Liver Disease In Children Research Articles

Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents

Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2–8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.

Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.

Cholestatic liver disease is a leading referral to pediatric liver transplant centers. Inherited disorders are the second most frequent cause of cholestasis in the first month of life. We retrospectively characterized the genotype and phenotype of 166 participants with intrahepatic cholestasis, and re-analyzed phenotype and whole-exome sequencing (WES) data from patients with previously undetermined genetic etiology for newly published genes and novel candidates. Functional validations of selected variants were conducted in cultured cells. Overall, we identified disease-causing variants in 31% (52/166) of our study participants. Of the 52 individuals, 18 (35%) had metabolic liver diseases, 9 (17%) had syndromic cholestasis, 9 (17%) had progressive familial intrahepatic cholestasis, 3 (6%) had bile acid synthesis defects, 3(6%) had infantile liver failure and 10 (19%) had a phenocopy of intrahepatic cholestasis. By reverse phenotyping, we identified a de novo variant c.1883G > A in FAM111B of a case with high glutamyl transpeptidase (GGT) cholestasis. By re-analyzing WES data, two patients were newly solved, who had compound heterozygous variants in recently published genes KIF12 and USP53, respectively. Our additional search for novel candidates in unsolved WES families revealed four potential novel candidate genes (NCOA6, CCDC88B, USP24 and ATP11C), among which the patients with variants in NCOA6 and ATP11C recapitulate the cholestasis phenotype in mice models. In a single-center pediatric cohort, we identified monogenic variants in 22 known human intrahepatic cholestasis or phenocopy genes, explaining up to 31% of the intrahepatic cholestasis patients. Our findings suggest that re-evaluating existing WES data from well-phenotyped patients on a regular basis can increase the diagnostic yield for cholestatic liver disease in children.

Ascites and Chronic Liver Disease in Children.

Development of ascites in children with chronic liver disease is the most common form of decompensation. It is associated with a poor prognosis and increased risk of mortality. A diagnostic paracentesis should be performed in liver disease patients with- new-onset ascites, at the beginning of each hospital admission and when ascitic fluid infection (AFI) is suspected. The routine analysis includes cell count with differential, bacterial culture, ascitic fluid total protein and albumin. A serum albumin-ascitic fluid albumin gradient of ≥1.1g/dL confirms the diagnosis of portal hypertension. Ascites has been reported in children with non-cirrhotic liver disease like acute viral hepatitis, acute liver failure and extrahepatic portal venous obstruction. The main steps in management of cirrhotic ascites include dietary sodium restriction, diuretics and large-volume paracentesis. Sodium should be restricted to maximum of 2mEq/kg/d (max 90mEq/d) of sodium/day. Oral diuretic therapy comprises of aldosterone antagonists (e.g., spironolactone) with or without loop-diuretics (e.g., furosemide). Once the ascites is mobilized, the diuretics should be gradually tapered to the minimum effective dosage. Tense ascites should be managed with a large-volume paracentesis (LVP) preferably with albumin infusion. Therapeutic options for refractory ascites include recurrent LVP, transjugular intrahepatic porto-systemic shunt and liver transplantation. AFI (fluid neutrophil count ≥250/mm3) is an important complication, and requires prompt antibiotic therapy. Hyponatremia, acute kidney injury, hepatic hydrothorax and hernias are the other complications.

Effects of dietary sugar restriction on hepatic fat in youth with obesity.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the presence of fibrosis. Children with NAFLD are at higher risk of liver-related complications, metabolic dysfunction, and cardiovascular disease in adulthood. Many factors contribute to the escalating prevalence of NAFLD in the pediatric population, among which are an array of dietary patterns such as overnutrition, poor diet quality, and heavy consumption of fat and sugar, including fructose. Findings from an increasing number of epidemiological studies support a connection between high habitual sugar consumption and NAFLD, especially within the context of obesity, but these studies are not able to demonstrate whether sugar is a contributing factor or instead an indicator of an overall poor diet (or lifestyle) quality. To date, only four randomized controlled dietary interventions assessing the effects of sucrose/fructose restriction on hepatic fat fraction in youth with obesity have been published. The objectives of this review are to summarize the key findings from these dietary interventions to achieve a better understanding of the strength of the relationship between dietary sugar restriction and liver fat reduction, despite their inherent limitations, and to discuss the potential impact of weight loss and fat mass reduction on improvement in hepatic steatosis.

