Liver Disease In Children Research Articles

Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: relation to transient elastography with controlled attenuation parameter.

Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Visfatin is an adipokine produced by visceral fat tissue and liver cells. Transient elastography with controlled attenuation parameter (CAP) noninvasively assesses liver fibrosis and steatosis. To measure visfatin level in 80 children and adolescents with obesity as a potential biomarker for NAFLD and assess its relation to transient elastography. Abdominal ultrasound, liver stiffness and CAP measurements were performed for all patients. Fasting lipid profile, fasting blood glucose, insulin level, liver and kidney functions, coagulation profile and serum visfatin levels were assessed. Among patients with obesity, 31 (38.8%) had NAFLD and 16 (20%) patients had elevated alanine aminotransferase (ALT), while 9 (11.2%) had both NAFLD and elevated ALT. Transient elastography showed that 12.5% had fibrosis stage F1, 2.5% had F2 and another 2.5% had F3 while none had F4. Using CAP, 23.8, 13.8 and 17.5% had S1, S2 and S3, respectively. Serum visfatin levels were significantly elevated in all patients compared with nonobese controls. Higher visfatin levels were found among patients with dyslipidemia, NAFLD, elevated ALT and steatosis defined by CAP. Serum visfatin was related to the degree of fibrosis and steatosis. Visfatin cutoff value 18 ng/mL could significantly detect the presence of NAFLD with 83.9% sensitivity and 81.4% specificity. Serum visfatin was positively correlated to BMI, waist circumference, waist/hip ratio, ALT, total cholesterol, liver stiffness and CAP. Visfatin could be a promising serum biomarker for monitoring liver disease among pediatric patients with obesity.

A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo.

Alpha 1-antitrypsin deficiency (AATD) is the most common genetic cause of liver disease in children and is associated with early-onset chronic liver disease in adults. AATD associated liver injury is caused by hepatotoxic retention of polymerized mutant alpha 1-antitrypsin molecules within the endoplasmic reticulum. Currently, there is no curative therapy for AATD. In this study, we selected small molecules with the potential to bind mutant alpha 1-antitrypsin (Z-variant) to inhibit its accumulation in hepatocytes. We used molecular docking to select candidate compounds that were validated in cell and animal models of disease. A crystal structure of polymerized alpha 1-antitrypsin molecule was used as the basis for docking 139,735 compounds. Effects of the top scoring compounds were investigated in a cell model that stably expresses Z-variant alpha 1-antitrypsin and in PiZ mice expressing Z-variant human alpha 1-antitrypsin (Z-hAAT), encoded by SERPINA1*E342K. 4′,′5-(Methylenedioxy)-2-nitrocinnamic acid was predicted to bind cleaved alpha 1-antitrypsin at the polymerization interface, and observed to co-localize with Z-hAAT, increase Z-hAAT degradation, inhibit intracellular accumulation of Z-hAAT, and alleviate liver fibrosis.

Non-alcoholic fatty liver disease in children: pathogenesis and diagnostic and therapeutic possibilities

Non-alcoholic fatty liver disease in children: pathogenesis and diagnostic and therapeutic possibilities

КЛАСИФІКАТОР СТАНУ ПЕЧІНКИ У ДІТЕЙ З ПАТОЛОГІЄЮ ГЕПАТОБІЛІАРНОЇ СИСТЕМИ ЗА ТЕКСТУРНИМИ СТАТИСТИКАМИ УЛЬТРАЗВУКОВОГО ДОСЛІДЖЕННЯ

With the results of ultrasound diagnostics of the liver, it is possible to diagnose the presence of diffuse liver diseases. At the entrance it was received a set of medical images of ultrasound diagnostics of the liver. In this work, texture analysis methods were applied to the images, therefore it was received 96 statistical features. All received data were brought to the standard distribution. The number of attributes has been reduced while retaining significant information through the principal component analysis. The construction of the classifier model is considered, the comparison of the efficiency of the model of random forest, logistic regression and multilayer perceptron is given. The accuracy of the model was evaluated using the cross-validation. The best result got the model of multivariate logistic regression - 77%. The system for prediction of possible liver disease in children is developed with the help of texture analysis of the results of sonography. The obtained system visualizes the results of prediction and their accuracy in order to simplify the decision-making process of the ultrasound diagnostics doctor

