Nonalcoholic Fatty Liver Disease In Children Research Articles

Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine

ABSTRACT Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases).

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.

Separating the effects of early and later life body mass index on liver diseases: A Mendelian randomization study

Background and aimThe independent effects of childhood and adult body mass index (BMI) on non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC) are lacking assessment. We aimed to separate the effects of childhood and adult BMI on NAFLD, cirrhosis, and HCC. MethodsGenetic variants associated with childhood and adult BMI were selected as instrumental variables. Two-sample univariable and multivariable MR estimated the total and direct effect of childhood and adult BMI on NAFLD, cirrhosis, and HCC. ResultsGenetically predicted each 1-SD increased childhood BMI (OR = 1.30, 95 % CI = 1.12 to 1.51, P = 0.001) and adult BMI (OR = 1.57 95 % CI = 1.33 to 1.84, P = 5.49E-08) was associated with an increased risk of NAFLD. The association between childhood BMI (OR = 0.97, 95 % CI = 0.77 to 1.24, P = 0.825) and NAFLD did not remain significant after adjusting for adult BMI (OR = 1.64, 95 % CI = 1.23 to 2.20, P = 0.001). The direct effects of childhood and adult BMI on cirrhosis and HCC were insignificant after considering their relationship. ConclusionMaintaining a normal BMI in adulthood significantly reduces the adverse effect of a higher childhood BMI on NAFLD. Further investigation is required to clarify the presence of this effect in cirrhosis and HCC.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study)

BackgroundThe increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD.MethodsThis is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8–10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students’ body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted.DiscussionThe program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children.Trial registrationClinicaltrials.gov NCT05482191. Registered on July 2022.

Role of intestinal flora in the development of nonalcoholic fatty liver disease in children.

In China, 45% of adolescents with obesity develop fatty liver disease, a condition that increases the long-term risk of developing cirrhosis and liver cancer. Although the factors triggering nonalcoholic fatty liver disease (NAFLD) vary in children, the composition of intestinal microflora has been found to play an increasingly important role. However, evidence is limited on the prevalence of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in Chinese children. Therefore, this study aimed to evaluate the fecal microbiome of Chinese children with NAFLD and further analyze the potential of flora in regulating NAFLD-related symptoms and metabolic functions. Specifically, the study applied a 16S rRNA and metagenomic sequencing to the fecal samples of pediatric patients with NAFLD, NASH, and NAFL, as well as healthy controls, to explore the correlation among NAFLD-related indexes, metabolic pathways, and gut flora. The findings showed that some fecal microbiota had a negative correlation with body mass index, and various NAFLD-related bacteria, including Lachnoclostridium, Escherichia-Shigella, and Faecalibacterium prausnitzii, were detected. Consequently, the study concluded that the variation in gut microbiota might be more important in improving NAFLD/NASH compared with single species, providing a microbiota diagnostic profile of NAFLD/NASH.IMPORTANCEThis study aims to characterize the gut microbiota in Chinese children with nonalcoholic fatty liver disease (NAFLD) through 16S rRNA and metagenomic sequencing. The results highlight the association between fecal microbiota and NAFLD in Chinese children, demonstrating distinct characteristics compared to adults and children from other countries. Based on the sequencing data from our cohort's fecal samples, we propose a microbiota model with a high area under the curve for distinguishing between NAFLD and healthy individuals. Furthermore, our follow-up study reveals that changes in the relative abundance of microbial biomarkers in this model are consistent with variations in patients' body mass index. These findings suggest the potential utility of the microbiota model and microbial biomarkers for diagnosing and treating NAFLD in children.