Optimal graft size in pediatric living donor liver transplantation: How are children different from adults?

Pediatric liver transplantation is an established treatment for end-stage liver disease in children. However, it is still posing relevant challenges, such as optimizing the graft selection according to the recipient size. Unlike adults, small children tolerate large-for-size grafts and insufficient graft volume might represent an issue in adolescents when graft size is disproportionate. Graft-size matching strategies over time were examined in pediatric liver transplantation. This review traces the measures/principles put in place to prevent large-for-size or small-for-size grafts in small children to adolescents with a literature review and an analysis of the data issued from the National Center for Child Health and Development, Tokyo, Japan. Reduced left lateral segment (LLS; Couinaud's segment II and III) was widely applicable for small children less than 5 kg with metabolic liver disease or acute liver failure. There was significantly worse graft survival if the actual graft-to-recipient weight ratio (GRWR) was less than 1.5% in the adolescent with LLS graft due to the small-for-size graft. Children, particularly adolescents, may then require larger GRWR than adults to prevent small-for-size syndrome. The suggested ideal graft selections in pediatric LDLT are: reduced LLS, recipient body weight (BW) < 5.0 kg; LLS, 5.0 kg ≤ BW < 25 kg; left lobe (Couinaud's segment II, III, IV with middle hepatic vein), 25 kg ≤ BW < 50 kg; right lobe (Couinaud's segment V, VI, VII, VIII without middle hepatic vein), 50 kg ≤ BW. Children, particularly adolescents, may then require larger GRWR than adults to prevent small-for-size syndrome. Age-appropriate and BW-appropriate strategies of graft selection are crucial to secure an excellent outcome in pediatric living donor liver transplantation.

Gut microbiota in chronic liver diseases in children

The impact of gut microbiota on the development of various diseases is of great interest to researchers. However, data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children are lacking.Purpose. To study the taxonomic diversity of the fecal microbiota in children with chronic liver diseases in comparison with healthy patients.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 target fragment of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The comparison group consisted of fecal samples of 34 apparently healthy children.Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. An analysis of the conducted studies showed that fecal samples of healthy children and patients with chronic liver diseases differ in bacterial diversity. The dominant taxa in healthy children were Neisseria flavescens, in patients with chronic liver diseases, the dominant taxa were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis. At the same time, Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis in fecal samples of patients with chronic liver diseases was 8 times as high.Conclusion. Studies have shown differences in the composition of the intestinal microbiota in healthy children and children with chronic liver diseases.

A great pediatrician and scholar devoting his whole life to pediatric infectious and digestive diseases—In memoriam of Professor Yongsui Dong

A great pediatrician and scholar devoting his whole life to pediatric infectious and digestive diseases—In memoriam of Professor Yongsui Dong

Multiple beneficial effects of 1-year nutritional-behavioral intervention on anthropometric and metabolic parameters in overweight and obese boys.

Childhood obesity is on the rise worldwide increasing the risk for metabolic, cardiovascular and liver diseases in children. Eating habits and lifestyle changes are currently the standard of care for treating pediatric obesity. Our study aimed to determine the impact of a dietary intervention based on the Mediterranean Diet (MD) and the Health Eating Plate, on anthropometric and metabolic parameters in obese and overweight boys. We studied 126 overweight/obese boys with anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire (FFQ) at baseline, at 6 and 12months after a nutritional-behavioral intervention. We observed a significant reduction in energy, macronutrients and micronutrients intakes. BMI-SDS significantly decreased after 1year with the proportion of obese boys decreasing by 33% and of overweight boys by 41%, while also all fat mass measures decreased both in obese and overweight individuals. In obese boys, ALT decreased significantly after 1-year nutritional intervention and these changes correlated with BMI-SDS reduction. Insulin-resistance and secretion indexes correlated with fat mass and BMI-SDS. In obese boys, significant changes were observed at 6months for insulin concentrations, 1/HOMA-IR and QUICKI. With regard to the lipid profile, significant decreases were observed for total and LDL cholesterol in obese boys. Metabolic and anthropometric risk factors in overweight and obese boys can be improved by a nutritional-behavioral intervention of 1-year duration.

The future of hepatology.

