Nonalcoholic Steatohepatitis In Children Research Articles

Effects of probiotics and high fructose diet on De Ritis ratio, TGF-B levels, and liver histopathology of Sprague Dawley rats

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Histopathological diagnosis has been the gold standard for diagnosing and determining the severity of non-alcoholic steatohepatitis (NASH). However, this method is invasive, especially for diagnosing NASH in children. This research aimed to study the effect of probiotics on the De Ritis ratio, TGF-β levels, and histopathological changes in rats given High Fat, High Fructose (HFHFr) diet to look at the correlation between the De Ritis ratio and liver histopathology in diagnosing NAFLD. Method: Twenty-one male Sprague Dawley rats were included and divided into three groups. In the first group, as control only received a normal chow diet for eight weeks. The second group received an HFHFr diet for eight weeks, and the last group received HFHFr for eight weeks and a combination of HFHFr and probiotics for another eight weeks. After decapitation, we took 3 ml of serum from each rat to measure AST, ALT, and TGF-β. A 4 μm thick liver tissue slide was taken and stained with Hematoxylin – Eosin Stain for histopathological analysis. We used the Non-Alcoholic Steatohepatitis (NAS) Score for measuring liver damage progression. Results: De Ritis ratio and TGF-β level did not significantly differ between probiotic and non-probiotic groups (p = 0.064 and 0.383), but there was a significant NAS score difference (p = 0.001) in probiotic and non-probiotic groups. This was followed by a significant correlation between the De Ritis ratio and the NAS score (r = 0.613, p = 0.003). Conclusion: Probiotic supplementation alleviated liver damage caused by the HFHFr diet but did not successfully reduce the De Ritis ratio or improve TGF-β.

Correlation between Transient Elastography (Fibroscan®) and Ultrasonographic and Computed Tomographic Grading in Pediatric Nonalcoholic Steatohepatitis.

PurposeThis study aimed to examine the advantages and usefulness of transient elastography (Fibroscan®) in diagnosing non-alcoholic steatohepatitis in children and adolescents compared to those of abdominal computed tomography and liver ultrasonography.MethodsForty-six children and adolescent participants aged between 6 and 16 years who underwent transient elastography (Fibroscan®) as well as liver ultrasonography or abdominal computed tomography were included. Thirty-nine participants underwent liver ultrasonography and 11 underwent computed tomography. The physical measurements, blood test results, presence of metabolic syndrome, and the degree of liver steatosis and liver fibrosis were analyzed, and their correlations with transient elastography (Fibroscan®), abdominal computed tomography, and liver ultrasonography, as well as the correlations between examinations, were analyzed.ResultsThirty-six participants (78.3%) were boys, and the mean age was 12.29±2.57 years, with a mean body mass index of 27.88±4.28. In the 46 participants, the mean values for aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 89.87±118.69 IU/L, 138.54±141.79 IU/L, and 0.77±0.61 mg/dL, respectively. Although transient elastography (Fibroscan®) and abdominal computed tomography grading had a statistically significant positive correlation with aspartate aminotransferase and alanine aminotransferase values, the correlations between the results of grading performed by transient elastography (Fibroscan®), abdominal computed tomography, and liver ultrasonography were not statistically.ConclusionWe confirmed that each examination was correlated with the results of some blood tests, suggesting the usefulness and possibility of diagnosis and treatment of steatohepatitis mediated by transient elastography (Fibroscan®) in the department of pediatrics.

Polyunsaturated fatty acids: omega-3 and omega-6 and nonalcoholic fatty liver disease