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

BackgroundToxicant-associated steatohepatitis has been described in adults but less is known regarding the role of toxicants in liver disease of children. Perfluoroalkyl substances (PFAS) cause hepatic steatosis in rodents, but few previous studies have examined PFAS effects on severity of liver injury in children. ObjectivesWe aimed to examine the relationship of PFAS to histologic severity of nonalcoholic fatty liver disease (NAFLD) in children. MethodsSeventy-four children with physician-diagnosed NAFLD were recruited from Children’s Healthcare of Atlanta between 2007 and 2015. Biopsy-based liver histological features were scored for steatosis, lobular and portal inflammation, ballooning, and fibrosis. Plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS), and untargeted plasma metabolomic profiling, were determined using liquid chromatography with high-resolution mass spectrometry. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with PFAS. A structural integrated analysis was applied to identify latent clusters of children with more severe form of NAFLD based on their PFAS levels and metabolite pattern. ResultsPatients were 7–19 years old, mostly boys (71%), Hispanic (51%), and obese (85%). The odds of having nonalcoholic steatohepatitis (NASH), compared to children with steatosis alone, was significantly increased with each interquartile range (IQR) increase of PFOS (OR: 3.32, 95% CI: 1.40–7.87) and PFHxS (OR: 4.18, 95% CI: 1.64–10.7). Each IQR increase of PFHxS was associated with increased odds for liver fibrosis (OR: 4.44, 95% CI: 1.34–14.8), lobular inflammation (OR: 2.87, 95% CI: 1.12–7.31), and higher NAFLD activity score (β coefficient 0.46; 95% CI: 0.03, 0.89). A novel integrative analysis identified a cluster of children with NASH, characterized by increased PFAS levels and altered metabolite patterns including higher plasma levels of phosphoethanolamine, tyrosine, phenylalanine, aspartate and creatine, and decreased plasma levels of betaine. ConclusionsΗigher PFAS exposure was associated with more severe disease in children with NAFLD. PFAS may be an important toxicant contributing to NAFLD progression; however larger, longitudinal studies are warranted to confirm these findings.

Genetic variation and biological information analysis of lipid metabolism associated with non-alcoholic fatty liver disease in children

Objective To fully investigate the roles of gene variations associated with lipid metabolism in pediatric non-alcoholic fatty liver disease(NAFLD). Methods One hundred obese children who were admitted to the gastroenterology department of Shenzhen Children′s Hospital from September 2017 to September 2018 meeting the inclusion criteria were collected.There were 66 males and 34 females aged 8-18 years.Exon sequencing was performed on blood samples from 100 subjects including 39 children with NAFLD(NAFLD group) and 61 healthy obese children(control group). The mutations of genes in lipid metabolism were investigated, and the functions of the variants were further evaluated through PPI analysis and Go term enrichment analysis and software tools which could predicts possible impact on the structure and function of proteins. Results There were no significant differences between NAFLD and control group in gender and age(all P>0.05). Body mass index(BMI) and waist in the control group were significantly lower than those of NAFLD group(all P C, chr4: 100510903: A>G) located in MTTP were significantly differently distributed between 2 groups(all P=0.002), and a potential pathogenic mutation could exist in rs2306986 site. Conclusions The findings of this study indicate that lipid metabolism plays an important role in NAFLD and rs2306986 in MTTP was associated with higher susceptibility to NAFLD. Key words: Child; Non-alcoholic fatty liver disease; Genetic variation; Lipid metabolism; Biological information

Diagnosis and treatment of non-alcoholic fatty liver disease in children

Non-alcoholic fatty liver disease (NAFLD) is a chronic steatosis of the liver in children and adolescents under 18 years of age.It is closely related to insulin resistance and genetic susceptibility.Its clinical symptoms are often non-specific.Diagnosis mainly depends on imaging findings and laboratory tests.Liver biopsy is the golden standard , but it is not a routine approach because of its traumatic nature.NAFLD in children should be distinguished from other hereditary metabolic diseases and liver diseases that can cause liver steatosis.At present, diet and exercise therapy are its first-line treatment.In addition, hepatoprotective therapy, improvement of insulin resistance and hyperlipidemia, vitamin E, probiotics are also gradually attracting attention. Key words: Non-alcoholic fatty liver disease; Diagnosis; Treatment; Child

