Biochemical and Anthropometric Indices of Insulin Resistance in Obese and Overweight Children with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.

The Ultrastructure of Hepatic Stellate Cell-Macrophage Intercellular Crosstalk as a New Morphological Insight into Phenomenon of Fibrogenesis in Pediatric Autoimmune Hepatitis.

The aim of the study was the pioneering retrospective ultrastructural evaluation of respective forms of hepatic stellate cells (HSCs) and analysis of their crosstalk with other adjacent nonparenchymal cells (NPCs), especially Kupffer cells/macrophages (KCs/MPs), in pediatric autoimmune hepatitis (AIH). METHODS: Ultrastructural assessment of the HSC population and NPCs was performed in transmission electron microscopy (TEM) using pretreatment liver biopsies from 25 children (8 boys and 17 girls) aged 4-17 with clinic-pathologically diagnosed untreated AIH. RESULTS: Submicroscopic evaluation allowed easy identification of numerous HSCs in the form of transitory cells, i.e., T-HSCs, accompanied by signs of fibrosis. T-HSCs included cells with features of activation initiation (iHSCs) and activation perpetuation (pHSCs), indicating high HSC activation plasticity. The pHSCs were markedly elongated and mainly showed a distinct loss of lipid cytoplasmic material, expanded and dilated channels of granular endoplasmic reticulum, and linear bundles of microfilaments beneath the cell membrane. They were surrounded by usually mature collagen fibers. Frequently activated KCs/MPs adhered directly to T-HSCs. Between them, tight intercellular junctions were formed by means of point desmosomes. CONCLUSIONS: Our qualitative TEM observations indicate a key role of T-HSCs in liver fibrogenesis in pediatric AIH, with the essential involvement of activated KCs/MPs that directly adhere to them. Tight intercellular junctions, being the ultrastructural exponent of the specific cellular mechanisms of the crosstalk between NPCs, can play a vital role in hepatic collagen fibroplasia. A better understanding of HSC population morphology at the ultrastructural level in AIH seems important not only to improve the disease morphological diagnostics but to also provide new insights into therapeutic interventions for the phenomenon of liver fibrogenesis.

Thrombospondin-2 as a potential noninvasive biomarker of hepatocyte injury but not liver fibrosis in children with MAFLD: A preliminary study.

Aim of the study: Metabolic-associated fatty liver disease (MAFLD) requires close monitoring due to its increased incidence and progression to fibrosis, cirrhosis and even hepatocellular carcinoma. The search for non-invasive markers to diagnose liver fibrosis is ongoing. The aim of our study was to evaluate the serum levels of growth differentiation factor-15 (GDF-15), thrombospondin-2 (TSP2), pentraxin 3 (PTX3) and angiopoietin-like protein 8 (ANGPTL8) in children with MAFLD. Material and methods: Fifty-six overweight/obese children with suspected liver disease were included in this prospective study. MAFLD was diagnosed according to the latest consensus. Vibration-controlled transient elastography (TE) was performed to detect clinically significant liver fibrosis. Serum concentrations of GDF-15, TSP2, PTX3 and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA). Results: Liver steatosis was diagnosed in abdominal ultrasound in 31 (55.36%) overweight/obese patients who were classified as the MAFLD group. Aspartate aminotransferase (AST)/platelet ratio (APRI) and liver stiffness measurement (LSM) values and TSP2 concentrations showed significantly higher values in patients in MAFLD than in the non-MAFLD group. TSP2 was significantly positively correlated with alanine transaminase (ALT), AST, γ-glutamyltransferase (GGT) and APRI in the study group. The receiver operating characteristics (ROC) analysis showed that the area under the curve (AUC) of LSM, APRI and serum TSP2 was significant for predicting MAFLD in obese children. In the multivariable regression model, LSM was the only significant parameter associated with the diagnosis of MAFLD in children. Conclusions: TSP2 may be a potential biomarker of hepatocyte injury in pediatric patients with MAFLD. None of the examined biomarkers were found to be effective non-invasive markers of liver fibrosis in children.

Chemerin as Potential Biomarker in Pediatric Diseases: A PRISMA-Compliant Study.