Increased prevalence of metabolic syndrome and non-alcoholic fatty liver disease in children with atopic dermatitis: A case-control study from northern India.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects children worldwide, with potential associations to metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Limited research exists on the interplay between AD, MetS, and NAFLD in the pediatric population. This study aimed to investigate the prevalence and potential relationships among AD, MetS, and NAFLD in children. A case-control study design was employed, recruiting 50 children with AD (median age: 9.5 years) and 50 age- and sex-matched healthy controls (median age: 11.5 years, p = .051). Data on demographic characteristics, clinical features, disease severity, treatment history, anthropometric measurements, and laboratory evaluations were collected. MetS and NAFLD were diagnosed based on established criteria. The prevalence of MetS was significantly higher in children with AD compared with controls (24% vs. 2%, p = .002). Significant differences for systolic blood pressure (p < .001), diastolic blood pressure (p = .012), and waist circumference (p = .040) were observed between AD patients and controls. Children with AD had higher triglyceride levels (p = .005). NAFLD was exclusively seen in moderate to severe AD cases (6% vs. 0%, p = .242). AD severity showed associations with increased body mass index (p = .020). This study highlights the increased prevalence of MetS and the potential association with NAFLD in children with AD. The findings suggest that AD may contribute to the development of metabolic abnormalities at an early age. Further research is needed to elucidate the underlying mechanisms and explore preventive strategies for these interconnected conditions.

The epidemiological characteristics of liver disease in hospitalized children: a 10-year single-center retrospective study.

This investigation aimed to examine the epidemiological characteristics of children with liver disease hospitalized for the first time between June 2012 and May 2022 in a tertiary hospital. The study retrospectively recruited children aged between 29 days and 18 years who had been hospitalized for liver disease. Clinical characteristics were categorized by age and etiology, and time trends were assessed using linear regression analysis. A total of 4,313 children were recruited, with a median age of 0.7 (0.2-4.5) years, and 54.5% of the cases were in the 0-1 years age group. Infection was the primary cause of liver disease (30.0%), followed by undiagnosed cases (25.8%), biliary obstructive disease (15.9%), inherited metabolic liver disease (13.9%), and non-alcoholic fatty liver disease (NAFLD) (3.2%). Genetic diagnoses were established in 43.9% (478/1,088) of patients. The percentage of NAFLD demonstrated an upward trend from 1.2% in 2012 to 12.6% in 2022 (p = 0.006). In contrast, the percentage of cytomegalovirus hepatitis decreased from 13.3% in 2012 to 3.4% in 2022 (p = 0.002). Liver disease in infancy makes up the largest group in pediatric liver disease. Infection remains the leading cause of pediatric liver disease. Hospital admissions for NAFLD in children have increased rapidly over the past decade, while cytomegalovirus hepatitis has declined markedly.

THU146 Triglyceride Glucose Index Is Superior To The Homeostasis Model Assessment Of Insulin Resistance For Predicting Severity Of Nonalcoholic Fatty Liver Disease In Korean Children And Adolescents

Abstract Disclosure: J. Yoon: None. E. Kim: None. Background: Triglyceride glucose (TyG) index is known as a reliable insulin resistance surrogate marker to identify non-alcoholic fatty liver disease (NAFLD). Ultrasonographic fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in patients with NAFLD and accurately identifies histological severity. Few studies have compared the TyG index to homeostasis model assessment of insulin resistance (HOMA-IR) in the detection of NAFLD in children and adolescents. Additionally, there were no studies comparing the ability of TyG index and HOMA-IR to assess the severity of NAFLD. Objects: Therefore, we investigated the relationship between TyG index and NAFLD compared to HOMA-IR in identifying and assessing the severity of NAFLD in children and adolescents. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (&amp;gt;26IU/L in boys and &amp;gt;22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The US-FLI was significantly correlated with TyG index (r=0.264, p=0.003) but not with HOMA-IR after controlling for sex, age, and BMI. Multiple linear regression analysis showed that TyG index were significantly associated with US-FLI (β=0.202, p=0.002) not with HOMA-IR after controlling for sex, age, and BMI. The TyG index was superior to HOMA-IR in its ability to detect the severity of NAFLD in US-FLI ≥4, ≥5, and ≥6. Conclusions: Both TyG index and HOMA-IR were useful for detecting pediatric NAFLD. However, the TyG index was useful for detecting the severity of NAFLD, whereas HOMA-IR was not. Therefore, we propose to use the TyG index to predict and evaluate the severity of NAFLD in children. Presentation: Thursday, June 15, 2023

