Nonalcoholic Fatty Liver Disease In Adolescents Research Articles

Relationship of the Degree of Sarcopenia with the Severity of Nonalcoholic Fatty Liver Disease and Cardiometabolic Risk in Adolescents.

The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia has been suggested. We investigated sarcopenia's impact on NAFLD severity and its relationship with cardiometabolic risk in adolescents. We conducted a retrospective study on 122 patients aged 13-18 years and diagnosed with both NAFLD and sarcopenia by laboratory tests, abdominal ultrasound (US), and multifrequency bioelectrical impedance analysis. Sarcopenia was stratified into tertiles based on the skeletal muscle-to-fat ratio (MFR), NAFLD severity was established by the US, and cardiometabolic risk was assessed by the triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP). Compared with the other patients, those in the lower MFR tertiles exhibited a greater severity of NAFLD (p < 0.001) and significantly higher TyG index and AIP. The independent effect of MFR was observed to have a negative correlation with the severity of NAFLD (p < 0.001). Based on the aforementioned results, the degree of sarcopenia can be considered as one of the risk factors of severe NAFLD and might be an indicator of cardiometabolic risk in adolescents. Weight training to reach the amount of muscle mass could be included in the treatment strategies to improve or prevent NAFLD in adolescents with sarcopenia.

A significant and persistent rise in the global burden of adolescent NAFLD and NASH estimated by BMI.

Currently, there is a lack of global or even country/regional level data on adolescent non-alcoholic fatty liver disease (NAFLD) prevalence. However, an evidenced dose-dependent relationship exists between body mass index (BMI) and the risk of NAFLD. We aim to estimate the global and regional prevalence of adolescent NAFLD and related non-alcoholic steatohepatitis (NASH) based on BMI. Sigmoidal fitting curves were generated between BMI and the risk of NAFLD/NASH using the data extracted from the NHANES database. With global and regional BMI data from the NCD-RisC database, adolescent NAFLD/NASH prevalence was estimated at the international, regional, and country levels from 1975 to 2016. The prevalence of adolescent NAFLD/NASH from 2017 to 2030 was also forecasted. The mean NAFLD prevalence was 15.31, and 12.68%, while the mean NASH prevalence was 2.50, and 2.47%, in boys, and girls aged 12-18, respectively. For both boys and girls, NAFLD/NASH prevalence increased with increasing BMI, and age. The global prevalence of adolescent NAFLD/NASH has gradually increased in the period from 1975 to 2016 and will maintain a similar trend between 2017 and 2030. High-income Western Countries had higher adolescent NAFLD/NASH whereas South Asia and Sub-Saharan Africa exhibited relatively lower adolescent NAFLD/NASH prevalence. The estimated annual percentage change (EAPC) of NAFLD prevalence in boys ranged from 0.72% (age 18) to 1.16% (age 12) while that in girls ranged from 0.69% (age 18) to 0.92% (age 12). EAPC of NASH prevalence in boys ranged from 1.65% (age 18) to 1.77% (age 12), and in girls from 1.48% (age 18) to 1.68% (age 12). The adolescent NAFLD/NASH prevalence increases year by year, and its burden varies significantly among different countries and regions. BMI is a precise predictor of NAFLD/NASH prevalence.

Prognostic factors in resolution of nonalcoholic fatty liver disease post bariatric surgery in adolescents

BackgroundThe long-term effect of bariatric surgery on adolescent non-alcoholic fatty liver disease is not clear. ObjectivesTo evaluate longitudinal change in serum alanine aminotransferase (ALT) levels and to determine the factors independently associated with this change over 2 years after bariatric surgery in adolescents with severe obesity. SettingAn observational prospective cohort from the Teen-LABS Consortium. MethodsWe examined the relationship of longitudinal change in serum ALT (% change and normalization) to change in body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), high- (HDL) and low-density lipoprotein cholesterol, A1C and fasting glucose, accounting for age, sex, race-ethnicity, blood pressure, and baseline BMI in 219 adolescents during the first 2 years post-surgery. ResultsMean BMI declined from a baseline of 52.6 to 37.2 kg/m2 at 2 years (P < .01). Alanine aminotransferase decreased significantly from baseline (36.5 [95% CI: 31.4, 41.7]) to 6 months (30.5 [95% CI: 25.4, 35.6]), and remained stable at 12 and 24 months, all P < .01 versus baseline. After adjustment, improvement in BMI, fasting glucose, HOMA-IR, triglycerides, TG/HDL ratio, and HDL were independently associated with reduced ALT at 6 months. These remained significantly associated with a decline in ALT after adjusting for BMI change. The %participants with elevated ALT decreased from 71% at baseline to 42% and 36% at 1 and 2 years post-surgery. ConclusionsBariatric surgery resulted in significant and sustained improvement in ALT levels over 2 years. Although associated with weight loss, this decline was also associated with improved metabolic indices, independent of weight loss.

