Thyroid Function in Obese Children with Non-Alcoholic Fatty Liver Disease

Ob­jec­ti­ve: To investigate the relationships between thyroid function and metabolic risk factors in obese adolescents with non-alcoholic fatty liver disease (NAFLD).Methods: One hundred sixty obese adolescents and 40 control subjects were enrolled in the study. The obese subjects were divided into two groups based on presence or absence of liver steatosis (NAFLD group and non-NAFLD group). Serum samples were assayed for glucose, insulin, cholesterol, alanine aminotransferase, aspartate aminotransferase, free thyroxine (fT4), free triiodothyronine (fT3) and thyroid-stimulating hormone (TSH). The ratio of fT3 to fT4 was evaluated as an indirect index of deiodinase activity. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples.Results: NAFLD and non-NAFLD groups had slightly higher fasting blood glucose values than the control group. Fasting insulin levels in the NAFLD group were significantly higher than those in the non-NAFLD and control groups. The NAFLD group had significantly greater HOMA-IR values compared with the non-NAFLD group and also with the control group. The NAFLD group had significantly higher fT3/fT4 ratio values compared to both non-NAFLD and control groups. fT3/fT4 was positively correlated with serum insulin levels in the NAFLD group. Conclusion: This study showed that obese adolescents with hepatosteatosis had elevated values for fT3/fT4 ratio. This finding suggested a high conversion of T4 to T3 due to increased deiodinase activity as a compensatory mechanism for fat accumulation.     

Impact of Pemafibrate in Patients with Hypertriglyceridemia and Metabolic Dysfunction-associated Fatty Liver Disease Pathologically Diagnosed with Non-alcoholic Steatohepatitis: A Retrospective,Single-arm Study

Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline [AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively], especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.     

Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease

Background: Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD.Methods: We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced.Results: In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosisConclusion: Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.     

Non-alcoholic fatty liver disease: further expression of the metabolic syndrome

Non-alcoholic fatty liver disease has been associated with metabolic disorders, including central obesity, dyslipidemia, hypertension and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease refers to a wide spectrum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis, advanced fibrosis and cirrhosis.     

Predictors of Non-alcoholic Fatty Liver Disease in Obese and Overweight Egyptian Children: Single Center Study

Background/Aim:

Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children.

Materials and Methods:

Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients.

Results:

Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses.

Conclusion:

Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.     

Association Between Neutrophil-to-Lymphocyte Ratio with Inflammatory Activity and Fibrosis in Non-alcoholic Fatty Liver Disease

BackgroundInflammation plays an important role in the development and progression of non-alcoholic steatohepatitis (NASH), and NASH is a powerful driving force for the progression of fibrosis. The neutrophil-to-lymphocyte ratio (NLR) is a simple emerging indicator of inflammation. We aimed to assess the potential association between NLR and histological severity of non-alcoholic fatty liver disease (NAFLD).MethodsThis retrospective study consisted of 231 patients with biopsy-proven NAFLD in China from August 2017 to September 2019. The steatosis, activity, and fibrosis scoring system were used to evaluate liver biopsy tissue.ResultsOf the 231 patients with NAFLD, advanced inflammatory activity was present in 43.3% and significant fibrosis in 25.5% of patients. Multivariate logistic regression analysis showed NLR to be correlated with advanced inflammatory activity (Odds ratio (OR): 0.62, 95% CI: 0.42-0.94, P = .025) and significant fibrosis (OR: 0.57, 95% CI: 0.35-0.94, P = .028). The NLR was inversely associated with the degree of steatosis, lobular inflammation and fibrosis (r = −0.16, P = .014; r = −0.15, P = .019; r = −0.13, P = .046, respectively), but had no association with the severity of ballooning. The multivariate-adjusted models had good predictability for advanced inflammatory activity (area under curves (AUC) 0.790, 95% CI: 0.730-0.850) and for significant fibrosis (AUC 0.798, 95% CI: 0.728-0.868).ConclusionThis study showed negative correlations between elevated NLR levels with advanced inflammatory activity and significant fibrosis in patients with NAFLD. Our results also suggested that NLR could be considered as a simple and noninvasive mark to identify high-risk populations in NAFLD.     

