases. There was no statistically significant difference in the vitamin D level between the hepatosteatosis and non-hepatosteatosis groups. Alanine aminotransferase levels and the triglycerides-to-high density lipoprotein ratio were significantly higher, and the high density lipoprotein levels were significantly lower in the hepatosteatosis group compared to the non-hepatosteatosis group. Vitamin D deficiency is not directly related with hepatosteatosis. A high ALT level and a high triglycerides-to-HDL ratio and low HDL levels are more significant in hepatic steatosis in obese children.

Association between the corrected QT interval, carotid artery intima-media thickness, and hepatic steatosis in obese children.

Objective:Childhood obesity is related to subclinical atherosclerosis. Carotid intima-media thickness (CIMT) and hepatosteatosis are parameters that reflect subclinical atherosclerosis and are shown to be associated with obesity. However, their relation with the corrected QT interval (QTc) has not been thoroughly studied in children. Here, we aimed to research the relation between QTc, hepatic steatosis, and CIMT among obese children.Methods:Fifty-three obese and 53 age- and sex-matched non-obese children aged 6–16 years were included in this prospective cross-sectional study. The QTc of each subject was accordingly obtained from lead II on a 12-lead resting electrocardiogram. Thus, CIMT measurement and abdominal ultrasonographic examination were performed. The data for obese and non-obese children were analyzed and compared.Result:The age and gender distribution of the subjects were statistically similar. The CIMT value of the obese group was higher than that of the non-obese group (p<0.001). The obese group had a higher frequency of hepatosteatosis at grade 1 or 2 than the non-obese group (p<0.001). The QTc values were also found to be more prolonged in the obese group than in the other group (p<0.001). With Student’s t-test and Mann-Whitey U test accordingly.Conclusion:We demonstrated that obese children had higher CIMT and QTc values as well as more frequent hepatosteatosis, and that the presence of hepatosteatosis or increased CIMT had an association with prolonged QTc values in obese children. Therefore, with the aim of detecting cardiovascular effects of obesity, it may be beneficial to perform the measurements of QTc in the presence of hepatosteatosis and/or increased CIMT among obese children.

Hepatic steatosis in obese children and adolescents

To assess the frequency of hepatic steatosis and metabolic syndrome among obese children and adolescents. A descriptive case series was conducted with 77 patients, aged 2 to 13 years and 11 months, who were followed up from February to July 2007. Obesity was defined as body mass index ≥ P95 adjusted for age and sex. Liver ultrasound was performed to diagnose hepatic steatosis. Metabolic syndrome was defined according to the modified criteria suggested by Cook et al. Hepatic steatosis was diagnosed in 33/77 patients (42.9%), 25/33 (75.8%) with mild steatosis and 8/33 (24.2%) with moderate steatosis. Those aged less than 10 years showed only mild steatosis, and the moderate degree of the disease was restricted to adolescents. Aminotransferase alterations were found in 9.1% (3/33) of patients with hepatic steatosis and in 4.9% (2/41) of those without the disorder. Mean waist circumference was 84.74±2.84 cm for patients with hepatic steatosis and 78.24±1.60 cm for those without the disease (p = 0.04). Metabolic syndrome was diagnosed in 27.3% (21/77) of obese patients, 47.6% (10/21) of them having steatosis, 60% had mild steatosis and 40% had a moderate degree of the disorder. The frequency of hepatic steatosis and metabolic syndrome was high. The association of larger waist circumference with hepatic steatosis highlights the importance of taking this parameter into consideration when investigating obese patients.

PP29 ANTILACTOFERRIN ANTIBODIES IN PEDIATRIC PATIENTS: PRIMARY SCLEROSING CHOLANGITIS OR ULCERATIVE COLITIS?

PP30 – Table 1 Glucose Insulin HOMA Cholesterol Triglyceride TNF-α 6-keto PG (mg/dl) (μUI/ml) (mg/dl) (mg/dl) (pg/ml) (pg/ml) Group A (76 pts) 89.3±6.6 14.6±7.7 3.2±1.7 161±29 105.4±60 10.1±5.4 185.1±24.1 (44 pts) Group B (80 pts) 88.0±8.5 11.0±5.8 2.4±1.3 162±32 85.4±50 14±7.5 492.6±91.8 (26 pts) p NS 0.001 0.002 NS 0.025 NS 0.002 and cirrhosis) usually occur in middle and late age, atherosclerotic process in the vascular wall and liver damage might begin very early in obese children. Aim of the study: was to investigate, in children attending our outpatient clinic for obesity, 1) any early vascular structural change and the presence of fatty liver; 2) any possible metabolic risk factor. Patients and methods: the study population consisted of 156 children (71 girls), whose BMI z-score was 4.5±1.4 and their mean age was 8.2±2.7 years. They all underwent ultrasonography to measure the intima-media thickness (IMT) of carotids and to study the morphology of the liver. Their serum glucose, insulin, HOMA index, lipids, TNF-α were measured as well. For those who gave their consent (70 pts), 6-keto PGF 1α was also evaluated. Results: according to IMT measurement, patients were divided in Group A (0.6-0.7 mm) with a BMI z-score of 4.6±1.4* and Group B (0.4-0.5 mm) with a BMI z-score of 4.1±0.9* (*p= 0.2). Their data are reported in Table 1. Liver steatosis was present in 23/76 pts of Group A (30.2%) and in 11/80 pts of Group B (13.7%) Conclusions: Increased carotid IMT was documented in 76/156 children (48.7%) and fatty liver in 34/156 (21.8%). Fasting insulin levels, HOMA index, triglyceride levels and 6-Keto-PGF1α were significantly different between Group A and Group B. These data might suggest that higher insulin resistance and triglyceride levels, together with low levels of 6-keto PGF 1α could be considered risk factors for early vascular damage and hepatic steatosis in obese children.