The field of hepatology has made impressive progress over its ~75 years of existence. Advances in understanding liver function and its dysregulation in disease, genetic determinants of disease, antiviral therapy, and transplantation have transformed the lives of patients. However, there are still significant challenges that require ongoing creativity and discipline, particularly with the emergence of fatty liver diseases, as well as managing autoimmune disease, cancer, and liver disease in children. Diagnostic advances are urgently needed to accelerate risk stratification and efficient testing of new agents with greater precision in enriched populations. Integrated, holistic care models should be extended beyond liver cancer to diseases like NAFLD with systemic manifestations or extrahepatic comorbidities such as cardiovascular disease, diabetes, addiction, and depressive disorders. To meet the growing burden of asymptomatic liver disease, the workforce will need to be expanded by incorporating more advanced practice providers and educating other specialists. The training of future hepatologists will benefit from incorporating emerging skills in data management, artificial intelligence, and precision medicine. Continued investment in basic and translational science is crucial for further progress. The challenges ahead are significant, but with collective effort, the field of hepatology will continue to make progress and overcome obstacles.

Intestinal Reg4 deficiency confers susceptibility to high-fat diet-induced liver steatosis by increasing intestinal fat absorption in mice

Regenerating gene family member 4 (REG4) is a novel marker for enteroendocrine cells and is selectively expressed in specialised enteroendocrine cells of the small intestine. However, the exact roles of REG4 are largely unknown. In this study we investigate the effects of REG4 on the development of dietary fat-dependent liver steatosis and the mechanisms involved. Mice with intestinal-specific Reg4 deficiency (Reg4 ΔIEC ) and Reg4-floxed alleles (Reg4 fl/fl ) were generated to investigate the effects of Reg4 on diet-induced obesity and liver steatosis. Serum levels of REG4 were also measured in children with obesity using ELISA. Reg4 ΔIEC mice fed a high-fat diet demonstrated significantly increased intestinal fat absorption and were prone to obesity and hepatic steatosis. Importantly, Reg4 ΔIEC mice exhibit enhanced activation of adenosine monophosphate-activated protein kinase (AMPK) signalling and increased protein abundance of the intestinal fat transporters, as well as enzymes involved in triglyceride synthesis and packaging at the proximal small intestine. Moreover, REG4 administration reduced fat absorption, and decreased the expression of intestinal fat absorption-related proteins in cultured intestinal cells possibly via the CaMKK2-AMPK pathway. Serum REG4 levels were markedly lower in children with obesity with advanced liver steatosis (p <0.05). Serum REG4 levels were inversely correlated with levels of liver enzymes, homeostasis model assessment of insulin resistance, low-density lipoprotein cholesterol, and triglycerides. Our findings directly link Reg4 deficiency with increased fat absorption and obesity-related liver steatosis, and suggest that REG4 may provide a potential target for prevention and treatment of liver steatosis in children. Hepatic steatosis is a key histological feature of non-alcoholic fatty liver disease, which is the leading chronic liver disease in children leading to the development of metabolic diseases; however, little is known about mechanisms induced by dietary fat. Intestinal REG4 acts as a novel enteroendocrine hormone reducing high-fat-diet-induced liver steatosis with decreasing intestinal fat absorption. REG4 may be a novel target for treatment of paediatric liver steatosis from the perspective of crosstalk between intestine and liver.

Cohort Profile: Shiraz Pediatric Liver Cirrhosis Cohort (SPLCCS).

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort's features, the included population's baseline characteristics, and primary outcomes are reported.

Stoss therapy versus weekly regimen of vitamin D in children with chronic liver disease: a randomized pilot study

BackgroundVitamin D, a hormone involved in the regulation of mineral homeostasis, protects skeletal integrity and modulates cell growth and differentiation. Recently, its potential antifibrotic effects have also been identified. Children with chronic liver disease mostly suffer from vitamin D deficiency. However, little knowledge is known regarding the optimum regimen that can be utilized effectively and safely to correct vitamin D deficiency in these patients and whether it could be effective in reversal or at least halting the progressive process of liver fibrosis. This study is conducted to answer these questions.ResultsTwenty-four children with chronic liver disease (13 boys and 11 girls) were included in the study. Their age ranged from 4.5 to 11.5 years with median age of 8 years. The aetiology of liver disease was heterogenous with autoimmune hepatitis, glycogen storage disease, or chronic hepatitis, and hepatitis C affects the majority. The patients were divided into two matched groups: group A (n:12) that received stoss parenteral intramuscular vitamin D3 (cholecalciferol) therapy (200,000 IU) once followed by 600 IU/day orally for 6 months (this is equivalent to the RDA as maintenance therapy) and group B (n:12) that received 50,000 IU/week oral vitamin D3 (cholecalciferol) therapy in divided daily doses adding on the maintenance dose 600 IU/day for the first 4 weeks followed by only 600 IU/day orally for the rest of the 6 months (5 months). Following vitamin D3 supplementation, in group A (vitamin D stoss therapy group) and group B (vitamin D oral therapy group), there were statistically significant improvement of Ca, alkaline phosphatase, and vitamin D levels, though there was no difference in between both groups. No significant correlation could be found between vitamin D changes and fibroscan changes in either group.ConclusionVitamin D therapy using stoss dose followed by oral therapy or oral vitamin D therapy from the start was equally safe and effective in improving the clinical and laboratory metabolic bone profile abnormalities. Vitamin D effect on liver fibrosis progression or reversion in children is still not understood, and further studies are needed in this field taking in consideration the various causes of liver disease in children.

Evaluating the non-invasive tools for assessment of liver fibrosis in children with intrahepatic cholestasis prior to partial biliary diversion: tertiary-center experience

BackgroundThe liver biopsy is an essential element of evaluating progression of liver disease in children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Allagille Syndrome (AGS). Several noninvasive techniques, including radiological imaging and blood biomarkers assay, can be used to evaluate liver stiffness.ObjectivesTo identify whether liver Transient elastography (FibroScan) and AST/PLT Ratio Index (APRI) could be reliable tools to assess the degree of fibrosis prior to partial biliary diversion (PBD).MethodsA prospective cohort in which all patients with PFIC and AGS who underwent PBD from July 2019 to July 2021 were included. Preoperative liver functions, pelvic-abdominal ultrasonography and FibroScan assessments were performed while intraoperative liver biopsy was obtained.ResultsEight patients with chronic cholestatic liver disease who were candidates for PBD due to intractable pruritus were enrolled, including PFIC (n = 6; 75%), and AGS (n = 2; 25%). The liver FibroScan results were similar to the liver biopsy histopathological assessment in 87.5% of cases. APRI ranged from 0.1 to 3.2 (median = 1.2). In four cases (50%), APRI was consistent with histological evaluation of liver samples. The FibroScan results were in concordance with APRI results in three patients (37.5%).ConclusionThe current cohort demonstrated that fibroScan was consistent with histopathology in 87.5% of patients, highlighting its value in determining the degree of liver fibrosis prior to surgery, whereas the APRI was only consistent with histopathology in half of cases.

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.

Role of genetic modification of the PNPLA3 gene in predicting metabolically unhealthy obesity and metabolic associated fatty liver disease in children

Introduction and aim. Single nucleotide variants (SNV) of the patatin‐like phospholipase domain‐containing protein 3 (PNP-LA3) gene play an important role in hepatic lipid remodeling and lipogenesis de novo, which is associated with the development of metabolically unhealthy obesity (MUO) and metabolic associated fatty liver disease (MAFLD). The aim of the study was to define the contribution of SNV PNPLA3 gene to the development of MUO, complicated by MAFLD in children. Material and methods. 200 obese children aged 6-18 years were examined. The main group (n=118) was represented by children with MUO. The control group (n=82) consolidated of children with metabolically healthy obesity (MHO). Whole genome sequencing (CeGat) was performed in 31 children of the main and 21 children of the control group. Results. Among obese children, 14 variants of SNV PNPLA3 (rs139051, rs34179073, rs2294918, rs139047, rs779127153, rs2076212, rs738409, rs738408, rs4823173, rs2072906, rs2076213, rs141106484, rs138736228) were identified, including SNV PNPLA3 g.44322818, not described in the dbSNP core database. The role of the following SNV PNPLA3 genotypes in the development of MUO complicated by MAFLD was revealed: rs738409 C/G (Relative risk (RR)=1.71); rs738408 C/T (RR=1.71); rs4823173 G/A (RR=1.57); rs2072906 A/G (RR=1.57) with Sensitivity (Se)=0.63 and Specificity (Sp)=0.72. Conclusion. The contribution to the development of MUO complicated by MAFLD in children is made by the linked association of genotypes: rs738409 C/G, rs738408 C/T, rs4823173 G/A and rs2072906 A/G out of 14 PNPLA3 SNVs diagnosed by us.