Association of single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most unabating cause of chronic liver disease in children and adolescents. The aim of this study was to examine the association of paediatric NAFLD and single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene. ­Methods:Τhis case-control study was carried out from June 2021 to December 2022. A total of 51 overweight children aged 6  17 years were recruited in this study and divided into NAFLD (cases) and non-NAFLD (controls) groups on the basis of hepatic steatosis detected by liver ultrasonography. We analyzed the rs738409 polymorphism by TaqMan assay and examined its association with NAFLD. ­­­­­Results: A total of 31 (60.7%) children were in case group and 20 children were in control group. Body mass index, waist circumference, total cholesterol and triglycerides levels were statistically higher in NAFLD group. Homogygosity (GG status) and heterogygosity (CG status) for PNPLA3 polymorphism was seen in 2 (6.4%) and 18 (58.1%) children having NAFLD, respectively. PNPLA3 rs738409 genotypes were similar between case and control groups. Conclusion: No association was found between PNPLA3 rs 738409 SNP with the presence of NAFLD in children. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(3): 139-143

Analysis of risk factors for non-alcoholic fatty liver disease in hospitalized children with obesity before the late puberty stage.

This study aimed to determine the clinical characteristics of obese pediatric non-alcoholic fatty liver disease (NAFLD) in central China and verify the applicability of some known risk factors for pediatric NAFLD before late puberty. This was a retrospective case-control study. A total of 1,029 inpatients at Wuhan Children's Hospital before the late puberty stage were enrolled in the study, including 815 children with obesity (non-NAFLD group) and 214 children with obesity and NAFLD (NAFLD group) diagnosed by liver ultrasound. Subgroup analyses were performed according to sex and puberty. The anthropometric indices and laboratory test data of these 1,029 children were sorted. After intergroup comparison, a logistic regression model was used to determine the risk factors for pediatric NAFLD. Significant risk factors for NAFLD were further tested using receiver operating characteristic (ROC) curves to evaluate their ability to predict an early diagnosis of NAFLD. The NAFLD group had a mean age of 11.03 ± 1.66, with 11.18 ± 1.66 and 10.27 ± 1.45 years for male and female children, respectively (p < 0.05 and p < 0.01, respectively). Even subdivided by both sex and puberty, raised body mass index (BMI), homeostatic model-insulin resistance, triglycerides, alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γ-GT) were still found in the non-NAFLD and NAFLD groups (p < 0.05 and p < 0.01, respectively). The results of logistic regression analysis showed that BMI (odds ratio [OR], 1.468;95% confidence interval [CI], 1.356-1.590; p<0.001) and ALT (OR, 1.073;95%CI, 1.060-1.087; P<0.001) were two most independent risk factors for NAFLD. The maximal OR for BMI was 1.721 (95% CI, 1.336-2.217). In the female group, the maximal OR of ALT was found to be 1.104 (95% CI, 1.061-1.148). Age and thyroid-stimulating hormone (TSH) and γ-GT levels were also risk factors, but they appeared only in some groups. The results of the ROC analysis showed that ALT was a better predictor of pediatric NAFLD than BMI. The maximum area under the ROC curve in six of the nine groups belongs to ALT. BMI, ALT, and age are risk factors for NAFLD in children with obesity before late puberty. BMI had the greatest exposure risk for NAFLD, and ALT had the highest predictive value for the diagnosis of NAFLD. At the stratified level, for exposure risk, age was specific to the male sex, TSH was specific to the early puberty stage, and γ-GT was specific to the female sex plus the prepuberty stage. On a stratified level, for the female sex, even with age stratification, BMI rather than ALT has a better ability for the diagnosis of NAFLD.