The history of the study of polyunsaturated fatty acids (PUFAs) began over 100 years ago. In 1909. P. Hartley isolated arachidonic acid. Later, 21 years later, Burr and Burr in 1930 showed its positive effect on the growth and development of rats. The important thing about this work was that after reintroduction of PUFAs into the diet of rodents, body functions began to recover. It took over 60 years from the time of the discovery of arachidonic acid to prove its effect on the cardiovascular system. Today, research into the effects of long-chain PUFAs on human health, intelligence, the immune system, neuronal connections, the course of pregnancy and infant health has led to recommendations for the widespread use of foods or supplements containing omega-3 PUFAs. Unbalanced diets in children and adolescents, selective appetite, and eating disorders lead to the development of deficit conditions, cognitive impairment, obesity, and metabolic syndrome with liver damage. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are asymptomatic in the early stages, but it is during this period that the prognosis in children can be changed. This article reviews international recommendations for the integrated use of long-chain PUFAs in the treatment of NAFLD and NASH in children. Supplementation of the diet with high-quality purified fish oil replenishes the requirement, improves disease prognosis, reduces insulin resistance and the level of liver fibrosis in patients with NAFLD and NASH.

A study of occurrence of non-alcoholic steatohepatitis in children with obesity and overweight

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and its increasingprevalence is associated with a concomitant rise in obesity. Anthropometric measurements and non-invasive tests (liver function tests and USG abdomen) help in early recognition of non-alcoholic steatohepatitis (NASH) and reduce consequent morbidity and mortality. Aim: This study aims to study the occurrence of NASH in obese and overweight children and to derive the correlation of NASH with clinical and biochemical parameters in overweight and obese children. Methods: This hospital-based prospective study included children (age?18 years) who met the inclusion criteria. Diagnosis of NASH was based on the USG abdomen. Measurements included anthropometry, ultrasonography, fasting glucose, alanine aminotransferase (ALT), lipid profile and additional parameters of blood pressure, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). The variables were compared between children with and without NASH. Results: A total of 146 patients (female: 51.4%, male: 48.6%) were enrolled in the study. The most common age group affected was 11–18 years (50.7%) followed by 6–10 years (43.2%) and <5 years (6.2%). The occurrence of NASH in the study group was 63% of obese and overweight children. Mean weight, body mass index (BMI), waist circumference, waist-hip ratio, blood pressure (BP), serum glutamic-pyruvic transaminase (SGPT), fasting insulin level, and HOMA-IR were significantly higher in children with NASH. There was a significant association between SGPT and NASH. Elevated SGPT of 79.3% and 1.9% were observed among the subjects with and without NASH, respectively. Conclusion: Anthropometric indices and biochemical parameters were more elevated in the NASH group showing its direct correlation with hepatic steatosis.

Diagnostic accuracy of apoptosis markers in non-alcoholic fatty liver disease in children

Introduction. Non-alcoholic fatty liver disease (NAFLD) is recognized as one of the most common chronic liver diseases in children and adults worldwide. Early diagnosis of rapidly progressive forms of NAFLD – non-alcoholic steatohepatitis (NASH) – is crucial, because therapeutic intervention in the early disease stages creates unique opportunities for the reversal of pathological changes and restoration of liver structure and function. Despite the variety of currently available diagnostic scales and indices, laboratory diagnosis of NAFLD in children requires new non-invasive tests and their validation.Aim: To investigate the differences of cytokeratin-18 (CK18) and the combined marker MACK-3 levels in children with nonalcoholic steatohepatitis (NASH), simple hepatic steatosis, overweight and obese children without hepatic steatosis.Materials and methods. The study included 170 patients aged 6 to 17 years. The mean age of patients was (12.15 ± 2.51) years. According to the presence of steatosis, steatohepatitis, overweight and obesity, patients were divided into 4 groups: the 1st group consisted of 37 patients with NASH, the 2nd group – 53 patients with simple steatosis, the 3rd group – 65 overweight and obese patients without hepatic steatosis, the 4th group (control) – 15 patients with normal weight without steatosis. Biochemical hepatogram, carbohydrate metabolism investigation, as well as CK18 enzyme-linked immunosorbent assay, were conducted with the MACK-3 calculation.Results. The average level of CK18 in children with NASH increased by 1.6 times (P <0.05) compared with children of the control group. The median CK18 level in patients with NASH was by 1.6 times (P < 0.05) and 2.0 times (P < 0.05) higher than in groups 2 and 3, respectively. T he threshold level of CK18 for the diagnosis of NASH was 87.4 U/l: its sensitivity was 81.8 %, specificity 70 %, AUROC 0.736 (P ˂ 0.05). Calculated index MACK-3 revealed a significant increase in children with NASH compared with other groups (P < 0,05). Threshold level of MACK-3 for the diagnosis of NASH was 0.053: sensitivity – 90.9 %, specificity – 81.6 %, AUROC 0.958 (P ˂ 0.05).Conclusions. Thus, in children with NASH, a significant increase in the CK18 level was found, which can be used for early non-invasive diagnosis of NASH in children. The advantage of the calculated index MACK-3 is the increase in diagnostic accuracy and the possibility of its use to stratify the risk of the progressive course of NAFLD, which will streamline the selection of patients for active therapeutic intervention.