SAT356 Predicting Nonalcoholic Fatty Liver Disease in Adolescent Girls with Polycystic Ovary Syndrome and Obesity

Abstract Disclosure: J.S. Lo: None. F. Bril: None. A. Taylor: None. N. Morelli: None. M.A. Ware: None. Y. Garcia-Reyes: None. M.J. McPhaul: Employee; Self; Quest Diagnostics. M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Amino Corp. Adolescents with obesity and polycystic ovary syndrome (PCOS) have significant insulin resistance and are at high risk of nonalcoholic fatty liver disease (NAFLD). This risk may be related to increased growth hormone and insulin resistance associated with puberty, in addition to excess testosterone. NAFLD is difficult to diagnose in obese individuals. Intact insulin (II), as measured by mass spectrometry, multiplied by alanine aminotransferase (ALT; II*ALT) has emerged as a strong predictor for NAFLD in adults (ROC 0.94 [0.89-0.99]). However, II*ALT has not been used in predict NAFLD in adolescents with PCOS. To assess the utility of II*ALT measurements in predicting NAFLD in the context of pubertal timing in a high-risk population of adolescents with PCOS and obesity. Participants were screened to confirm PCOS status per 2018 international guidelines. Liver fat fraction was measured with MRI Dixon, and fasting laboratory assessments were performed including traditional insulin (TI) and insulin growth factor-1 (IGF-1), measured with ELISA and ALT, AST. NAFLD was defined as a liver fat ≥5.0%. Mass spectrometry was used to measure intact molecules of II and C-peptide. Seventy-seven adolescent girls with PCOS and obesity who were Tanner 5 and at least 1-year post-menarche were enrolled (age 16.3 ± 1.7 years, BMI 34.9 ± 5.0 kg/m2). There was no difference in the prediction of NAFLD between II and TI (AUROC 0.72 [0.59-0.85] vs. 0.66 [0.53-0.79], p=0.39). Of note, the combination of II*ALT (ROC 0.83 [0.72-0.95], sensitivity 77%, specificity 65%) performed better in predicting NAFLD than II alone (ROC 0.72 [0.59-0.85]), ALT alone (ROC 0.81 [0.71-0.91]), and better than TI*ALT (ROC 0.75 [0.63-0.86]) for the entire cohort (p&amp;lt;0.01 for overall comparison). Patients were divided into 2 groups based on age as a surrogate for pubertal duration (Age &amp;lt;15: n=22, age 13.9 ± 0.8, BMI 32.7 ± 4.9 kg/m2, and Age &amp;gt;15: n=55, age 17.3 ± 0.9, BMI 35.8 ± 4.8 kg/m2). II*ALT had a higher ROC to predict NAFLD in the &amp;gt;15 group (ROC 0.90 [0.81-0.98], sensitivity 97%, specificity 60%) compared to the &amp;lt;15 group (ROC 0.71 [0.41-0.99] sensitivity 81%, specificity 83%), although it did not reach statistical significance. There was no effect of race and ethnicity on these relationships. The II*ALT index performs better than II and ALT alone for the detection of NAFLD and outperforms TI*ALT as well. It is a strong predictor for NAFLD in adolescents &amp;gt;15 years old with PCOS and obesity, with results very similar to those published in adults. However, it is not as robust in adolescents younger than 15 years old, perhaps due to the effect of pubertal hormones altering the relationship between liver fat and insulin concentrations. Presentation Date: Saturday, June 17, 2023