The Prevalence of Non-Alcoholic Fatty Liver Disease in Iranian Children and Adult Population: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is the world's most common etiology of chronic liver disease. In this systematic review and meta-analysis, we estimated the prevalence of NAFLD in the Iranian children and adult population. A comprehensive search of five international databases, including PubMed, ISI/WOS, ProQuest, Scopus, and Google Scholar, was done from inception to Nov 2022. Studies on NAFLD patients and their risk factors were selected for meta-analysis. The quality of the included studies was assessed by The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for cross-sectional, and cohort studies. The heterogeneity between studies was investigated using Cochran test and I2 statistics. Random and fixed effect models were used for heterogenic and non-heterogenic studies, respectively. We used Comprehensive Meta-Analysis version 3 for conducting meta-analysis. Twenty studies were finally included. The total prevalence of NAFLD in children, boys, and girls was 6.7% (95% CI: 0.02-0.18), 12.5% (95% CI: 0.04-0.29) and, 10.1% (95% CI: 0.04-0.21), respectively. The total prevalence of NAFLD in obese children, obese boys, and obese girls was 42% (95% CI: 0.18-0.69), 44% (95% CI: 0.13-0.80), and 33 % (95% CI: 0.13-0.62), respectively. The total prevalence of NAFLD in adults was 36.9% (95% CI: 0.31-0.42). The prevalence of NAFLD in men and women was 33.8% (95% CI: 0.27-0.41) and 29.9% (95% CI: 0.21-0.40), respectively. NAFLD prevalence in Iranian adults and obese children is considerable; however, data about the children population was insufficient.

The relative contributions of soft tissue mass components as risk or protective factors of non-alcoholic fatty liver disease in children.

Several body components are known to be associated with non-alcoholic fatty liver disease (NAFLD) in children. However, the relative contributions of soft tissue mass components as risk or protective factors of NAFLD are largely unknown because measurements of these components are often highly correlated. Therefore, we aimed to estimate levels of association between soft tissue mass components and NAFLD. We collected the medical records of 555 Chinese children (aged 3-18 years). Five mutually exclusive and exhaustive components of soft tissue mass were measured using dual energy X-ray absorptiometry. NAFLD was diagnosed with abdominal B-ultrasound scan. We fit Dirichlet regression and multivariate linear regression models wherein age and NAFLD were used as predictors of the proportional measurements of soft tissue mass components. The proportion of android fat was significantly higher in children with NAFLD than in those without NAFLD (ratio of proportions ranged from 1.18 to 1.30), whereas proportions of trunk lean and limb lean were significantly lower (ratio of proportions ranged from 0.87 to 0.92 for trunk lean and from 0.82 to 0.91 for limb lean). The proportion of gynoid fat was slightly higher in boys with NAFLD than in those without NAFLD (ratio = 1.05), but this proportion was not significantly higher in girls. The association between the proportion of android fat and NAFLD appeared to be somewhat greater than the associations between proportions of trunk lean or limb lean components and NAFLD. Our findings suggest that lowering fat mass and increasing lean mass can both be used to combat NAFLD in children and that more studies are needed to determine the association between gynoid fat and NAFLD.

Combined effect of PNPLA3 rs738409 and UGT1A1 rs10929303 gene polymorphisms on nonalcoholic fatty liver disease in children