Increased atherogenic lipoprotein profile in children with non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) has been shown to be an independent risk factor for cardiovascular disease. In adults, histologic severity of non-alcoholic steatohepatitis (NASH) is associated with a more atherogenic profile. To assess cardiovascular disease risk by lipoprotein profile in children with NAFLD and compare to histologic assessment of severity. Nuclear magnetic resonance lipoprotein profile including lipoprotein particle sizes, apolipoproteins and the lipoprotein insulin resistance (LP-IR) index was measured in serum samples collected from 76 children at the time of a clinically indicated liver biopsy for NAFLD. Liver histology was scored using the NASH Clinical Research Network criteria and grouped into NASH or non-NASH. Children with NASH had higher apolipoprotein B to apolipoprotein AI, ApoB/ApoAI (0.56 [IQR, 0.45-0.70] vs 0.66 [IQR, 0.56-0.79], P = .02) and higher LP-IR index (61 ± 21.9 vs 68 ± 17.3, P = .05) compared to children with non-NASH. Severity of hepatocyte ballooning was associated with higher ApoB/ApoAI ratios (P = .01), while high-density lipoprotein size was inversely associated with hepatic fat accumulation (P = .04). While dyslipidaemia is common among children with NAFLD, this data suggests severity of the histologic features is closely associated with severity of cardiometabolic risk. Further studies are needed to understand the role of treatment of NASH in children to prevent future cardiometabolic disease.

P018 The Nox2: the new marker of stress oxidative in non-alcoholic steatohepatitis in children

P018 The Nox2: the new marker of stress oxidative in non-alcoholic steatohepatitis in children

Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents

Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alcoholic steatohepatitis (NASH). Our aim was to investigate the factors associated with NASH in children and adolescents with proven NAFLD, and to test whether UA concentrations and fructose consumption are independently associated with NASH. Obese children with NAFLD were studied (n=271). NASH was diagnosed by a NAFLD activity score ⩾5 and the fatty liver inhibition of progression (FLIP) algorithm. Fructose consumption (g/day) was assessed by food frequency questionnaire, and UA (mg/dl) was measured in serum. Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with NASH. NASH occurred in 37.6% of patients. Hyperuricaemia (UA ⩾5.9mg/dl) was present in 47% of patients with NASH compared with 29.7% of non-NASH patients (p=0.003). Both UA concentration (OR=2.488, 95% CI: 1.87-2.83, p=0.004) and fructose consumption (OR=1.612, 95% CI 1.25-1.86, p=0.001) were independently associated with NASH, after adjustment for multiple (and all) measured confounders. Fructose consumption was independently associated with hyperuricaemia (OR=2.021, 95% CI: 1.66-2.78, p=0.01). These data were confirmed using the FLIP algorithm. Both dietary fructose consumption and serum UA concentrations are independently associated with NASH. Fructose consumption was the only factor independently associated with serum UA concentration. Currently, it is not known whether dietary fructose consumption and uric acid (UA) concentration are linked with non-alcoholic steatohepatitis (NASH) in children and adolescents. Our aim was to test whether UA concentrations and fructose consumption are independently associated with NASH in children and adolescents with proven non-alcoholic fatty liver disease (NAFLD). We show that both dietary fructose consumption and serum UA concentrations are independently associated with NASH and fructose consumption was independently linked with high serum UA concentrations.