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.

Prevalence of non-alcoholic fatty liver disease in overweight and obese children seeking ambulatory healthcare in Nairobi, Kenya

BackgroundWhile linked to obesity and associated with an increased cardiovascular morbidity, non-alcoholic fatty liver disease (NAFLD) is an often-asymptomatic cause of chronic liver disease in children. Early detection provides opportunity...

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.

The Importance of New EBMT Criteria on the Diagnosis of Veno-Occlusive Liver Disease in Children.

Early recognition and specific therapy facilitate a favorable disease course in hepatic venous-occlusive disease (HVOD) following hematopoietic stem cell transplantation (HCT). Diagnostic and classification criteria, published by the European Society for Blood and Marrow Transplantation (EBMT), better account for clinical differences in disease presentation in pediatric populations. To compare the course of HVOD in children before and after the implementation of new EBMT criteria. The study retrospectively evaluates 26 HVODs in 179 children treated in a single HCT unit (Slovakia) comparing the period of 2014-2017 using the Baltimore and modified Seattle criteria with the period of 2018-2021, when new EBMT criteria were adopted. No difference in HVOD incidence (11.2% vs. 14.8%, p = 0.46) and in time of diagnosis post-HCT (15.6 days vs. 15.7 days, p = 0.75) was found. With EBMT criteria we observed more frequent anicteric disease at diagnosis (50% vs. 87.5%, p = 0.04), lower serum bilirubin at diagnosis (3.4 mg/dL vs. 1.23 mg/dL, p = 0.045), and non-significant trends of shorter defibrotide treatment (21.7 days vs. 15.6 days, p = 0.73), decreased mortality (30% vs. 6.2%, p = 0.10) and shorter hospitalization (73.1 days vs. 59.6 days, p = 0.54). Different time periods around the implementation of new criteria are evaluated, underling that pediatric EBMT criteria for post-transplant HVOD diagnosis appear more sensitive.

Diagnostic accuracy of inflammation and insulin resistance markers in non-alcoholic fatty liver disease in children

Background. Insulin resistance indices, in particular homeostatic model assessment of insulin resistance (HOMA-IR), and circulating cytokines are promising markers for noninvasive assessment of hepatocyte damage and metabolic risk in non-alcoholic fatty liver disease (NAFLD) in children and can be used to select pediatric patients at risk of adverse disease course. The purpose was to determine the diagnostic accuracy of insulin resistance markers and circulating cytokines in non-alcoholic fatty liver disease in children. Materials and methods. One hundred and seventy patients aged 6–17 (average of 12.15 ± 2.51) years were included in the study. Hepatic steatosis was determined by transient elastography. Patients were divided into 4 groups according to the presence of hepatic steatosis, non-alcoholic steatohepatitis (NASH) and obesity: group 1 — 37 obese children with NASH, group 2 — 53 patients with simple steatosis, group 3 — 65 obese children without steatosis, group 4 (controls) — 15 patients with normal weight without NAFLD. Anthropometric parameters, carbohydrate metabolism with the HOMA-IR calculation, cytokine profile were evaluated. Results. An increase in serum interleukin (IL) 6 and tumor necrosis factor (TNF) α levels in NAFLD children compared to the control group (p &lt; 0.05), a decrease in IL-10 level in patients with NAFLD (p &lt; 0.05), and an increase in TNFα/IL-10 ratio (p &lt; 0.05) in NASH children compared to obese patients without steatosis were demonstrated. In NAFLD children, an increase of HOMA-IR was found compared to the controls and obese patients without steatosis (p &lt; 0.05). The threshold value of HOMA-IR for the diagnosis of simple steatosis was 3.6 (sensitivity 78.6 %, specificity 52.0 %, area under the curve (AUC) 0.687), for the diagnosis of NASH — 4.9 (sensitivity 77.5 %, specificity 61.7 %, AUC 0.750). The threshold value of TNFα/IL-10 ratio for the diagnosis of NASH was 0.58 (sensitivity 75.7 %, specificity 65.7 %, AUC 0.716). Conclusions. The threshold values of HOMA-IR and TNFα/IL-10 ratio demonstrate high diagnostic accuracy and can be used for early non-invasive diagnosis of NAFLD in obese children and for differential diagnosis of simple steatosis and NASH.