胰岛素抵抗与代谢综合征

胰岛素对糖脂代谢、血压调控、血管收缩反应都有影响,胰岛素抵抗和/或代偿性高胰岛素血症可导致糖耐量异常、血脂异常、高血压、血管功能失调。随着胰岛素抵抗的出现,一些心血管危险因子往往聚集在一起形成代谢综合征,由于此综合征具有预测心血管疾病的内在价值,因此最近提出将代谢综合征提升为“疾病”。这些心血管危险因子的病理生理改变与胰岛素抵抗和代偿性高胰岛素血症密切相关,现对此进行综述。     

Effects of ACE Inhibitors on Insulin Resistance and Lipid Profile in Children with Metabolic Syndrome

Objective: The aim of this study was to evaluate the effects of using ACE inhibitors on insulin resistance, glucose metabolism, body fat composition, and lipid profile in children over 10 years of age with obesity-associated metabolic syndrome (MS).Methods: A total of 53 children with MS, who had been followed for at least one year were included in the study. The sample was divided into two groups: Group 1-30 obese children (13 female, 17 male) who were not using an ACE inhibitor and Group 2-23 obese children (13 female, 10 male) who were using an ACE inhibitor. Anthropometric and laboratory dataobtained at baseline and at the 3rd, 6th, and 12th months of follow-up were compared in the two groups.Results: Comparison of the data in the two groups at 3rd, 6th, and 12th months revealed no statistically significant differences in terms of weight standard deviation score (SDS), body mass index SDS, weight for height percentile, body fat percentage, and very low-density lipoprotein (VLDL)values. However, there were statistically significant differences in mean glucose and insulin levels, homeostasis model assessment for insulin resistance, LDL and high-density lipoprotein values, and highly significant differences in mean triglyceride values.Conclusions: The positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. Randomized, controlled, double-blind, and long-term studies are needed for a definitive conclusion. Conflict of interest:None declared.     

高血压合并非酒精性脂肪肝的临床特点

目的探讨代谢综合征(MS)、原发性高血压(EH)与非酒精性脂肪肝(NAFL)之间的关系。方法选择2006-01-2007-09在我院接受肝脏 B 超检查的409例高血压住院患者(MS 312例,无 MS 97例),根据超声影像的结果分为脂肪肝组(246例)与非脂肪肝组(163例),测定血脂、肝功、肾功、血糖。结果 1)MS+EH 组NAFL 的检出率(66.0%)明显高于 EH 非 MS 组(66.0%比41.2%,P<0.01);2)EH 合并 NAFL 组(EH+NAFL 组)的体质量指数、总胆固醇(TC)、三酰甘油(TG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ谷氨酰转肽酶(GGT)、空腹血糖、口服葡萄糖耐量试验(OGTT)2 h 血糖(2 h PG)均较 EH 不合并NAFL 组即单纯高血压组(EH组)(n=151)增高;体质量指数[EH+NAFL 组:(27.8±4.0)比 EH 组:(25.4±3.2)kg/m~2,P<0.01];TC[EH+NAFL 组:(4.6±1.1)比 EH 组:(4.3±0.9)mmol/L,P<0.05],TG[EH+NAFL 组:(2.4±1....     

Higher Metabolic Syndrome in Obese Asthmatic Compared to Obese Nonasthmatic Adolescent Males

The relationship between asthma and obesity has been documented in children and adolescents; however, few studies on metabolic syndrome and asthma have been performed. Objective. To determine the prevalence of metabolic syndrome in adolescents among the following groups: obese with asthma (OA), obese without asthma (ONA), nonobese with asthma (NOA), and nonobese without asthma (NONA). Patients and Methods. The authors measured anthropometric (height, weight, waist circumference, body mass index, and waist-hip ratio), clinical (Tanner stage, blood pressure, fat and muscle reserve, and exercise), and biochemical parameters (basal and load glucose, cholesterol, triglycerides, high-density lipoproteins, uric acid, and insulin) in 500 Mexican adolescents. Results. A total of 111 OA, 198 ONA, 63 NOA, and 71 NONA adolescents completed the study. There were no differences in age, height, Tanner stage, high-density lipoproteins, or basal glucose among groups. Cholesterol, triglycerides, uric acid, basal insulin, and homeostasis model assessment (HOMA)-IR were significantly higher among the obese than nonobese groups but were similar between the OA and ONA groups. The prevalence of impaired fasting glucose was significantly higher among ONA versus OA males. The prevalence of metabolic syndrome (define as ≥3 abnormal cardiometabolic risk factors by de Ferranti, Cook, and International Diabetes Federation [IDF] criteria) was higher among OA teens than in the ONA group; however, this association was significant only among males. Adolescents from the ONA group were able to perform significantly more vigorous exercise than the other groups. Conclusion. Adolescent males who were obese and also had mild persistent asthma had a significantly higher prevalence of metabolic syndrome than obese males without asthma. However, overall, asthma seems to confer a protective effect against the prediabetes condition in males.     