Nonalcoholic Steatohepatitis (NASH) Has Surpassed Hepatitis C as the Leading Etiology for Listing for Liver Transplant: Implications for NASH in Children and Young Adults

Introduction: Nonalcoholic fatty liver disease (NAFLD) affects up to 10% of the pediatric population and 30% of adults in North America. The natural course of the disease in children and young adults is not well characterized and the public health impact of the disease in these populations is not clear. We hypothesized that if NAFLD is progressive in children and young adults, one would expect to see an increase in the number of adults under the age of fifty years who develop NAFLD-related end stage liver disease requiring listing for liver transplantation. The aim of this study was to evaluate the trends in subjects with NAFLD listed for liver transplant in adults under the age of 50 years and relate them to trends for other etiologies. Methods: Data were obtained from the United Network for Organ Sharing (UNOS) registry from 2002 to 2015. Adults (18 years and above) on the liver transplant waitlist were grouped as follows: 18-34 years; 35-49 years; 50-64 years; and 65+ years. We determined the primary etiology, by year, of end stage liver disease in waitlist registrants, including nonalcoholic steatohepatitis (NASH), cryptogenic cirrhosis (CC) and hepatitis C virus (HCV). Subjects with the etiologies of NASH and CC were combined. The number of waitlist registrants within each category was plotted as a function of time and differences between slopes were compared.Figure 1Results: The total number of adults under 50 years being listed for liver transplant regardless of etiology declined from 1776 to 704 from 2002-2014. Amongst those between 18-34 years, the number of subjects being listed for transplant for NASH/CC remained flat whereas there was a remarkable increase in the number of subjects in the 35-49 year range. From 2002-2014, NASH/CC as an etiology amongst those listed for transplant increased by 124% whereas HCV declined by 78% (p < 0.0001). For 2015, with data available until August, NASH/CC (n=194) surpassed HCV (n=148) as the leading etiology for transplant listing in the 35-49 year group. A similar increase was present in those over the age of 50 years. Conclusion: NAFLD is now the leading indication for listing for liver transplantation in adults under 50 years. While overall rates for listing for transplant in this population has declined, the rates of listing for NAFLD-associated cirrhosis has doubled. Given the 20-30 year time frame for development of cirrhosis due to NAFLD, this suggests that NAFLD in pediatric age groups and young adults is a significant public health problem.

Диагностика и лечение неалкогольной жировой болезни печени и неалкогольного стеатогепатита у детей

Диагностика и лечение неалкогольной жировой болезни печени и неалкогольного стеатогепатита у детей

A non-invasive prediction model for non-alcoholic steatohepatitis in paediatric patients with non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease encompasses a spectrum of diseases that range from simple steatosis to the aggressive form of non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis is currently diagnosed through liver biopsy. AimTo develop a non-invasive predictive model of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. MethodsAnthropometric, laboratory, and histologic data were obtained in a cohort of children with biopsy-proven non-alcoholic fatty liver disease. Multivariable logistic regression analysis was employed to create a nomogram predicting the risk of non-alcoholic steatohepatitis. Internal validation was performed by bootstrapping. ResultsThree hundred and two children were included in this analysis with a mean age of 12.3±3.1 years, a mean body mass index percentile of 94.3±6.9, and non-alcoholic steatohepatitis was present in 67%. Following stepwise variable selection, total cholesterol, waist circumference percentile, and total bilirubin were included as variables in the model, with good discrimination with an area under the receiver operating characteristic curve of 0.737. ConclusionsA nomogram was constructed with reasonable accuracy that can predict the risk of non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease. If validated externally, this tool could be utilized as a non-invasive method to diagnose non-alcoholic steatohepatitis in children with non-alcoholic fatty liver disease.

Serum Cytokeratin-18 Fragment Levels Are Useful Biomarkers for Nonalcoholic Steatohepatitis in Children

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD). Noninvasive methods to identify children with NASH are urgently needed. The aim of this study was to evaluate the use of plasma cytokeratin-18 (CK18) fragment levels, a marker of increased hepatocyte apoptosis, as a non-invasive biomarker for pediatric NASH. Consecutive children with biopsy-proven NAFLD were included and blood samples were collected at the time of the biopsy. The diagnosis of NASH was based on Brunt's criteria. Histological features were scored: steatosis (0-3), lobular inflammation (0-3), ballooning (0-2), and portal inflammation (0-2). NAFLD activity score was calculated (0-8) and fibrosis stage was scored (0-4). We measured plasma CK18 levels using the M30-Apoptosense enzyme-linked immunosorbent assay kit. A total of 201 subjects were included in the study. The mean age was 10.7±2.5 years and 37% were male. NASH was diagnosed in 140 patients with a mean NAFLD activity scoring of 4.4±1.3. CK18 levels were significantly higher in subjects with NASH compared with not NASH (322.1 U/l±104.8 vs. 164.2 U/l±62, respectively; P<0.001). The risk of having NASH on liver biopsy increased with increased CK18 levels (P<0.001). For every 10 U/l increase in CK18 levels, the likelihood of having NASH increased by 70% after adjusting for multiple confounders. The performance of CK18 level for the diagnosis of NASH was excellent with an area under the receiver operating characteristics curve of 0.933. CK18 is a promising non-invasive biomarker for NASH in children with fatty liver disease.

Vitamin E and nonalcoholic fatty liver disease

Oxidative stress plays a central role in the transition from simple steatosis to nonalcoholic steatohepatitis (NASH). An effective therapeutic strategy is to target reduction in oxidative stress in NASH patients. The aim of this review is to discuss the role of oxidative stress in NASH and biological activities of vitamin E and present available evidence on the therapeutic efficacy of vitamin E in NASH. In Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, vitamin E therapy demonstrated a significant improvement in steatosis, inflammation, ballooning, and resolution of steatohepatitis in adult patients with aggressive NASH, who do not have diabetes or cirrhosis. Although vitamin E showed a significant resolution of NASH in children, a sustained reduction of alanine aminotransferase was not attained in The Treatment of nonalcoholic fatty liver disease (NAFLD) in Children (TONIC) trial. The prevalence of NAFLD is likely to increase over time due to the epidemics of obesity and diabetes. Presently, there is no definitive treatment for NAFLD. Based on available evidence, vitamin E (RRR-α-tocopherol) is only recommended in NASH adults without diabetes or cirrhosis and with aggressive histology. Validation is needed in children before its use can be recommended. Longer follow-up of randomized controlled trials are needed to assess long-term vitamin E safety.

275 Non-Alcoholic Fatty Liver Disease and Steatohepatitis in Taiwanese Children: The Prevalence and Serum Retinol Binding Protein 4 Level

Subjective: The aims of this study were to investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in schoolchildren with various body mass index (BMI). Moreover, the correlation between serum RBP4 level and liver injury was investigated. Methods: 847 schoolchildren aged 4 to 12 years were evaluated by anthropometric measurements. The serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides and cholesterol levels were measured after an 8-hour overnight fast. NAFLD was diagnosed as fatty infiltrates of liver in sonogram and NASH was defined as NAFLD with an elevated ALT level. Results: The prevalence of overweight (85th % 95th %) in schoolchildren was 14.8% and 11.4%, respectively. The mean age and male-to-female ratio were significantly higher in children with obesity than those with normal weight (P=0.001). The obese children had a higher rate of abnormal AST and ALT (P< 0.001) and higher fasting triglyceride (P< 0.001) and glucose (P=0.04) levels than those with normal weight. Among 245 children with ultrasound examinations, fatty liver disease was identified in 2.5%, 20.6%, and 68.2% of children with normal weight, overweight, and obesity, respectively. Nine (40.9%) subjects were diagnosed as NASH in children with obesity. The serum RBP4 level was significantly higher in children with NAFLD and NASH than that in normal (P< 0.05). Conclusions: Childhood obesity is closely related to male gender, increase of age, fasting triglycerides, and glucose levels. Moreover, the serum RBP4 level was parallel to the liver injury in children.

Serum hyaluronic acid for the screening of progressive nonalcoholic steatohepatitis in children: a promising approach

Nonalcoholic fatty liver disease (NAFLD) represents now the leading cause of liver disease in children in Western countries. NAFLD encompasses a wide spectrum of liver pathology ranging from simple uncomplicated steatosis to steatohepatitis (NASH), with possible progression to cirrhosis and hepatocarcinoma. Presently only liver biopsy can discriminate patients with NASH, but it remains a costly and invasive procedure, and in children is still perceived to carry a higher risk of complications, and is less accepted than in adults. Thus, there is an urgent need of noninvasive markers of NASH. In the present issue, Nobili and coworkers demonstrate that the evaluation of serum hyaluronic acid (HA), a relatively cheap, immediate, and readily available approach, predicts liver fibrosis independently of biochemical indices of liver damage in 100 children with NAFLD referred to a tertiary care center, and may allow to identify by a double cut-off approach those without fibrosis and those with moderate-severe fibrosis with a high specificity, without recurring to not yet available complex tests for the prediction of fibrosis requiring the evaluation of predictive algorithms. These findings represent a significant step forward and should be replicated in independent series followed at tertiary centers and, thanks to the relatively low cost of the method, in populations at lower risk of liver damage.

Metabolic Syndrome in Children and Adolescents: Prevalence, Public Health Issue, and Time for Initiative

Screening for features of the metabolic syndrome is being recommended by many learned societies and scientists in the field. Guidelines and recommendations as to how and whom to screen still vary from country to country and are not solely based on evidence from large, longitudinal studies. Whether the term ‘‘metabolic syndrome’’ is of clinical relevance in children and adolescents and more meaningful than individual components such as hypertension, insulin resistance, and type 2 diabetes mellitus or dyslipidemia is still open for debate. In addition, comorbidities of obesity such as sleep-disordered breathing and sleep apnea even at a young age have been recognized more recently. Nevertheless, along with the increasing prevalence of obesity in childhood and adolescence, the existence of the metabolic syndrome in obese children and adolescents is being recognized. The prevalence of any feature of the metabolic syndrome is being reported to be up to 30%, irrespective of the definition that is applied. Signaling molecules, termed adipocytokines, secreted from the adipose tissue, are thought to play a major role in the pathophysiology of the metabolic syndrome. Leptin and its soluble receptor may be more important in states of energy deficiency rather than as a predictor of the metabolic syndrome in

A case of hepatopulmonary syndrome in a child with fatty liver disease secondary to hypopituitarism after craniopharyngioma resection

Hepatopulmonary syndrome is a triad that includes: hepatic dysfunction, intrapulmonary vascular dilatationand abnormal arterial oxygenation. The incidence of intrapulmonary vascular dilatations, in adults with end-stage liver disease, has been reported to be 13% to 47%, however the incidence in children is unclear and the cases in Korean children have never been reported. The hepatopulmonary syndrome may occur as a result of chronic liver disease following nonalcoholic steatohepatitis in children with hypothalamic or pituitary dysfunction. We report a case of hepatopulmonary syndrome in a 13-yearold child who had rapidly progressive liver dysfunction secondary to panhypopituitarism after craniopharyngioma resection. Careful monitoring and treatment of endocrine abnormalities and metabolic status, as well as liver function, are required in all children undergoing pituitary tumor resection.

Nonalcoholic steatohepatitis in children.

Nonalcoholic steatohepatitis (NASH) is one entity in a spectrum of chronic liver disease related to obesity, hyperinsulinemia, insulin resistance, and liver cell injury from free fatty acid toxicity or other oxidant stress. The more inclusive term "nonalcoholic fatty liver disease" (NAFLD) is increasingly being used to encompass the entire spectrum, which includes simple hepatic steatosis without inflammation (which may not lead to progressive liver injury), NASH itself, and the resulting cirrhosis (which may be devoid of steatosis). Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. Pediatric NASH is a serious complication of childhood obesity.