Objective: To investigate the combined effects of patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 (C > G) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) rs10929303 (C > T) on nonalcoholic fatty liver disease (NAFLD) in children and adolescents so as to provide scientific evidence for NAFLD genetic research. Methods: 1 027 children and adolescents aged 7-18 were selected as the research subjects. The general situation, past medical history, height and body weight measurements, and B- mode ultrasound test of the liver were investigated by dedicated full-time personnel. In addition, the morning fasting venous blood was collected to measure the blood biochemical indicators. DNA was extracted and genotyped for PNPLA3 rs738409 and UGT1A1 rs10929303. Logistic regression analysis was used to analyze the association and combined effect of the two gene polymorphisms and NAFLD. Statistical analysis was performed by t-test, Mann-Whitney U test, or c2 test according to different data. Results: The GG genotype of PNPLA3 rs738409 and the CC genotype of UGT1A1 rs10929303 were associated with an increased risk of developing NAFLD in children by 89% (OR = 1.89, 95% CI: 1.11-3.23, P = 0.019) and 96% (OR = 1.96, 95% CI: 1.21-3.17, P = 0.006), respectively, while the concurrent risk of NAFLD in those who carried the above two genotypes increased by 306% compared with those who did not carry both genotypes (OR = 4.06, 95% CI: 1.90 ~ 8.66, P < 0.001). Conclusion: The combined effect of PNPLA3 and UGT1A1 gene polymorphisms can significantly increase the risk of NAFLD in children, providing new evidence for elucidating the genetic susceptibility to NAFLD.

Is There any Need for the Early Detection of Non-alcoholic Fatty Liver Disease in Children with Type 1 Diabetes Mellitus?

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disorders worldwide. Regarding the shortage of evidence on NAFLD in type 1 diabetes mellitus (T1DM) and the importance of a thorough assessment of complications due to childhood diseases, this study aimed to assess the need for the early detection of NAFLD in children with T1DM. Methods: This cross-sectional study was conducted on 234 children with T1DM referred to 17 Shahrivar Hospital, Rasht, Iran. This study also assessed demographic characteristics, medical history, physical examination, laboratory tests, and hepatic ultrasound. The Mann-Whitney U and chi-square tests were used to compare the children with and without NAFLD. Additionally, univariate and multivariate logistic regressions were used to determine the predictors of NAFLD. Results: This study was conducted on 235 children with T1DM with a median age of 11.0 years (interquartile range (IQR): 8.0 - 14.0) and diabetes duration of 2.0 years (IQR: 1.0 - 4.0). The prevalence of NAFLD was estimated to be 10.2%. The children with NAFLD were significantly older (P = 0.016) and had a larger waist circumference (WC) z-score (P = 0.008) than those without NAFLD. Multiple logistic regression analyses showed that the odds of NAFLD increased with rising age (odds ratio (OR) = 1.29, 95% confidence interval (CI): 1.09 - 1.52) and WC z-score (OR = 2.39, 95% CI: 1.49 - 3.84). The cut-off point for the WC z-score was -0.025 (sensitivity = 58.3%, specificity = 72.0%). Conclusions: The NAFLD frequency in T1DM is relatively low (10.2%) and mainly consists of grade I fatty liver. The NAFLD screening should be further noticed in T1DM children with increasing age and WC as the predictors of NAFLD.

Shorter leukocyte telomere length protects against NAFLD progression in children

Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients. Using data from the Treatment of NAFLD in Children (TONIC) randomized controlled trial, we assessed the potential predictive relationship between LTL and liver disease progression based on two successive liver biopsies over 96 weeks. We assessed the potential relationship between LTL and child age, sex, and race/ethnicity and features of liver disease including components of histology. We subsequently evaluated predictors for improvement in non-alcoholic steatohepatitis (NASH) at 96 weeks including LTL. We also assessed predictors of lobular inflammation improvement at 96 weeks using multivariable models. Mean LTL at baseline was 1.33 ± 0.23 T/S. Increasing lobular and portal inflammation were associated with longer LTL. In multivariable models, greater lobular inflammation at baseline was associated with longer LTL (Coeff 0.03, 95% CI 0.006–0.13; p = 0.03). Longer LTL at baseline was associated with worsening lobular inflammation at 96 weeks (Coeff 2.41, 95% CI 0.78–4.04; p < 0.01). There was no association between liver fibrosis and LTL. The association between LTL and pediatric NASH does not parallel adults with no association between fibrosis stage and NASH. Conversely, longer LTL was associated with more lobular inflammation at baseline and increased lobular inflammation over the 96-week period. Longer LTL in children may indicate greater risk for future complications from NASH.