1146 The Use of Liver Biopsy to Determine the Severity of Nonalcoholic Fatty Liver Disease in Children Across the United States

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease. Determining the severity of NAFLD using the presence of nonalcoholic steatohepatitis (NASH) and stage of liver fibrosis is important, yet liver biopsy remains the gold standard despite limitations to its use. This study surveyed pediatric gastroenterologists across the United States to determine which guidelines are used to determine the severity of NAFLD in children, which patients undergo liver biopsy, and how these guidelines compare to each other and to clinical practice. METHODS: 140 pediatric gastroenterologists were surveyed electronically regarding current diagnostic practices for NAFLD. Responses were reviewed in Survey Monkey and compared to current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), American Association for the Study of Liver Diseases (AASLD) and European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines regarding liver biopsy for evaluation of NAFLD. RESULTS: 140 surveys were distributed with 54 responses, a 38.6% response rate. Participants included pediatric gastroenterologists, hepatologists and transplant hepatologists. 96.2% reported familiarity with NASPGHAN guidelines, 22.6% with ESPGHAN and 39.6% with AASLD. 88.7% of responders desired a generalized consensus regarding proper diagnosis. Pediatric gastroenterologists referred obese patients with abnormal liver enzymes suspected to have NAFLD 22% of the time, pediatric hepatologists 27.2%, and transplant hepatologists 39.9% (one-way ANOVA with P-value of 0.324). 61.5% of responders reported using Fibroscan and 59.6% used MR elastography to assess severity of NAFLD and presence of liver fibrosis when not pursuing liver biopsy. 92.5% of responders believed the presence of autoimmune antibodies was important in deciding when to proceed to liver biopsy, as well as 88.7% using abnormal screening labs and 75.5% using imaging suggestive of liver fibrosis. CONCLUSION: Comparison between the criteria that providers believed warranted a liver biopsy versus those included in society guidelines differed. The presence of autoimmune antibodies, abnormal screening labs, and liver fibrosis suggested on imaging all appeared to be important factors regardless of current guidelines. Providers also seem to rely on Fibroscan and MR elastography over liver ultrasound despite the lack of validated cutoff values in children.

Does Urinary Thiodiglycolic Acid Increase the Risk of Non-Alcoholic Fatty Liver Disease in Children Living Near a Petrochemical Complex?

Does Urinary Thiodiglycolic Acid Increase the Risk of Non-Alcoholic Fatty Liver Disease in Children Living Near a Petrochemical Complex?

The role of elastography in the assessment of chronic liver disease in children.

Conventional ultrasonography is a method preferred for the investigation of chronic liver diseases in pediatric groups, as it is non-invasive, cheap, feasible and available. The purpose of this study is to present the role of Share-wave Elastography (SWE) in terms of diagnostic value in children diagnosed with "chronic liver disease." We studied patients who had been diagnosed with chronic liver disease between March 2012-September 2015, and who had undergone liver biopsy and had their pathology results, compared with 26 healthy subjects. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 20.0. "Pearson Correlation Analysis" was performed in order to measure the relationship between elastography values and Brunt level. This study had 107 subjects in total, consisting of 81 patients between 0-204 months of age Pearson correlation coefficient level was determined as r = 0.644. Since the correlation coefficient is positive, there is a same-directional relationship between Elastography level and Brunt degree. This means that while one of the variables is increasing, the other one will also increase. Since it is known that development of hepatic fibrosis is a dynamic process, and that many hepatic fibrosis etiologies are known to continue throughout the course of life, the application of Real time SWE method instead of repeated liver biopsies on patients is a much simpler and smart method. Increasing the clinical use of Real Time SWE method with future studies might provide an opportunity for preventing unnecessary liver biopsies since the patients are evaluated in a shorter time and in a cost-effective manner.