262-LB: Fasting Intact Insulin by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) as a Predictor of Nonalcoholic Fatty Liver Disease in Pediatric Patients

Background: Recent research in adults has shown fasting intact insulin levels measured by mass spectrometry can predict nonalcoholic fatty liver disease (NAFLD) in patients without diabetes; however, there is limited research in children. This study aimed to evaluate fasting intact insulin by LC-MS/MS as a predictive biomarker of NAFLD in adolescents. Methods: This retrospective, cross-sectional study was based on data from four previously conducted studies. Existing clinical laboratory values included fasting intact insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-peptide, and the insulin resistance (IR) score. Hepatic fat was assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) or MR spectroscopy (MRS). NAFLD was defined as intrahepatic fat of ≥5%. Results: A total of 73 children were included in the analysis (64% male; 13.9 ± 2.8 years of age; body mass index (BMI) 29.1 ± 8.5 kg/m2; 56% with NAFLD). Intact fasting insulin, C-peptide, AST, ALT, and IR scores were higher in children with NAFLD compared to non-NAFLD children (P&amp;lt;0.05). Fasting intact insulin measurements predicted NAFLD (area under the receiver operating characteristic curve [AUROC] of 0.83 [95%CI, 0.73-0.93]). When combined with ALT (intact insulin (μU/mL) × ALT (× U/L)), the combined biomarker slightly improved the prediction of NAFLD (AUROC 0.89 [0.81-0.96]), with positive and negative predictive values of 79% and 100%, respectively. Based on maximizing Youden's index, the optimal cutoff points to predict NAFLD were 13.0 μU/mL for intact insulin and 380 μU/mL × U/L for intact insulin × ALT. Conclusion: Our findings support that fasting intact insulin alone, or combined with ALT (intact insulin × ALT), show promise as predictive biomarkers for pediatric NAFLD with high positive and negative predictive values. Additional studies are needed to validate these findings in other pediatric populations. Disclosure H. Huneault: None. D. Ayinde: None. Z. He: None. C. C. Cohen: None. M. J. McPhaul: Employee; Quest Diagnostics. M. B. Vos: Consultant; Boehringer Ingelheim International GmbH, BMS, Intercept Pharmaceuticals, Inc., Novo Nordisk, ProSciento, Eli Lilly and Company. Research Support; Quest Diagnostics, TARGET PharmaSolutions, Inc. Funding National Institutes of Health (R01DK125701); Georgia Clinical Translational Science Alliance (UL1TR002378)

Relationship between nonalcoholic fatty liver disease and hyperandrogenemia in adolescents with polycystic ovary syndrome.

Nonalcoholic fatty liver disease (NAFLD) is common in adults with polycystic ovary syndrome (PCOS), and several studies on adults have investigated its influencing factors. However, factors associated with NAFLD in adolescents with PCOS remain unknown. This study aimed to investigate the presence of NAFLD in adolescents with PCOS using the noninvasive methods of vibration-controlled transient elastography (VCTE) and ultrasonography (USG), along with assessing NAFLD-related metabolic and hormonal risk factors. This study included patients aged 12-18 years who were diagnosed with PCOS according to the Rotterdam criteria. The control group included young women with similar age and body mass index (BMI) z scores, who had menstruated regularly for more than 2 years. Patients with PCOS were divided into hyperandrogenemia and nonhyperandrogenemia groups based on serum androgen level. USG was performed on all patients to evaluate the presence of hepatic steatosis. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed using VCTE (Fibroscan). Clinical, laboratory, and radiological data were compared between groups. This study included 124 adolescent girls aged 12-18 years (61 with PCOS, 63 controls). BMI z scores were similar between groups. Waist circumference and total cholesterol, triglyceride, and alanine aminotransferase levels were higher in the PCOS versus the control group. The presence of hepatic steatosis on USG was similar between groups. However, the rate of hepatic steatosis on USG was higher in patients with hyperandrogenic PCOS (P=0.01). LSM and CAP measurements were similar between groups. No increase in prevalence of NAFLD was observed among adolescents with PCOS. However, hyperandrogenemia is a risk factor for NAFLD. Therefore, adolescents with PCOS and elevated androgen level should be screened for NAFLD.

