Search

Purpose The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity. Methods Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD. Results Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (pG had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype. Conclusion In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.

Acute otitis media (AOM) is the commonest disease of childhood. High incidence of AOM might be due to immature Eustachian Tube and immaturity of immune system. Exclusive breast feeding is protective against acute otitis media, however, improper breastfeeding position can increase AOM occurrence in infants. This study aims to assess the association of improper breastfeeding position with occurrence of Acute otitis media in infants and to assess association of Maternal educational levels with feeding positions. 220 breastfed infants satisfying inclusion criteria with diagnosed AOM were enrolled. Study was conducted over a period of 6 months from August 2019 to January 2020. Demographic details and Detailed history regarding feeding positions and maternal educational levels were obtained through a Self-structured proforma from parents. Data analysis was done through descriptive statistics and chi square test and p value less than 0.5 was set significant. Out of 220 infants, 123(55.90%) were male and 97(44.10%) were females. AOM was more common in male infants than female infants, however it was not statistically significant(p=0.169). The mean age for enrolled infants(1-12months) was 6.90(±3.413). Statistically significant association between increase incidence of AOM and breastfeeding position was found(p=0.032). We also found a statistically significant association between maternal educational levels and breastfeeding position (p= 0.000). In this study, we have noted that Breastfeeding in supine position is associated significantly with increase in incidence of AOM. Feeding positions are statistically associated with Maternal Educational levels.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic and affects approximately 10% of children in the US. The presence of hepatic fibrosis may be the most important factor in determining the prognosis of NAFLD. Noninvasive methods to identify the presence of fibrosis in children with NAFLD are greatly needed. Hepatocyte apoptosis activates hepatic stellate cells and plays a central role in fibrosis progression in NAFLD. The aim of the present study was to evaluate the use of plasma cytokeratin-18 (CK18) fragment levels, a marker of hepatocyte apoptosis, as a noninvasive biomarker in detecting liver fibrosis in pediatric NAFLD.Consecutive children with biopsy-proven NAFLD were included and blood samples and anthropometric measurements were collected at the time of the biopsy. NAFLD activity score was calculated (0-8) and fibrosis stage was scored (0-4). We measured plasma CK18 levels using the M30-Apoptosense enzyme-linked immunosorbent assay kit.A total of 201 subjects were enrolled in the study. The mean age was 10.7 ± 2.5 years, and 37 % were boys. Sixty-eight percent of the patients had any fibrosis, with 56% having F1, 6% having F2, and 6 % having F3. CK18 levels were found to be significantly higher in subjects with any fibrosis compared with those without fibrosis (304.6 ± 124.8 vs 210.4 ± 70.9, P 0.001). CK18 level revealed good accuracy for prediction of any fibrosis (F1-F3) with AUROC of 0.75. Multivariate logistic regression was performed to assess whether CK18 in combination with another clinical factor could improve accuracy of prediction of fibrosis. Together, CK18 with waist circumference percentile generated an area under the receiver operating characteristics curve of 0.842 for prediction of any fibrosis.CK18 is a promising noninvasive biomarker for fibrosis in NAFLD in children. A fibrosis prediction model that includes CK18 and waist circumference percentile should be validated in other populations.

Background: Body weight homeostasis and the progression of obesity to comorbidities such as nonalcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) involve the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. Data on the role of a gut-adipose axis in children with obesity-related comorbidities are sparse. We determined novel signals in the gut-adipose axis such as pro-uroguanylin (PUG) produced in the gut and spexin, predominantly produced in white adipose tissue along with traditional appetite/satiety hormones in insulin-resistant children with (NASH) and simple obesity. Method: A total of 29 children (age: 8-17 years) in three groups, normal weight (NW; n=11; BMI95th%) and biopsy-proven NASH (n=9; NAS-score>2) were studied. Spexin, PUG, leptin, total (T)- and high molecular weight (HMW)-adiponectin and insulin were measured. Results: Spexin, PUG and both T and HMW adiponectins were lower in children with NASH compared to both children with simple obesity and their NW counterparts, while leptin and insulin were higher (p Conclusions: Lower concentrations of novel signals such as PUG and spexin in the current study suggest that perturbations in the gut-brain axis occur at an early age in the clinical course of obesity and NASH. The potential role of these novel gut-adipose axis signals, by themselves or in unison with other factors, in diagnosing and/or monitoring the development and/or progression of obesity-related comorbidities such as NASH, T2DM and CVD as well as the potential development of more directed therapies appears to be promising and warrants further studies. Disclosure M.D. Di Guglielmo: None. S. Mansoor: None. V. Uppal: None. K.N. Furuya: None. S. Kumar: None. P. Balagopal: None.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and can progress to liver cirrhosis during childhood. Patients with more advanced fibrosis on biopsy tend to have more liver complications. Noninvasive hepatic fibrosis scores have been developed for adult patients with NAFLD; however, these scores have not been validated in children. The aim of our study was to evaluate some of these scores in assessing the presence of fibrosis in children with biopsy-proven NAFLD. Methods Our study consisted of 92 biopsy-proven NAFLD children from five major US centers. Fibrosis was determined by an experienced pathologist (F0‐4). Clinically significant fibrosis was defined as fibrosis stage C2, and advanced fibrosis was defined as F3‐4. The following fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 index. ROC was performed to assess the performance of different scores for prediction of presence of any, significant, or advanced fibrosis. A p value \0.05 was considered statistically significant. Results Mean age was 13.3 ± 3 years, and 33 % were females. Eleven (12 %) subjects had no fibrosis, 35 (38 %) had fibrosis score of 1, 26 (28 %) had fibrosis score of 2, and 20 (22 %) had a score of 3. APRI had a fair diagnostic accuracy for the presence of any fibrosis (AUC of 0.80) and poor diagnostic accuracy for significant or advanced fibrosis. AST/ALT, NFS, and FIB-4 index all either had poor diagnostic accuracy or failed to diagnose the presence of any, significant, or advanced fibrosis. Conclusion Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing significant fibrosis in children with NAFLD. Our results highlight the urgent need to develop a reliable pediatric fibrosis score.

Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

Background Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis. Methods Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0-4). Advanced fibrosis was defined as fibrosis stage ≥ 3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis. Results Our cohort consisted of 242 children with a mean age of 12.4 ± 3.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0-2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) - (1.1*log(platelets) - (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p = 100 × exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index. Conclusion Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.

Background: Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis. Methods: Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0–4). Advanced fibrosis was defined as fibrosis stage $3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis. Results: Our cohort consisted of 242 children with a mean age of 12.463.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0–2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z=1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) – (1.1*log(platelets) – (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p=1006exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index. Conclusion: Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.