Adipose tissue is the main source of adipokines and therefore serves not only as a storage organ, but also has an endocrine effect. Chemerin, produced mainly in adipocytes and liver, is a natural ligand for chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and C-C motif chemokine receptor-like 2 (CCRL2), which have been identified in many tissues and organs. The role of this protein is an active area of research, and recent analyses suggest that chemerin contributes to angiogenesis, adipogenesis, glucose homeostasis and energy metabolism. Many studies confirm that this molecule is associated with obesity in both children and adults. We conducted a systematic review of data from published studies evaluating chemerin in children with various disease entities. We searched PubMed to identify eligible studies published prior to February 2022. A total of 36 studies were selected for analysis after a detailed investigation, which was intended to leave only the research studies. Moreover, chemerin seems to play an important role in the development of cardiovascular and digestive diseases. The purpose of this review was to describe the latest advances in knowledge of the role of chemerin in the pathogenesis of various diseases from studies in pediatric patients. The mechanisms underlying the function of chemerin in various diseases in children are still being investigated, and growing evidence suggests that this adipokine may be a potential prognostic biomarker for a wide range of diseases.

Serum concentration of fatty acids in children with obesity and nonalcoholic fatty liver disease.

OBJECTIVES: It has been suggested that circulating fatty acids (FAs) take part in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in children with obesity. The aims of this study were to evaluate the serum FA concentration in this pediatric population. METHODS: The prospective study included 80 children with obesity and suspected liver disease. Patients with viral hepatitis, autoimmune, toxic, and selected metabolic liver diseases were excluded. Criteria for NAFLD diagnosis included liver steatosis in ultrasound as well as elevated alanine transaminase (ALT) serum activity. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). Fasting serum FA concentrations were measured in all children using gas-liquid chromatography. RESULTS: NAFLD was diagnosed in 31 children. Total FA concentration was significantly higher (P < 0.01) in all obese children as well as in obese children with NAFLD compared with controls. In children with NAFLD, a significant, positive correlation was found between total FA concentration and cholesterol (R = 0.47, P < 0.01), triacylglycerols (R = 0.78, P < 0.001), and insulin (R = 0.45, P < 0.011). In a group of children with obesity, TILC correlated positively with saturated FA concentration (R = 0.23, P < 0.05). CONCLUSION: Data from the present study do support the hypothesis that FAs are potentially involved in the pathogenesis of NAFLD in children with obesity.

Autoimmune sclerosing cholangitis might be triggered by SARS-CoV-2 infection in a child - a case report.

The spectrum of liver involvement during coronavirus disease 2019 (COVID-19) is broad and mainly includes elevated liver enzymes and cholestasis. Severe acute respiratory syndrome corona- virus-2 (SARS-CoV-2) infection most often leads to a transient moderate increase in liver enzymes that is not accompanied by disturbances in the synthetic function of the liver. However, there is increasing evidence that SARS-CoV-2 infection is associated with the development of autoimmune disorders. The pathogenesis of autoimmune hepatobiliary diseases is not fully understood, taking into account genetic and environmental factors such as viral infections. We present a pediatric case of autoimmune sclerosing cholangitis (ASC), which was diagnosed 2 months after SARS-CoV-2 infection. To the best of our knowledge, ASC potentially triggered by COVID-19 has not been reported in pediatric patients. Further studies are needed to describe the clinical impact of the development of autoimmune liver diseases potentially associated with SARS-CoV-2 infection in pediatric patients. Our observations indicate that children with liver injury potentially caused by COVID-19 require long-term monitoring of liver function parameters.

Celiac Disease in Conjunction with Hereditary Fructose Intolerance as a Rare Cause of Liver Steatosis with Mild Hypertransaminasemia-A Case Report.

Celiac disease (CD) has been associated with several genetic and autoimmune disorders, but its association with hereditary fructose intolerance (HFI) is very rare. The possibility of an association between CD and HFI should be considered, especially in patients with a lack of improvement after a gluten-free diet. Children with HFI often present with a wide range of symptoms, however, data about a strong aversion to fruits and sweets may be helpful to establish the diagnosis. The diagnosis of HFI should be confirmed in genetic testing. Both CD and HFI may present with liver steatosis with hypertransaminasemia. In patients with these two disorders, the dietary restrictions of gluten and fructose improve clinical symptoms and protect them from secondary complications. We report the case of a child with the concurrence of these two disorders.