非酒精性脂肪性肝病与代谢综合征相关性的临床研究

目的分析非酒精性脂肪性肝病与代谢综合征的关系。方法按住院顺序选择有随访资料病例共185例,将其分为四组（单纯脂肪肝组、单纯肥胖组、脂肪肝＋肥胖组、正常对照组）,在基线水平对四组出现代谢综合征情况进行横向比较。其次,在随访后再次对四组出现代谢综合征情况进行组内、组间比较。结果随访结束时,单纯脂肪肝组代谢综合征发病率明显高于正常对照组（P〈0.05）。结论非酒精性脂肪性肝病促进代谢综合征的发生,且不依赖于肥胖。     

Assessment of Cardiovascular Parameters in Obese Children and Adolescents with Non-Alcoholic Fatty Liver Disease

Objective:The aim of this study was to evaluate the periaortic fat thickness (PAFT) using conventional echocardiography in obese children and adolescents with non-alcoholic fatty liver disease (NAFLD).Methods:Two hundred and ninety-seven obese children and adolescents were included in the study. Anthropometric measurements were made in all subjects, and fasting venous blood samples were taken for determination of glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Ultrasonography of the liver was used for assessment of NAFLD and the subjects were grouped as NAFLD and non-NAFLD. Echocardiography was performed in all subjects.Results:PAFT was higher in patients with NAFLD compared with the non-NAFLD group. In patients with NAFLD, PAFT was positively correlated with waist circumference and with total cholesterol levels. In multiple regression analysis, waist circumference (β=0.28, p=<0.001) was found to be the best predictor of PAFT.Conclusion:Conventional echocardiography may be used to determine increased PAFT at an early stage in obese children and adolescents with NAFLD for careful monitoring of cardiovascular risk.     

非酒精性脂肪肝患者血清抵抗素与胰岛素抵抗关系的研究

目的 探讨非酒精性脂肪肝患者血清抵抗素水平及其与肥胖、胰岛素抵抗、血糖、血脂的关系.方法 选择非酒精性脂肪肝患者100例,正常对照30例,采用ELISA方法测定空腹血清抵抗素,同时检测其身高、体重、腰围、臀嗣、血糖、血脂、肝功能及胰岛素水平,并计算体重指数、腰臀比和胰岛索敏感指数.结果 非酒精性脂肪肝患者血清抵抗素水平为17.68±5.2 ng.ml,高于正常对照组的12.85±4.4 ng.ml,P<0.01.相关分析显示,血清抵抗素与体重指数、甘油三酯呈正相关关系(分别为r=0.376、0.426,P<0.05),与胰岛素敏感指数呈负相关关系,(r=-0.584,P<0.01),而与腰臀比、总胆固醇、低密度酯蛋白胆固醇、高密度脂蛋白胆固醇、血糖无相关性,(P>0.05).结论 在非酒精性脂肪肝的发病过程中,抵抗素可能参与了胰岛素抵抗.     

Nonalcoholic Fatty Liver Disease: A Clinical Review

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.     

Influence of Insulin Resistance and Adipokines in the Grade of Steatosis of Nonalcoholic Fatty Liver Disease

The objective of this work was to study the influence of insulin resistance and adipokines on the grade of steatosis in patients with NAFLD (nonalcoholic fatty liver disease) diagnosed by liver biopsy. A sample of 24 NAFLD patients was analyzed in a cross-sectional study. All patients with a two-week weight-stabilization period before recruitment were enrolled. A liver biopsy was realized. Weight, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and adipokines blood levels were measured. A nutritional evaluation (dietary intake, indirect calorimetry, and bioimpedance) was performed. The mean age was 41.6 ± 8.7 years and the mean body mass index (BMI) 29.4 ± 4.7. Twelve patients had a low grade of steatosis (grade 1 of the Brunt classification) and 12 patients had a high grade of steatosis (grade 2 or 3). Only HOMA was higher in patients with a high grade of steatosis (1.4 ± 0.5 vs. 2.8 ± 1.7 units; P < 0.05). Anthropometric data and dietary intake were similar for both groups. Blood levels of adiponectin were higher in patients with a low grade of steatosis (37.7 ± 22.5 vs. 24.2 ± 33 ng mL⁻¹; P < 0.05). Blood levels of resistin were higher in patients with a high grade of steatosis (2.36 ± 0.6 vs. 2.8 ± 0.6 mg mL⁻¹; P < 0.05), without differences in TNF-α or leptin levels. In logistic regression analysis, the HOMA-IR remained in the model, with an odds ratio to develop high grade of steatosis of 7.8 (95% CI: 1.8–75) with each 1 unit of HOMA-IR adjusted by age, sex, BMI, and dietary intake. This study demonstrates that insulin resistance determined with the HOMA model is associated with a high grade of steatosis in patients with NAFLD.     

Safety and Effectiveness of Essential Phospholipids Paste in Patients with Non-alcoholic Fatty Liver Disease or Viral Hepatitis

Background: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis.Methods: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL.Results: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period.Conclusion: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.     

Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course

Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered.