Liver Disease In Children Research Articles

Relation between Body Composition Trajectories from Childhood to Adolescence and Nonalcoholic Fatty Liver Disease Risk.

NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the 'Chilean Growth and Obesity Cohort Study', comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years (p = 0.03), all skin folds from age 4 years (p < 0.01), and DXA body fat measurements from age 12 years (p = 0.01). The fat-free mass index was higher in females (p = 0.006) but not in males (p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48-3.25, 95% CI) and 6.94 (4.79-10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.

Gut microbiota in autoimmune and non-autoimmune liver diseases in children

Relevance. The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children - Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose of the study. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Scope and methods of research. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3±4.7 years) was carried out with the identification of the V3-V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Research results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ faeces. The analysis of the conducted studies showed that no dominant taxa were found in the faecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Comparative assessment of intestinal microbiota in autoimmune and non-autoimmune liver diseases in children

The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children — Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the isolation of the 16S rRNA gene region. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. The analysis of the conducted studies showed that no dominant taxa were found in the fecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Diagnosis, Management, and Prognosis of Cystic Fibrosis-Related Liver Disease in Children.

Cystic fibrosis (CF) is a multifaceted disorder predominantly investigated for its pulmonary manifestations, yet patients with CF also exhibit a spectrum of extrapulmonary manifestations, notably those involving the hepatobiliary system. The latter constitutes the third leading cause of morbidity and mortality in individuals with CF. Cystic fibrosis-related liver disease (CFLD), with an escalating prevalence, manifests diverse clinical presentations ranging from hepatomegaly to cirrhosis and hepatopulmonary syndrome. Consequently, early detection and appropriate management are imperative for sustaining the health and influencing the quality of life of CF patients afflicted with CFLD. This review aims to consolidate existing knowledge by providing a comprehensive overview of hepatobiliary manifestations associated with CF. It delineates the clinical hepatobiliary manifestations, diagnostic methodologies, incorporating minimally invasive markers, and therapeutic approaches, encompassing the impact of novel CFTR modulators on CFLD. Given the exigency of early diagnosis and the intricate management of CFLD, a multidisciplinary team approach is essential to optimize care and enhance the quality of life for this subset of patients. In conclusion, recognizing CF as more than solely a pulmonary ailment, the authors underscore the imperative for further clinical investigations to establish a more robust evidence base for CFLD management within the continuum of this chronic disease.

Validation of a screening panel for pediatric metabolic dysfunction-associated steatotic liver disease using metabolomics.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD, is the most common liver disease in children. Liver biopsy remains the gold standard for diagnosis, although more efficient screening methods are needed. We previously developed a novel NAFLD screening panel in youth using machine learning applied to high-resolution metabolomics and clinical phenotype data. Our objective was to validate this panel in a separate cohort, which consisted of a combined cross-sectional sample of 161 children with stored frozen samples (75% male, 12.8±2.6 years of age, body mass index 31.0±7.0kg/m2, 81% with MASLD, 58% Hispanic race/ethnicity). Clinical data were collected from all children, and high-resolution metabolomics was performed using their fasting serum samples. MASLD was assessed by MRI-proton density fat fraction or liver biopsy and cardiometabolic factors. Our previously developed panel included waist circumference, triglycerides, whole-body insulin sensitivity index, 3 amino acids, 2 phospholipids, dihydrothymine, and 2 unknowns. To improve feasibility, a simplified version without the unknowns was utilized in the present study. Since the panel was modified, the data were split into training (67%) and test (33%) sets to assess the validity of the panel. Our present highest-performing modified model, with 4 clinical variables and 8 metabolomics features, achieved an AUROC of 0.92, 95% sensitivity, and 80% specificity for detecting MASLD in the test set. Therefore, this panel has promising potential for use as a screening tool for MASLD in youth.

Respiratory problems associated with liver disease in children.

Respiratory manifestations of chronic liver disease have a profound impact on patient clinical outcomes. Certain conditions within paediatric liver disease have an associated respiratory pathology. This overlap between liver and respiratory manifestations can result in complex challenges when managing patients and requires clinicians to be able to recognise when referral to specialists is required. While liver transplantation is at the centre of treatment, it opens up further potential for respiratory complications. It is established that these complications place patients at risk of longer stays in hospital and reduced survival. Additionally, late post-transplant complications can occur, including post-transplant lymphoproliferative disease and immunosuppression-induced interstitial lung disease. Although rare, it is important for clinicians to recognise these conditions to allow for prompt management. Finally, as liver disease progresses in children, respiratory complications can occur. Hepatopulmonary syndrome can occur in the context of portal hypertension, resulting in increased mortality and poorer quality of life for patients. Another consequence is portopulmonary hypertension, which can be associated with poor survival. Failure to recognise these complications in children may result in poorer outcomes and therefore it is vital that clinicians can establish when referral to a paediatric respiratory medicine specialist is required.