Total Keratin-18 (M65) as a Potential, Early, Non-Invasive Biomarker of Hepatocyte Injury in Alcohol Intoxicated Adolescents-A Preliminary Study.

BACKGROUND: Underage drinking is associated with health risk behaviors. Serum keratin-18 (CK18) levels are increased in liver diseases and may be biomarkers of outcome. The purpose of this study was to determine if the total CK18 (M65) or caspase-cleaved CK18 (M30) levels were different in adolescents admitted to hospital because of alcohol intoxication and controls with excluded liver diseases. METHODS: A prospective study included 57 adolescents after alcohol use and 23 control subjects. The concentrations of M30 and M65 in the serum samples were evaluated using an enzyme-linked immunosorbent assay. RESULTS: The median age was 15 (14-17) years and 49% were male. There were significant differences in M65 levels between the study and control groups (p = 0.03). The concentrations of M30 and M65 were insignificant in adolescents divided into subgroups according to blood alcohol concentrations (BAC). Significant positive correlations were found between BAC and M65 levels (p = 0.038; r = 0.3). In receiver operating characteristic (ROC) analysis M65 (cut-off = 125.966 IU/l, Se = 70.2%, Sp = 43.5%) allowed to differentiate between patients with and without alcohol intoxication (AUC = 0.66, p = 0.03). CONCLUSION: M65 appears to be a promising non-invasive biomarker of hepatocyte injury during alcohol intoxication in adolescents. Moreover, a higher concentration of M65 may indicate early organ injury before the increase in the activity of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-New Terminology in Pediatric Patients as a Step in Good Scientific Direction?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis, and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationships between NAFLD and MetS led to the set up in adults of a new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based on these findings, we propose a set of criteria, which may be useful to diagnose MAFLD in children and adolescents.

The role of chemerin in the pathogenesis of cholelithiasis in children and adolescents.

BACKGROUND AND AIM: Adipokines and hepatokines are proteins secreted by adipose tissue and the liver. To date, the levels of adipokines and hepatokines in cholelithiasis have only been evaluated in studies in adult patients. The purpose of our research was to assess the levels of circulating adipokines: chemerin, vaspin, progranulin, retinol-binding protein 4 (RBP-4) and hepatokine: fibroblast growth factor 21 (FGF-21) and to compare their concentrations in paediatric patients with and without cholelithiasis. METHODS: The prospective study included 54 children and adolescents diagnosed with gallstones and 26 controls. Fasting serum levels of adipokines and hepatokine were determined by enzyme-linked immunosorbent assays. RESULTS: The serum levels of chemerin, FGF-21 and RBP-4 were significantly higher in children and adolescents with gallstones compared to the control group. Elevated levels of triglycerides, RBP-4, and a homeostatic model for assessing insulin resistance (HOMA-IR) were observed in overweight or obese patients compared to patients with normal weight and cholelithiasis. Chemerin concentrations were increased in the normal-weight children and adolescents with cholelithiasis compared to the control group. Children and adolescents with gallstones and abnormal weight had significantly higher levels of chemerin, FGF-21 and RBP-4 than healthy controls. CONCLUSION: Elevated serum chemerin levels were significantly higher in non-obese patients with cholelithiasis than in non-obese controls, suggesting a potential role of chemerin in the development of cholelithiasis in children and adolescents.