Relationship between obesity related indicators and non-alcoholic fatty liver disease in children: a systematic review and meta-analysis.

The incidence of childhood obesity is increasing. There is some controversy about the association between overweight and nonalcoholic fatty liver disease (NAFLD) in children. This article intends to compare the differences in these obesity related parameters between NAFLD children and healthy control children through meta-analysis to provide evidence-based medical evidence for clinical use. The literature were extracted from English and Chinese databases. Statistical analysis was performed using Stata/SE 16.0, IBM SPSS Statistics 26, and Review Manager 5.4 software. A total of 15 original case control studies were included, including 12 high-quality literature, 3 medium quality literature. The total sample size included in the analysis was 1,595 children, including 824 in the experimental group and 771 in the control group. The results of meta-analysis showed that the body mass index (BMI) of the NAFLD group was significantly higher than that of the control group [mean difference (MD) =1.05, 95% confidence interval (CI): 0.36-1.73]. Waist circumference of the NAFLD group was significantly larger than that of the control group (MD =1.66, 95% CI: 0.60-2.73). Triglyceride level in the NAFLD group was significantly higher than that in the control group (MD =1.08, 95% CI: 0.05-2.12). Low-density lipoprotein (LDL) level in the NAFLD group was significantly higher than that in the control group (MD =0.49, 95% CI: 0.12-0.85). In addition, fasting blood glucose of the NAFLD group was significantly higher than that of the control group (MD =0.31, 95% CI: 0.09-0.54) and insulin resistance index of the NAFLD group was significantly higher than that of the control group (MD =2.95, 95% CI: 1.41-4.49). Exercise had a significant effect on improving the degree of NAFLD in children [odds ratio (OR) =2.51, 95% CI: 1.83-3.43]. Various physical indicators were related to obesity, including BMI, waist circumference, triglyceride content, LDL, fasting blood glucose, and insulin resistance index, and all were significantly correlated with NAFLD in children, provided a reference for future clinical diagnosis and treatment work. In addition, exercise could significantly improve the degree of steatosis in children with NAFLD.

The Latest Evidence on the Association Between Vitamins and Non-alcoholic Fatty Liver Disease in Childhood

Context: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in children, with an increased incidence of overweight and obesity. Currently, no food and drug administration is approved for treating NAFLD in children; however, antioxidants such as vitamins are the safest options for managing this disease. Regarding the unknown aspects of managing NAFLD, this review provides an overview of the latest evidence on the association of vitamins A, B, C, D, and E with NAFLD in children and adolescents. Evidence Acquisition: In this narrative review, we searched and extracted relevant English publications from the Web of Science, PubMed, Scopus, and Google Scholar using keywords such as non-alcoholic fatty liver disease, NAFLD, children, pediatric, Vitamin A, Vitamin B, Vitamin C, Vitamin D, and Vitamin E. Results: The level of vitamins A, B, C, D, and E in children with NAFLD has been linked to the disease’s prognosis and severity. Conclusions: Regarding previous studies on this issue, measuring vitamins in children with NAFLD seems logical.

Circulating chemerin level and the risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Chemerin is participating in inflammation procedure and it has role in developing metabolic diseases. In the term of nonalcoholic fatty liver disease (NAFLD), the result of published studies are conflicting. So, in this study, the results of different studies investigating the relationship between chemerin level and NAFLD were summarized. The databases of PubMed, Scopus, Web of Science, and Embase were systematically searched until October 2022. The inclusion criteria were as follow: measured the mean chemerin level in adults and children with NAFLD and compared it with non-NAFLD population or reported the association between chemerin level and NAFLD. The methodological quality was assessed by the Joanna Briggs Institute (JBI) tool. The meta-analysis was done by STATA software. The pooled results were stated as the standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI). Sixteen studies were included in the systematic review, of which 13 studies remained for meta-analysis. The mean serum chemerin level was not significantly different between the groups [SMD: 0.52, 95% CI: -0.35, 1.39]. Moreover, there was no significant correlation between the chemerin level and NAFLD [OR: 1.01, 95% CI: 1, 1.02]. Besides, subgroup analysis indicated a significant correlation between serum chemerin level and NAFLD in children [OR: 1.02, 95% CI: 1.01, 1.03]. There were no significant differences in chemerin levels between the NAFLD and healthy adults; however, the association was significant in children. However, due to the lack of studies in this age group, the conclusion should be made with caution. The online version contains supplementary material available at 10.1007/s40200-023-01187-4.