INFLUENCE OF GASTROINTESTINAL HORMONES ON THE DEVELOPMENT OF OBESITY AND NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

Obesity is becoming a global epidemic among children, and the social significance of this problem is determined by the threat of disability of young patients, reducing life expectancy and the development of severe comorbidities. As a result of the increasing number of studies on energy homeostasis, it has been suggested that obesity is a multifactorial and more complex disease than previously thought. In recent years, the attention of researchers is increasingly attracted to the study of intestinal microbiota and its impact on human health, due to the development of new technologies and methods of studying the microbiome. Recent studies have shown that there is a mutual influence of the brain and intestines on each other, and there is increasing evidence that confirms the role of this complex relationship in the regulation of hunger, satiation and energy balance. It is proved that there is a direct impact on these processes of intestinal microbiota, and mediated through its intervention in the synthesis and metabolism of hormones and biologically active compounds of the digestive system. Today it is known that the gastrointestinal tract is one of the human organs where the most hormones are synthesized. At the present stage of development of science, it is known that there are more than 30 gastrointestinal hormones and biologically active substances that regulate the processes of digestion and participate in the regulation of general homeostasis. The most important role in the development of obesity and non-alcoholic fatty liver disease belongs to hormones such as ghrelin, peptide YY and glucagon-like peptide 1. The literature review presents current data that demonstrate the role of gastrointestinal hormones in the formation and development of obesity and non-alcoholic fatty liver disease in children as well as data of own research.

Development of a Plasma Screening Panel for Pediatric Nonalcoholic Fatty Liver Disease Using Metabolomics.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children, but diagnosis is challenging due to limited availability of noninvasive biomarkers. Machine learning applied to high‐resolution metabolomics and clinical phenotype data offers a novel framework for developing a NAFLD screening panel in youth. Here, untargeted metabolomics by liquid chromatography–mass spectrometry was performed on plasma samples from a combined cross‐sectional sample of children and adolescents ages 2‐25 years old with NAFLD (n = 222) and without NAFLD (n = 337), confirmed by liver biopsy or magnetic resonance imaging. Anthropometrics, blood lipids, liver enzymes, and glucose and insulin metabolism were also assessed. A machine learning approach was applied to the metabolomics and clinical phenotype data sets, which were split into training and test sets, and included dimension reduction, feature selection, and classification model development. The selected metabolite features were the amino acids serine, leucine/isoleucine, and tryptophan; three putatively annotated compounds (dihydrothymine and two phospholipids); and two unknowns. The selected clinical phenotype variables were waist circumference, whole‐body insulin sensitivity index (WBISI) based on the oral glucose tolerance test, and blood triglycerides. The highest performing classification model was random forest, which had an area under the receiver operating characteristic curve (AUROC) of 0.94, sensitivity of 73%, and specificity of 97% for detecting NAFLD cases. A second classification model was developed using the homeostasis model assessment of insulin resistance substituted for the WBISI. Similarly, the highest performing classification model was random forest, which had an AUROC of 0.92, sensitivity of 73%, and specificity of 94%. Conclusion: The identified screening panel consisting of both metabolomics and clinical features has promising potential for screening for NAFLD in youth. Further development of this panel and independent validation testing in other cohorts are warranted.

The Liver in Children With Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) is recognized as an emerging health risk in obese children and adolescents. NAFLD represents a wide spectrum of liver conditions, ranging from asymptomatic steatosis to steatohepatitis. The growing prevalence of fatty liver disease in children is associated with an increased risk of metabolic and cardiovascular complications. NAFLD is considered the hepatic manifestation of Metabolic Syndrome (MetS) and several lines of evidence have reported that children with NAFLD present one or more features of MetS. The pathogenetic mechanisms explaining the interrelationships between fatty liver disease and MetS are not clearly understood. Altough central obesity and insulin resistance seem to represent the core of the pathophysiology in both diseases, genetic susceptibility and enviromental triggers are emerging as crucial components promoting the development of NAFLD and MetS in children. In the present review we have identified and summarizied studies discussing current pathogenetic data of the association between NAFLD and MetS in children.