Steatohepatitis in obese individuals

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20–40% in obese patients. Since NASH is associated with obesity, prevalence has been predicted to increase along with the arsent epidemic of obesity and type II diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in 25% and 10% in these patients respectively over a 10-year period. This is of particular concern given the increasing recognition of NASH in children. Treatment consists of treating obesity and its co-morbidities; diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in body weight. Bariatric surgery is indicated in selected patients. A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.

Nonalcoholic Steato-hepatitis Associated with Childhood Obesity

Gastroenterology and Nutrition| August 01 2000 Nonalcoholic Steato-hepatitis Associated with Childhood Obesity AAP Grand Rounds (2000) 4 (2): 11. https://doi.org/10.1542/gr.4-2-11 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Nonalcoholic Steato-hepatitis Associated with Childhood Obesity. AAP Grand Rounds August 2000; 4 (2): 11. https://doi.org/10.1542/gr.4-2-11 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: childhood obesity, hepatitis, steatohepatitis, non-alcoholic, obesity Source: Rashid M, Roberts EA.Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2000;30:48–53. Non-alcoholic steatohepatitis (NASH) occurs commonly in adults in association with obesity, hyperlipidemia, and adult onset diabetes mellitus1 and is known to be a cause of hepatic fibrosis and cirrhosis.2,3 The natural history and clinical presentation of NASH in children and adolescents is unknown. Rashid and Roberts report their 10-year experience of 36 children (21 male, 15 female) diagnosed with NASH. The median age was 12 years with a range of 4–16 years of age. Thirty patients (83%) were obese, with a mean weight of 147% of ideal body weight. Two patients had diabetes mellitus at the time of diagnosis, while 2 more later developed diabetes mellitus. Thirteen of 36 (36%) had acanthosis nigricans (all but one was obese). Thirty-three of 36 patients (92%) had elevated ALT values (mean 179 +/− 31 U/L with normal <40 U/L) although none of the 36 patients had signs or symptoms of chronic liver disease. Hypercholesterolemia (7/36) and hypertriglyc-eridemia (11/36) were relatively common features of NASH. Hepatic ultrasound was obtained in 31 patients, and 24 (77%) showed abnormalities including hepatomegaly and increased echogenicity suggestive of fatty infiltration. Liver biopsy was performed in 24 patients and all patients had significant macrovesicular lipid deposition. Inflammation was present in 88%, and fibrosis/cirrhosis in 75%. One 10-year-old patient had significant cirrhosis noted at biopsy. There were no predictive indicators separating the fibrosis/cirrhosis group from those children who did not have fibrosis at time of biopsy. In the follow-up of 21 patients it was noted that 6 patients lost weight and all of these patients had improvements in the AST level with normalization of values in 2 patients. This report is a sobering reminder that obesity may be associated with the potentially life-threatening consequences of NASH although the long-term prognosis in children with this disorder remains unknown. The presence of hepatomegaly, hyperglycemia, abnormal liver enzymes, acanthosis nigricans, hyperlipidemia, and/or an abnormal hepatic ultrasound in an obese child/adolescent should prompt consideration of liver biopsy and aggressive dietary and behavioral/lifestyle intervention to lose weight. Several “take-home” messages need to be heeded: 1) obesity-associated NASH does occur in children and may be associated with significant liver disease; 2) acanthosis nigricans is a cutaneous marker of potential hyperinsulinemia and may be associated with NASH; 3) an abnormal ultrasound of the liver (enlargement and/or increased echogenicity) in an obese patient should trigger consideration of NASH; 4) an abnormal liver ultrasound cannot separate those patients with and without hepatic fibrosis/cirrhosis – only a liver biopsy can do this; 5) liver enzymes do not predict fibrosis and/or cirrhosis in patients with NASH; 6) weight loss can improve obesity-associated NASH; 7) although NASH does occur in non-obese children, its prevalence is increased in obesity and should be considered in all obese children. This report provides further evidence supporting aggressive therapeutic measures with respect to early weight control in children. Although only a small number of... You do not currently have access to this content.