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence

Background and aimsEpigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.Approach and resultsWe performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10–3).ConclusionsWe identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.Graphical abstract

Exposure to volatile organic compounds and polycyclic aromatic hydrocarbons is associated with the risk of non-alcoholic fatty liver disease in Korean adolescents: Korea National Environmental Health Survey (KoNEHS) 2015–2017

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent liver diseases among adolescents. Several animal studies have suggested that volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) increase NAFLD risk. However, few epidemiological studies have confirmed the association between VOCs, PAHs and NAFLD in the general adolescent population. Therefore, we analyzed 798 adolescents from the Korean National Environmental Health Survey (KoNEHS), 2015–2017, to examine the associations of urinary metabolites of VOCs and PAHs with serum alanine aminotransferase (ALT) activity and NAFLD prevalence. We performed linear regression, logistic regression, and Bayesian kernel machine regression (BKMR) to evaluate the association of urinary VOCs and PAHs metabolites with ALT levels and NAFLD prevalence. After adjusting for all covariates, urinary benzylmercapturic acid and 2-hydroxyfluorene levels were found to increase ALT activity and NAFLD prevalence. Additionally, the BKMR analyses showed a significantly positive overall effect on ALT activity and NAFLD prevalence with urinary concentrations of VOCs and PAHs metabolites, with 2-hydroxyfluorene as the biggest contributor. Our study suggests that exposure to low-level VOCs and PAHs may have a detrimental effect on NAFLD risk in adolescents. Given the increasing prevalence of NAFLD in adolescents, future cohort studies are confirmed to comprehend the effect of these chemicals on NAFLD risk.

Nonalcoholic fatty liver disease in adolescents with phenylketonuria

ObjectiveThis study aimed to investigate non-alcoholic fatty liver disease (NAFLD) occurrence and factors associated with the disease in phenylketonuria (PKU) patients undergoing exclusive dietary treatment. MethodThis cross-sectional study included 101 adolescents 10 to < 20 years of age with PKU, who were undergoing exclusive dietary treatment and monitored since early diagnosis at a single reference service. Anthropometric and biochemical assessments were performed and food intake was documented, and an ultrasound diagnosis of NAFLD was established. Data were evaluated using the Student's t-test for continuous variables, the chi-square for categorical variables, and logistic regression using the Wald chi-squared test; differences with p < 0.05 were considered to be statistically significant. ResultsNAFLD was detected in 26 (25.7%) teenagers. There was no difference in prevalence between the sexes or nutritional status. The final logistic regression model revealed low sensitivity (26.1%) and high specificity (94.7%). The specificity suggested a lower likelihood of NAFLD in older adolescents, in the presence of normal or high levels of alkaline phosphatase, lower carbohydrate intake, and adequate protein and lipid intake. ConclusionsThe prevalence of NAFLD in adolescents with PKU was higher than that found in healthy Brazilian adolescents and similar to that found in obese Brazilian children, suggesting a higher risk for NAFLD in patients with PKU treated exclusively by dietary modification.

Urinary metabolites of volatile organic compounds and polycyclic aromatic hydrocarbons increases the risk of nonalcoholic fatty liver disease in Korean adolescents: A Korean National Environmental Health Survey (KoNEHS) 2015-2017 analysis

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in adolescents and is an urgent public health issue. Several animal studies have suggested that volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) led to NAFLD. However, few epidemiological studies have confirmed the associations of VOCs and PAHs with NAFLD in the general adolescent population. Therefore, we analyzed 798 adolescents from the Korean National Environmental Health Survey (KoNEHS) 2015-2017 to examine the associations of urinary metabolites for VOCs and PAHs with serum alanine aminotransferase (ALT) activity and NAFLD prevalence. We employed linear, logistic regression, and Bayesian kernel machine regression (BKMR) to evaluate the association of urinary VOCs and PAHs metabolites with ALT activity and NAFLD. After adjusting for all covariates, urinary benzylmercapturic acid level and 2-hydroxyfluorene level increased serum ALT activity and NAFLD prevalence. Additionally, the BKMR analyses showed a significantly positive overall effect on ALT activity and NAFLD prevalence with urinary concentrations of VOCs and PAHs metabolites, and 2-hydroxyfluorene contributed the most. Our study suggests that exposure to low-level VOCs and PAHs may have a detrimental effect on NAFLD risk in adolescents. Given the increasing prevalence of NAFLD in adolescents, future cohort studies are warranted to understand these chemicals’ impact on NAFLD risk. Keywords: volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), adolescents, Non-alcoholic fatty liver disease, Korean National Environmental Health Survey (KoNEHS)

Nonalcoholic Fatty Liver Disease in Young Children with Obesity.