Urinary thiodiglycolic acid is associated with increased risk of non-alcoholic fatty liver disease in children living near a petrochemical complex

BackgroundOccupational and experimental studies have revealed that high vinyl chloride monomer (VCM) exposure is associated with non-alcoholic fatty liver disease (NAFLD). Epidemiological study reported that children living near a petrochemical complex have elevated exposure levels of urinary thiodiglycolic acid (TDGA), a potential VCM biomarker. However, no studies on the association of urinary TDGA exposure with NAFLD in children are available. AimTo assess the association of pediatric NAFLD with urinary TDGA exposure in school-aged children living near a petrochemical complex. Materials and methodsIn total, 261 school-aged children (aged 6–13 years) living near a petrochemical complex were recruited during October 2013 to September 2014. First morning spot urine was sampled for analyzing urinary TDGA through liquid chromatography-tandem mass spectrometry. Ultrasonography and serum alanine aminotransferase (ALT) were examined in each participant. NAFLD was diagnosed as recommended by the North American and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN). Risk for NAFLD with urinary TDGA exposure in children was evaluated using a multivariate logistic regression model. ResultsThe percentage of children with NAFLDNASPGHAN and NAFLDESPGHAN were 9.6% and 11.5%, respectively. Median levels (μg/g creatinine) of urinary TDGA of children with NAFLDNASPGHAN (vs non-NAFLDNASPGHAN) and NAFLDESPGHAN (vs non-NAFLDESPGHAN) were 118.0 (vs 96.6) and 113.1 (vs 96.5), respectively. Participants in the highest urinary TDGA quartile (Q4: ≥160.0 μg/g creatinine) had a significantly increased risk (odds ratio [OR] = 4.95; 95% confidence interval [CI] = 1.15–21.38; P = 0.032) and dose-response trend (Ptrend = 0.045) for NAFLDNASPGHAN compared with those in the lowest urinary TDGA quartile (Q1: <35.4 μg/g creatinine) after adjustment for age, gender, BMI, triglycerides, HOMA-IR and distance of elementary schools from the petrochemical complex. Participants in the Q4 had borderline significantly increased risk (OR = 3.45; 95% CI = 0.89–13.42; P = 0.074) correlated with NAFLDESPGHAN compared with those in the Q1 after adjustment for confounders. ConclusionOur findings support the hypothesis that children exposed to higher urinary TDGA levels significantly increased pediatric NAFLD risk. Serum ALT levels can be a useful predictor for screening children's NAFLD in field studies. Large and longitudinal studies are warranted to elucidate the association.

NAFLD in children: new genes, new diagnostic modalities and new drugs.

Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children and adolescents. Over the past 5 years, developments have revolutionized our understanding of the genetic factors, natural history, diagnostic modalities and therapeutic targets for this disease. New polymorphisms, such as those in PNPLA3, TM6SF2, MBOAT7 and GCKR, have been identified and used to predict the development and severity of NAFLD in both adults and children, and their interaction with environmental factors has been elucidated. Studies have demonstrated the true burden of paediatric NAFLD and its progression to end-stage liver disease in adulthood. In particular, nonalcoholic steatohepatitis can progress to advanced fibrosis and cirrhosis, emphasizing the importance of early diagnosis. Non-invasive imaging tests, such as transient elastography, will probably replace liver biopsy for the diagnosis of nonalcoholic steatohepatitis and the assessment of fibrosis severity in the near future. The therapeutic landscape is also expanding rapidly with the development of drugs that can modify liver steatosis, inflammation and fibrosis, indicating that pharmacotherapy for NAFLD will become available in the future. In this Review, we summarize current knowledge and new advances related to the pathogenesis and management of paediatric NAFLD.

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.