Lack of change in serum sCD36 concentration in children with non-alcoholic fatty liver disease - A preliminary study.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is increasingly being recognized in the pediatric population, therefore, the search for non-invasive parameters to predict progression of NAFLD is of great interest. The aim of this study was to assess serum concentration of sCD36 in children with obesity and to determine its diagnostic value in pediatric NAFLD. PATIENTS AND METHODS: The study group consisted of 50 children with obesity aged 8-17.5 years, admitted to our Department because of suspected liver pathology. Selected liver diseases were excluded in the examined group. Anthropometry, laboratory tests (including the concentration of sCD36) and liver ultrasound, were performed in all subjects. RESULTS: NAFLD was confirmed in 16 out of 50 patients with obesity. There was significantly higher activity of ALT, AST, GGT, and increased waist-hip ratio WHR in individuals with NAFLD in comparison to non-hepatopathic children with obesity. We did not find a significant difference between sCD36 concentration in patients with obesity and NAFLD and non-hepathopathic patients with obesity. We also did not find a significant difference between sCD36 concentration in children with obesity in comparison to the control group and between mild (grade 1) vs. advanced (grade ≥2) steatosis. Correlation of sCD36 concentration with anthropometric, biochemical, and bioimpedance parameters in children with obesity was confirmed only with body fat percentage. CONCLUSIONS: sCD36 is not a suitable parameter to differentiate children with NAFLD from non-hepatopathic children with obesity and controls without obesity. Further studies on a larger pediatric population are needed to confirm these findings.

Can hepatokines be regarded as novel non-invasive serum biomarkers of intrahepatic lipid content in obese children?

PURPOSE: Hepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children. PATIENTS AND METHODS: The cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). RESULTS: The concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in 1H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant. CONCLUSIONS: FGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children.

Estimation of gamma-glutamyl transferase as a suitable simple biomarker of the cardiovascular risk in children with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and a risk factor for cardiovascular disease (CVD). Research conducted in adults has proven that GGT can also be an independent risk factor for CVD. The aim of this study was to ascertain if GGT can be regarded as a simple biomarker of cardiovascular risk in obese children with NAFLD. One hundred obese children, aged 7-17 years, with suspected liver pathology were admitted to our Department. Viral hepatitis and autoimmune, toxic and selected metabolic liver diseases were excluded. Anthropometry, laboratory tests, 1HMR spectroscopy and evaluation of the common carotid artery intima-media thickness (IMT) were performed in all subjects. NAFLD was confirmed in 38 obese patients. There was a significantly higher activity of GGT and ALT, the concentration of total and LDL cholesterol, waist circumference, left coronary artery IMT, mean IMT value and total lipids in 1HMRS in children with NAFLD in comparison to non-hepatopathic obese children. Logistic regression analysis indicated that GGT, total cholesterol, LDL-cholesterol, left IMT and waist circumference significantly affected the development of NAFLD in obese children. In ROC analysis only GGT, waist circumference and left IMT allowed to differentiate children with NAFLD from those without steatosis with GGT having the highest result (AUC=0.94). GGT activity in patients revealed weak or at the upper limit of statistical significance correlation with traditional cardiovascular risk factors: glucose level, waist circumference, BMI, total cholesterol, LDL-cholesterol and insulin level. This allows to suggest, that GGT might be a potential reliable, simple and non-invasive biochemical marker for estimation of cardiovascular risk in obese children with NAFLD. However, further studies on larger population are necessary to confirm that observation.

Increased serum concentration of ceramides in obese children with nonalcoholic fatty liver disease.

BACKGROUND: Hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD. METHODS: The prospective study included 80 obese children (aged 7-17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson's disease, alfa-1-antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children. RESULTS: NAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in 1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2-3). CONCLUSION: Elevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.

Predictive Role of Interleukin-18 in Liver Steatosis in Obese Children.

Introduction: Interleukin-18 (IL-18) is a proinflammatory cytokine associated with metabolic syndrome (MS). Nonalcoholic fatty liver disease (NAFLD) can be recognized as a feature of MS. Material and Methods: Serum IL-18 concentration was evaluated in serum of 108 obese children, determined with ELISA, and referred to degree of liver steatosis in USG or total intrahepatic lipid content assessed by magnetic resonance proton spectroscopy (1HMRS). Results: Fatty liver was confirmed in 89 children with USG and in 72 with 1HMRS. IL-18 concentration demonstrated significantly higher values in patients than in controls. Significant correlations between IL-18 and ALT, GGT, triglycerides, hsCRP, and the degree of liver steatosis were demonstrated. NAFLD children had significantly higher level of IL-18, ALT, GGT, HOMA-IR, waist circumference, and total lipids content in 1HMRS than other obese children. IL-18 level was also significantly higher in obese children with advanced liver steatosis. Measurement of serum IL-18 showed ability to differentiate children with fatty liver from those without steatosis. Conclusion: Elevated serum IL-18 concentration and its correlation with hepatocyte injury, systemic inflammation, and degree of liver steatosis support role in NAFLD pathomechanism. IL-18 can be considered to play a role in predicting advanced liver steatosis and fatty liver in obese children.