PP30 LOW LEVELS OF 6-KETO PGF 1α AND INCREASED CAROTID INTIMA–MEDIA THICKNESS IN OBESE CHILDREN WITH INSULIN RESISTANCE

PP30 – Table 1 Glucose Insulin HOMA Cholesterol Triglyceride TNF-α 6-keto PG (mg/dl) (μUI/ml) (mg/dl) (mg/dl) (pg/ml) (pg/ml) Group A (76 pts) 89.3±6.6 14.6±7.7 3.2±1.7 161±29 105.4±60 10.1±5.4 185.1±24.1 (44 pts) Group B (80 pts) 88.0±8.5 11.0±5.8 2.4±1.3 162±32 85.4±50 14±7.5 492.6±91.8 (26 pts) p NS 0.001 0.002 NS 0.025 NS 0.002 and cirrhosis) usually occur in middle and late age, atherosclerotic process in the vascular wall and liver damage might begin very early in obese children. Aim of the study: was to investigate, in children attending our outpatient clinic for obesity, 1) any early vascular structural change and the presence of fatty liver; 2) any possible metabolic risk factor. Patients and methods: the study population consisted of 156 children (71 girls), whose BMI z-score was 4.5±1.4 and their mean age was 8.2±2.7 years. They all underwent ultrasonography to measure the intima-media thickness (IMT) of carotids and to study the morphology of the liver. Their serum glucose, insulin, HOMA index, lipids, TNF-α were measured as well. For those who gave their consent (70 pts), 6-keto PGF 1α was also evaluated. Results: according to IMT measurement, patients were divided in Group A (0.6-0.7 mm) with a BMI z-score of 4.6±1.4* and Group B (0.4-0.5 mm) with a BMI z-score of 4.1±0.9* (*p= 0.2). Their data are reported in Table 1. Liver steatosis was present in 23/76 pts of Group A (30.2%) and in 11/80 pts of Group B (13.7%) Conclusions: Increased carotid IMT was documented in 76/156 children (48.7%) and fatty liver in 34/156 (21.8%). Fasting insulin levels, HOMA index, triglyceride levels and 6-Keto-PGF1α were significantly different between Group A and Group B. These data might suggest that higher insulin resistance and triglyceride levels, together with low levels of 6-keto PGF 1α could be considered risk factors for early vascular damage and hepatic steatosis in obese children.

MRI in Identifying Hepatic Steatosis in Obese Children and Relation to Ultrasonography and Metabolic Findings

The aim of this study was to identify nonalcoholic fatty liver in obese children by magnetic resonance imaging (MRI) and to compare the findings with the data from ultrasonography and from clinical and laboratory testing. Sixty obese children, 6 to 14 years old, underwent hepatic MRI and abdominal ultrasonography. Biochemistry determinations included serum aminotransferases, lipid profile, glucose, and insulin. Anthropometry included body mass index, total and trunk fat, and fat-free mass obtained by dual-energy radiographic absorptiometry. Hepatic steatosis, judged as hepatic fat fraction by MRI, was >or=9%. By MRI, 14 (23%) children had hepatic steatosis; of those, 5 had a fat fraction of 9% to 18%, and 9 had a fat fraction >18%. At univariate analysis, fat fraction was positively associated with being male, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase, body mass index z score, insulin, systolic pressure, and total and trunk fat mass. Hepatic steatosis was independently associated with alanine aminotransferase (P < 0.01). Overall, liver echogenicity on ultrasonography correlated well with fat fraction by MRI (correlation coefficient 0.527, P < 0.0001). Among the 27 children with increased liver echogenicity, 13 (48%) had hepatic fat fraction >or=9%, and 89% of children with echogenicity graded 2 or 3 had fat fraction >18%. All of the children (n = 9) with fat fraction >18% had increased liver echogenicity, and in 8 of them it was graded 2 or 3, but the MRI fat fraction ranged greatly (28%-45%). In obese children, nonalcoholic hepatic steatosis may be associated with the metabolic syndrome. Ultrasonography may be valuable in identifying high hepatic fat accumulation, but its ability to identify lower fat accumulation in the liver is scanty compared with MRI.