Combination of the effect of ginger and anti-inflammatory diet on children with obesity with nonalcoholic fatty liver disease: A randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in children. Following earlier reports on an increase in the prevalence of childhood obesity, NAFLD is now becoming increasingly common in children. Although no definitive cure exists, early management, early diagnosis, and treatment can reduce its complications. This study aims to determine the effectiveness of the combination of ginger and an anti-inflammatory diet (AID) in children with obesity on fatty liver management. This randomized clinical trial was conducted on 160 children with obesity aged 8-11 years, with a mean (SD) weight of 65.01(9.67) kg, mean (SD) height of 139.87(7.37) cm, and mean (SD) body mass index of 33.40(5.59) kg/m2. The study duration was 12 weeks. Children were divided into four groups: ginger (G), AID, ginger plus an AID (GPA), and control. Ginger capsules comprised 1000 mg of ginger, whereas the AID comprised fruits and vegetables, fish, turkey, and chicken (without skin) with lean meat, omega-3 sources, nuts, legumes, probiotic products, and elimination of inflammatory food. Following the intervention, serum fasting blood sugar and high-sensitivity C-reactive protein levels were significantly decreased in the AID (p=.006 and .002, respectively), G (p=.04 and <.001, respectively), and GPA (p <.001 in both cases, respectively) groups. Further, in the G and GPA groups, there was a significant decrease in body mass index (p=.04 in both cases, respectively), waist circumference (p=.009 and .003, respectively), waist-to-height ratio (p=.02 and .005, respectively), alanine aminotransferase (p=.004 and <.001, respectively), total cholesterol (p=.0002 and .0001, respectively) and low-density lipoprotein-cholesterol (p < .001 and <.001, respectively). Eventually, serum aspartate aminotransferase was decreased (p < .001) and high-density lipoprotein-cholesterol (p=.03) was increased significantly in the GPA group. As a main finding of this study, hepatic steatosis significantly decreased in the G and GPA groups. Ginger supplementation can effectively improve NAFLD in children, and its effectiveness was further increased when combined with an AID.

Analysis of clinical findings and serum micronutrients in pediatric patients with nonalcoholic fatty liver disease

Aim: Nonalcoholic fatty liver disease (NAFLD) is the hepatic finding of systemic lipid and energy metabolism disorder. NAFLD is frequently observed in people with higher body mass index. Serum micronutrient levels play an important role in hepatic metabolism. Material and Method: This study included 60 NAFLD and 66 control patients. . NAFLD and control groups were compared in terms of ultrasonography (USG) and shear wave elastography (SWE) results. The two groups were compared in serum lipid profile, aminotransferase, insulin, glucose, and HOMA-IR. Both groups were then analyzed in terms of serum ferritin, B12, and vitamin D levels.Results: . 35% (n=21) of the patients in the NAFLD group had grade 1, 55% (n=33) had grade 2 and 10% (n=6) had grade 3 adiposity. HOMA-IR and insulin levels were higher in the NAFLD group (p=0.02; p=0.001). While the serum ferritin level of the patients in the NAFLD group was higher than the control group (p=0.001); the B12 level was lower (p=0.006). In terms of vitamin D, there was no difference (p=0.368). Conclusion: It is essential to identify risk factors in children on follow-up due to NAFLD. USG and liver function tests remain the first option in the diagnosis and screening of NAFLD in children. Serum ferritin, B12, and vitamin D levels of children on follow-up due to NAFLD should be analyzed in consideration of liver fattening.