Hepatokines and non-alcoholic fatty liver disease.

Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone-binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver-derived proteins with the development and progression of NAFLD.

Hepatotoxicity caused by montelukast in a paediatric patient.

Montelukast is a selective and competitive cysteinyl leukotriene receptor antagonist (CystLTRA) which is increasingly used for the treatment of allergic asthma. Recently, hepatotoxicity has been reported with this drug in adult patients, but only one letter to the editor has reported a case of probable montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year-old boy, receiving treatment with montelukast, who developed hepatocellular injury. The exclusion of other causes of increased activity of aminotransferases (viral, metabolic, autoimmune), improvement after dechallenge, the morphological findings and previous reports of comparable cases support the diagnosis of montelukast-induced liver injury in this boy. Physicians should strictly analyse indications for this drug and be aware of potential drug-induced liver disease caused by this agent. Therefore, the periodical assessment of aminotransferases should be recommended during treatment with this leukotriene modifier.

Supplementation with long chain polyunsaturated fatty acids in treatment of atopic dermatitis in children.

Some recent studies indicate that unsaturated fatty acids, components of cellular membranes and precursors of immunomodulators, play a significant role in the pathogenesis of some symptoms of atopic dermatitis. Since they cannot be synthesized by the human body, they must be provided with nutrition as the so called exogenous fatty acids: linoleic (a precursor of arachidonic acid) and α-linolenic acid (a precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Their deficiency facilitates the development of some disorders, e.g. of the cardiovascular system or of the nervous system, or becomes the cause of intensification of ailments in their course e.g. pruritus and dryness in atopic dermatitis. Though clinical examinations to date confirm the efficacy of fatty acid supplementation in treatment of atopic dermatitis, their results are not explicit.

[Frequency and causes for hospitalization of children with cholelithiasis - own observations]. / Czestosc i przyczyny hospitalizacji dzieci z kamica zolciowa - obserwacje wlasne.

THE AIM: of this study was to assess the incidence and the cause of hospitalization of children with cholecystolithiasis. MATERIAL AND METHODS: A retrospective analysis was carried out using medical data of children and adolescents treated in the Department of Pediatrics, Gastroenterology, and Pediatric Allergology of Bialystok Medical University. The analysis included causes of hospitalization, its course and accompanying illnesses. During the 4 years of analysis, 47 children (17 boys, 30 girls), aged from 7 months to 18 years, with the diagnosis of cholecystolithiasis were treated. The comprised 1.18% of children hospitalized with gastrointestinal disorders. RESULTS: Cholecystolithiasis without complications was diagnosed in 29 children (61.7%), with cholecystitis in 13 (27.7%), choledocholithiasis was diagnosed in 5 children (10.6%). In 11 children (23.4%) the complication presented in form of acute pancreatitis. In 23 children (48.9%) factors predisposing to chorocholelithiasis were identified. In 20, the following were considered to be a possible significant factor: in 7 children there was a positive family history (14.9%), in 6 children (12.8%) - it was obesity, in 3 children (6.4%) lipid metabolic errors: prematurity and parenteral feeding in 2 children (4.3%) and spherocytosis in 2 children (4.3%). Apart from the above, cholelithiasis was diagnosed in two children with hypothyreosis and in two with Down's Syndrome. In treatment of 20 children (42.6%) antibiotics were prescribed and in 4 children (8.5%) endoscopic sphincterotomy was performed. 25 children (53.2%) were referred for laparoscopic cholecystectomy. In 16 children (34.0%), treatment with ursodeoxycholic acid was recommended. CONCLUSIONS: Cholecystolithiasis is a rare cause of hospitalization in pediatric departments. However, it occurs in even the youngest children. It usually runs without complications, but there is a certain risk of serious complications. In the differential diagnosis of abdominal pain, cholelithiasis should be taken into account, even in the youngest children. Special consideration should be given to the premature, with low birth weight and extremely low birth weight.