Background: To evaluate the prevalence of suspected nonalcoholic fatty liver disease (NAFLD) in young children with obesity and determine associated risk factors. Methods: Retrospective single-center study of children with obesity, ages 2-6 years. Suspected NAFLD was defined as an alanine aminotransferase (ALT) >30 U/L. Multivariable analyses were performed to determine predictors of elevated ALT. Results: Among 237 children 2-6 years old, 35% had elevated ALT. Multivariable analysis showed that higher BMI z score [odds ratio (OR): 1.5 confidence interval (95% CI: 1.04-1.92)] and higher gamma-glutamyl transferase (GGT) [OR: 21.3 (95% CI: 3.7-121.1)] predicted elevated ALT. Of those with ≥2 ALT levels, 38% (n = 33/86) had a persistently elevated ALT (median ALT >30 U/L). Only 7% of patients with ALT >30 U/L underwent further testing to evaluate for alternative causes of liver disease. Conclusion: Suspected NAFLD is common in young children with obesity and predicted by obesity severity and GGT. Other cardiometabolic markers were equivalent between those with normal vs. elevated ALT, suggesting NAFLD onset may precede development of comorbidities. Earlier screening will enable prompt diagnosis and intervention, which may prevent or delay the onset of cardiometabolic diseases commonly associated with NAFLD in adolescence and adulthood.

1168-P: Serum MicroRNA-122 and -192 Are Increased in Adolescents with NAFLD: Potential Role as Biomarkers

The best available blood biomarker for nonalcoholic fatty liver disease (NAFLD) is alanine aminotransferase (ALT), though it does not reliably distinguish NAFLD severity. Alternate biomarkers have been tested in adults, but fewer in children. We tested serum microRNA-122 (miR-122) as a biomarker for NAFLD in adolescents since it inhibts hepatic lipogenesis in animals and is exported from liver to blood with disease progression. The only prior study of miR-122 in children produced mixed results. We also measured miR-192, -130b, and -155 as they have roles in hepatic lipogenesis. Participants were boys and girls, 12-20 y, with biopsy-confirmed NAFLD (n=23), and peers without NAFLD who were either obese (Ob, n=22), or normal weight (NW, n=24). RNA was extracted from serum from all participants and from liver biopsies from the NAFLD group. Serum miR-122 and -192 were 12- and 10-fold higher (p&amp;lt; 0.01), respectively, in NAFLD patients compared to both Ob and NW controls. Within the NAFLD group, serum abundances of miR-122 and -192 were inversely correlated with their liver values (r = -0.51, p = 0.002 and r = -0.40, p = 0.067, respectively), and positively correlated with histological scores for steatosis (r = 0.39 and 0.28, respectively) and fibrosis (r = 0.56 and 0.54, respectively). mIR-122 and -192 content were also positively correlated with ALT (r = 0.78 for both) and with each other in both serum (r = 0.92) and liver (r = 0.74), suggesting similar regulation. Areas under the receiver operating curve for distinguishing NAFLD was 0.95 for miR-122 and -192. Serum miR-130b, which regulates PGC-1 alpha, was 2.6-fold higher in serum from NAFLD patients versus both control groups, while serum miR-155, which regulates lipogenesis and inflammation, did not differ in NAFLD. Serum miR-130b and miR-155 values were not correlated with their corresponding values in liver biopsies. These results support the potential use of miR-122 and -192 as biomarkers for the presence and severity of NAFLD in adolescents. Disclosure K. R. Short: None. S. Palle: None. D. S. Amaya hellman: None. S. Jiang: None. J. B. Tryggestad: None. E. Fematt garcia: None. Funding Oklahoma Shared Clinical &amp; Translational Resource