Metabolomic Characterization of a Novel Pig Model of Pediatric Non-alcoholic Fatty Liver Disease (P08-131-19)

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is a leading nutrition-linked liver disease in children. We have recently identified the neonatal Iberian pig as a novel model of pediatric NAFLD. Interestingly, feeding a high fructose-high fat (HFF) diet to neonatal Iberian pigs for 10 weeks did not induce obesity and decreased high and low density lipoproteins in serum, while the liver exhibited many of the histological features of pediatric NAFLD. In this study we utilized a metabolomics approach to characterize the metabolic phenotype of this pig model. MethodsPlasma and liver samples collected from Iberian pigs fed control, HFF, control + probiotic and HFF + probiotic diets were analyzed by LC-MS using targeted assays for primary metabolomics, aminomics, and lipidomics. Data was analyzed with multivariate statistics and 2-way ANOVA with t-tests adjusted for false discovery rate. ResultsResults from multivariate tests indicated no diet × probiotic interaction or probiotic effect, so only the main effect of diet is shown. A total of 224 and 218 metabolites were identified in the plasma and liver, respectively. In agreement with previous NAFLD models, the HFF diet increased hepatic branched chain amino acids, cholesteryl esters, hydroxyproline, plasma acylcarnitines and primary bile acids, and altered hepatic triacylglycerol-species composition (P < 0.0001). In addition, HFF pigs had increased homocysteine and methionine levels combined with a decrease in pyridoxate in liver (P < 0.0001), suggesting a disruption in the one carbon cycle and its methyl donation capability. HFF decreased hepatic choline and betaine (P < 0.0001), which may indicate a compensatory use of the methyl groups of these compounds. The aforementioned reduction of choline used for the CDP-choline pathway and the potential one carbon cycle impact on SAM availability for the phosphatidylethanolamine N-methyltransferase (PEMT) pathway may explain the observed differential changes in hepatic phosphatidylcholines (P < 0.0001), which are required for the production of very low density lipoproteins (VLDL). ConclusionsUnique features of this model such as reduced plasma lipoproteins and lack of weight gain in the presence of hepatic steatosis may be related to an altered one carbon cycle impacting phosphatidylcholine production. Funding SourcesARI, AcornSeekers.

P312 Long-term follow-up of liver disease in children and young people with cystic fibrosis in the UK

P312 Long-term follow-up of liver disease in children and young people with cystic fibrosis in the UK

Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population

Introduction and ObjectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD. MethodsWe included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender. ResultsThe mean age was 10.64±2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR=2.39; 95%CI=1.10–5.19; p=0.025). For girls, NAFLD was significantly associated with triglycerides (p=0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p=0.048), and the visceral adiposity index (VAI) (p=0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p=0.001), waist circumference (WC) (p<0.001), HDL cholesterol (p=0.021), alanine aminotransferase (ALT) (p<0.001), and aspartate aminotransferase (AST) (p=0.002). ConclusionsIn our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5U/L in females and 27.5U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.

Histopathology findings of chronic liver diseases in pediatric age group

Objectives: Early and accurate diagnosis of Chronic liver diseases (CLD) in children is very important as it is associated with major cause of mortality and morbidity. Though, nowadays most advanced and ancillary diagnostic techniques are available, Liver biopsy still plays a very important role in diagnosis of chronic liver diseases in children. The present study is aimed to study the role of liver biopsy in diagnosis of various chronic liver diseases in children and to evaluate the histopathologic findings of various liver and hepatobiliary diseases in children. Materials and Methods: This was a prospective study carried out in a large teaching hospital. Total 55 children in pediatric age group (1-12yrs) who presented with chronic liver disease were subjected to liver biopsy. Relevant investigations were done. The procedure was carried out under all aseptic condition after obtaining a written informed consent of the patient’s parents. The liver biopsy procedure was done through two approaches one percutaneous and second is transjugular approach. The second approach was used in patients with deranged PT/PI, to avoid the risk of internal bleeding. The biopsy piece was collected in formalin and sent to histopathology for analysis. An expert pathologist was identified for the study of these biopsy pieces. The biopsy findings were evaluated. Results: In our study the incidence of CLD was high in 6-12 yr of age group (34.34%) with a male predominance (60%). In our study the most common presenting complaint was jaundice and abdominal distension (38.18%) followed by jaundice alone (34.54%). Liver biopsy demonstrated various histopathological abnormalities like inflammation (80%) followed by ballooning of hepatocytes (74.54%). Other findings included cholestasis /necrosis/fibrosis/glycogenation/special stains positivity/cirrhosis. The incidence of cirrhosis on liver biopsy was41.81%.We diagnosed maximum cases of Wilson’s disease 12 out of which 9 patients had cirrhos