PARVB and HSD17B13 variants are associated with nonalcoholic fatty liver disease in children.

The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of TM6SF2, PNPLA3, and SAMM50 in Korean children. A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated. Transient elastography was performed in 69 some patients with nonalcoholic fatty liver disease. TaqMan allelic discrimination assays were used for genotyping. The genetic risk scores were calculated using significant variants, namely, HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2, to evaluate the additive effect. Risk allele carriers of the PARVB variant showed significantly higher levels of aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, pediatric nonalcoholic fatty liver disease fibrosis score, and aspartate aminotransferase/platelet ratio index. Individuals with a homozygous variant of HSD17B13 showed significantly lower levels of aminotransferase, gamma-glutamyl transferase, liver stiffness measurement, and aspartate aminotransferase/platelet ratio index than those with other genotypes. These parameters did not significantly differ among other variants of LYPLAL1, GCKR, TRIB1, APOC3, and MBOAT7. The genetic risk scores was identified as an independent risk factor for nonalcoholic fatty liver disease and had a positive association with severity. HSD17B13 has protective effects on the severity of pediatric nonalcoholic fatty liver disease. Variants of HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2 had an additive effect on nonalcoholic fatty liver disease.

Breaking boundaries: Unraveling metabolic dysfunction-associated steatotic liver disease in children of India and Canada

Background: Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease in children. Its prevalence is rising globally, yet it is uncertain if its onset and severity vary between countries. We aimed to compare pediatric NAFLD in two Canadian and Indian tertiary care centers. Methods: This study was conducted as a retrospective cohort study and patient related details were retrieved from the electronic records and reviewed. Results: The study analyzed a total of 184 children with NAFLD/MASLD (94 from the Indian site and 89 from the Canadian site) with concordance between NAFLD and MASLD definitions. The Indian children had a higher proportion of symptomatic presentations and family history of metabolic disorders ( p = 0.0001) while the Canadian children had higher median weight, BMI, blood pressure, and waist circumference ( p &lt; 0.05). Indian children had higher hepatic transaminases and low density lipoprotein levels, while the Canadian site had higher serum insulin, blood glucose, homeostasis model assessment of insulin resistance, high density lipoprotein cholesterol levels, liver stiffness, and controlled attenuation parameter values ( p &lt; 0.05). Majority (78%) of the Canadian children who underwent liver biopsy had significant fibrosis (&gt;stage 2). In the overall cohort, waist circumference could be identified as an independent risk factor, irrespective of country of origin, predicting hepatic fibrosis. Conclusions: The study found significant differences between cohorts. Canadian children showed higher obesity grades and greater hepatic steatosis and fibrosis severity. To comprehend the underlying causes, future studies are imperative.

Glucagon-like Peptide-1 Receptor Agonists-A Potential New Medication for Pediatric Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the US and, if untreated, may progress to end-stage liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown improvement in MASLD markers in adults with type 2 diabetes mellitus (T2DM). Currently, there is a lack of medications available for the treatment of pediatric MASLD. We aimed to provide preliminary data on the effects of GLP-1 RAs on markers of MASLD in a retrospective study, in an effort to bridge this gap in the pharmacotherapies available. Nine patients from a T2DM clinic who met the following inclusion criteria were included in this study: patients diagnosed with pre-diabetes or T2DM, prescribed a GLP-1 RA in the prior 12 months, and having alanine aminotransferase (ALT) elevated to twice the upper limit of the normal range, indicating evidence of MASLD. The average change between baseline and the first measurement after starting a GLP-1 RA was calculated for ALT, hemoglobin A1c, and BMI. ALT decreased by an average of 98 points. A1c decreased by an average of 2.2 points. BMI decreased by an average of 2.4 points. There was greater reduction in ALT and A1c compared to BMI, suggesting that improvement in MASLD may be independent of weight loss. This is a preliminary study that shows potential, and prospective studies are needed to evaluate the effects of GLP-1 RAs in the management of pediatric MASLD.

Adrenarche-accompanied rise of adrenal sex steroid precursors prevents NAFLD in Young Female rats by converting into active androgens and inactivating hepatic Srebf1 signaling

BackgroundNon-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease in children and adolescents, but its etiology remains largely unknown. Adrenarche is a critical phase for hormonal changes, and any disturbance during this period has been linked to metabolic disorders, including obesity and dyslipidemia. However, whether there is a causal linkage between adrenarche disturbance and the increasing prevalence of NAFLD in children remains unclear.ResultsUsing the young female rat as a model, we found that the liver undergoes a transient slowdown period of growth along with the rise of adrenal-derived sex steroid precursors during adrenarche. Specifically blocking androgen actions across adrenarche phase using androgen receptor antagonist flutamide largely increased liver weight by 47.97% and caused marked fat deposition in liver, thus leading to severe NAFLD in young female rats. Conversely, further administrating nonaromatic dihydrotestosterone (DHT) into young female rats across adrenarche phase could effectively reduce liver fat deposition. But, administration of the aromatase inhibitor, formestane across adrenarche had minimal effects on hepatic de novo fatty acid synthesis and liver fat deposition, suggesting adrenal-derived sex steroid precursors exert their anti-NAFLD effects in young females by converting into active androgens rather than into active estrogens. Mechanistically, transcriptomic profiling and integrated data analysis revealed that active androgens converted from the adrenal sex steroid precursors prevent NAFLD in young females primarily by inactivating hepatic sterol regulatory element-binding transcription factor 1 (Srebf1) signaling.ConclusionsWe firstly evidenced that adrenarche-accompanied rise of sex steroid precursors plays a predominant role in preventing the incidence of NAFLD in young females by converting into active androgens and inactivating hepatic Srebf1 signaling. Our novel finding provides new insights into the etiology of NAFLD and is crucial in developing effective prevention and management strategies for NAFLD in children.

Nutrition in Pediatric Liver Disease.

In liver disease, there is derangement of appetite, digestion, absorption, assimilation, storage and metabolism of both macro and micronutrients. These derangements have an impact on mortality and morbidity associated with liver diseases. In infants, breast feeds should not be stopped unless there are compelling reasons such as underlying metabolic problem. Parenteral nutrition should be considered only if, oral or nasogastric feeding is not possible. The effect of malnutrition on liver disease and impact of liver failure on nutrition is vicious and nutritional intervention has to be done at the earliest to break that vicious cycle. This chapter gives an overview of nutritional management in acute and chronic liver diseases in children and also its impact on specific clinical scenarios including liver transplantation.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Pediatricians' practices and knowledge of metabolic dysfunction-associated steatotic liver disease: An international survey.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in children. It is associated with significant intra- and extrahepatic comorbidity. Current guidelines lack consensus, potentially resulting in variation in screening, diagnosis and treatment practices, which may lead to underdiagnosing and/or insufficient treatment. The increasing prevalence of MASLD and associated long-term health risks demand adequate clinical management and consensus in guidelines. This study aims to evaluate the daily practices of pediatricians in screening, diagnosis and treatment of MASLD in children. An online survey with 41 questions (single/multiple response options) was sent to pediatricians (with/without subspecialty) in Europe and Israel, via members of the ESPGHAN Fatty Liver Special Interest Group, between June and November 2022. The 454 pediatricians were included in this study. 51% of pediatricians indicated using any guideline for diagnosis and treatment of MASLD, with 68% reporting to follow recommendations only partially. 63% is of the opinion that guidelines need revision. The majority of pediatricians screen for MASLD with liver function tests and/or abdominal ultrasound. A large variety of treatment options is utilized, including lifestyle management, supplements and probiotics, with a notable 34% of pediatricians prescribing pharmacotherapy. When asked how often pediatricians request a liver biopsy in children with MASLD, 17% indicates they request a liver biopsy in more than 10% of cases. There is limited awareness and considerable variation in screening, diagnosis and treatment practices among European pediatricians, and a clear demand for new, uniform guidelines for MASLD in children.

Biomarkers of fibrosis and portal hypertension in Fontan-associated liver disease in children and adults

BackgroundFontan-associated liver disease (FALD) refers to structural and functional changes of the liver caused by the physiology of the Fontan palliation. Currently, liver biopsy is the gold standard to assess liver fibrosis of FALD. AimInvestigate biomarkers correlating with severity of liver biopsy fibrosis in FALD. MethodsA retrospective study of post-Fontan patients ≥ 10 years of age who underwent liver biopsy was conducted. Advanced liver disease (ALD) was defined as bridging fibrosis and/or cirrhosis on liver biopsy. AST-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) from FibroScan were used as non-invasive fibrosis scores. ResultsSixty-six patients (26/47; 55.3% adults and 13/19 children; 68.4%) had ALD on biopsy. ALD was associated with lower platelet count (151 vs. 198 K/uL, p = 0.003), higher APRI (0.64 vs. 0.32, p = 0.01), higher FIB-4 (0.64 vs. 0.32, p = 0.02). Liver fibrosis score correlated with APRI (0.34, p = 0.02) and FIB-4 (0.47, p = 0.001) in adults. LSM had a high sensitivity at 81.3% with 45.5% specificity at a cut-off 18.5 kPa. ConclusionsAPRI and FIB-4 had modest discrimination to identify adults with advanced liver disease, but not children, indicating that these values may be followed as a marker of FALD progression in older patients.

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.

Serum glutathione peroxidase is associated with nonalcoholic fatty liver disease in children and adolescents.

oxidative stress is an important factor in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the serum levels of malondialdehyde (MDA), glutathione peroxidase (GPx) and antioxidant micronutrients in children and adolescents with and without NAFLD. a cross-sectional study with patients between 8-18 years old, of both sexes. Diagnosis of NAFLD: presence of steatosis on ultrasound and absence of history of ethanol consumption and other liver diseases. Anthropometric measures, MDA, GPx, Interleukin-6, serum levels of vitamins A, C and E, selenium, zinc, and copper were evaluated. eighty-nine children with mean age of 12 (3) years, 57.3 % female and 24 % with NAFLD were evaluated. Those with NAFLD had more frequent abdominal obesity (high waist-height ratio: 81.0 % x 48.5 %; p = 0.009). After logistic regression NAFLD was associated with high body mass index/age (p-adjusted = 0.021) and with reduced serum GPx (p-adjusted = 0.034). There was a positive correlation between MDA and copper (r = 0.288; p = 0.006), IL-6 (r = 0.357; p = 0.003) and a negative one with vitamin A (r = -0.270; p = 0.011). oxidative stress is present in children with NAFLD and non-invasive markers such as GPx and BMI can be used in clinical practice and help in the early screening of NAFLD.

Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children. Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls. GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01). GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.

Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.

Caroli’s Disease vs Caroli Syndrome: Clinical and Radiological Spectrum, with disease Outcome at a Teaching Hospital in Lahore

Background: Caroli disease and Caroli syndrome are part of the clinical spectrum of ductal plate (DP) malformations, also referred to, as the fibrocystic liver diseases. This article aimed to study both these conditions, in terms of clinical features and disease outcome at a teaching hospital. Objective: To describe the clinical spectrum, laboratory and imaging findings, management course and outcome of fibrocystic liver diseases in children, at the University of Child Health Sciences, Lahore, Pakistan. Study Design: Cross-sectional Study. Settings: Department of Pediatric Gastroenterology &amp; Hepatology, University of Child Health Sciences, Lahore Pakistan. Duration: January 2014 to July 2017. Methods: The study included patients with Caroli disease and Caroli Syndrome, confirmed on the basis of characteristic findings on magnetic resonance cholangiopancreatography. SPSS v.20 was used for statistical analysis. Results: The mean age of 15 patients included in the study was 6.54 ± 4.18 years. Among them, 7/15 (46.7%) had Caroli’s disease (CD), whereas 8/15 (53.3%) had Caroli’s syndrome (CS). Male to female ratio was 4:1. CS pre-dominantly affected male children (8:0), while CD affected both genders almost equally (4:3). CD commonly presented with recurrent cholangitis (6/7, 85%), while CS as portal hypertension (7/8, 87.5%). Renal involvement was found in 5/15(33.33%) patients; mostly in CS (4/5,80%) and one (6.66%) patient progressed to end stage renal disease. One patient of CD underwent lobectomy and one died of end stage liver disease. Two patients of CS were treated with shunt surgery with partial splenectomy. Six patients are doing well after endoscopic variceal band ligation and propranolol prophylaxis. Conclusion: Caroli disease and Caroli syndrome are two sides of the same coin; it is important to differentiate the two disorders, especially from management point of view. CS is more common in our set up, leading to portal hypertension, which can be treated with sclerotherapy, endoscopic band ligation or shunt surgery. CD leads to cholangitis, which is managed with antibiotics.