Non-alcoholic Fatty Liver Disease in Asian Indian Adolescents and Young Adults

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the youth. The aim of the study was to conduct a metabolic risk factor profiling of NAFLD in adolescents and young adults in Chennai city in south India. Materials and Methods: The study participants included adolescents (n = 188) and young adults (n = 201). Ultrasonographic examination of the abdomen was done using a high-resolution B mode ultrasonography system. Based on the intensity of echogenicity, various grades of fatty liver were classified. Anthropometry, fasting plasma glucose, serum insulin, total cholesterol, triglycerides, and HDL and LDL cholesterol were estimated. χ2 analysis was performed to compare frequencies and t-tests on continuous or measurable data. Odds ratio (OR) was used as an indicator for strength of association. Results: From the total of 389 study participants, 70 had NAFLD which includes 48 with grade I, 21 with grade II, and one participant with grade III NAFLD. About 80% of the participants with NAFLD were adults (≥20 years) and more males were affected (70%) than females (30%). Generalized obesity was present in 90% of the participants with NAFLD. After adjusting for age and gender, obesity [OR: 5.88; 95% confidence interval (CI): 2.53–13.69; P-value: &lt;0.001] and hyperglycemia [OR: 4.20; 95% CI: 1.75–10.08; P-value: &lt;0.001] were significantly associated with NAFLD. Conclusion: With the higher prevalence rates of NAFLD noted in the study participants, prevention modalities should be adopted in the community by reducing obesity, healthy diet, and increased physical activity.

Adolescent Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Young Adulthood.

The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear. To assess type 2 diabetes risk among adolescents with NAFLD. A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016. A total of 1 025 796 normoglycemic adolescents were included. Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry. Type 2 diabetes incidence. During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74]). Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years.

Inborn errors of metabolism in the differential diagnosis of fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease across all age groups. Obesity, diabetes, and metabolic syndrome, are the primary causes that are closely linked with the development of NAFLD. However, in young children, rare inborn errors of metabolism are predominant secondary causes of NAFLD. Furthermore, inborn errors of metabolism causing hepatosteatosis are often misdiagnosed as NAFLD in adolescents and adults. Many inborn errors of metabolism are treatable disorders and therefore require special consideration. This review aims to summarize the basic characteristics and diagnostic clues of inborn errors of metabolism associated with fatty liver disease. A suggested clinical and laboratory diagnostic approach is also discussed.

Effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta-analysis of paediatric and adolescent individuals.

The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic fatty liver disease (NAFLD) remains inconclusive. We aimed to estimate the effect of this polymorphism not only on early-onset NAFLD risk and severity but also on metabolic syndromes susceptibility. A systematic literature search was performed to identify relevant datasets. The odds ratio of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals were calculated to assess the strength of the associations. Twenty-seven studies comprising 10 070 subjects were eligible. The summary effect showed that this polymorphism increased susceptibility to NAFLD development. Furthermore, it also indicated that nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers among paediatric and adolescent NAFLD patients. Moreover, the meta-analysis suggested that the variant was significantly associated with elevated liver damage indexes, including serum alanine transaminase, aspartate transaminase, gamma-glutamyltransferase concentrations, and liver fat content. However, the summary estimates for insulin resistance, lipid metabolism, and adiposity showed no significant associations. The PNPLA3 I148M polymorphism is associated with elevated early-onset NAFLD risk, severity, and liver damage but not with related metabolic syndromes.

Early Obesity: Risk Factor for Fatty Liver Disease.

The aim of the study was to identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002 to 2003, with yearly anthropometric data collected over a 10-year period. The presence of intrahepatic fat in the livers of subjects 14 to 16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. 9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (≥7 kPa) had greater weight, BMI z-score, waist and hip circumference, and altered liver enzymes (P < 0.05). The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.

Metabolic profiling of adolescent non-alcoholic fatty liver disease.

Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.

Metabolic profiling of adolescent non-alcoholic fatty liver disease

Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.

Metabolic profiling of adolescent non-alcoholic fatty liver disease.

Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.