Pediatric Gastroenterology, Hepatology & Nutrition最新文献

Purpose: This study aimed to establish and characterize patient-derived intestinal organoids (PDOs) from children with Crohn's disease (CD).

Methods: To generate PDOs, endoscopic biopsy specimens were obtained from non-inflamed duodenal bulbs of normal controls and CD patients. To verify the presence of PDOs, histological staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses were performed.

Results: PDOs were successfully established in normal controls (n=2) and CD patients (n=2). Hematoxylin and eosin staining of formalin-fixed, paraffin-embedded PDO sections revealed crypt and villus structures, whereas immunofluorescence staining with EpCAM and DAPI confirmed the epithelial-specific architecture of the PDOs. RT-qPCR results revealed a significant increase in Lgr5, Si, and Chga gene expression and a decrease in Olfm4 and Muc2 expression in CD patients compared to normal controls, suggesting altered stem cell activity and mucosal barrier function (p<0.05).

Conclusion: We successfully established and characterized PDOs in children with CD, providing a valuable tool for understanding the pathophysiology of the disease and evaluating potential therapeutic approaches. The differential gene expression of PDOs in CD patients might be caused by the complex interplay between epithelial adaptation and inflammation in the intestinal epithelium.

Helicobacter pylori infection is often acquired in early childhood. While most infected children remain asymptomatic, H. pylori can cause chronic gastritis, gastric ulceration, and, in the long term, gastric cancer. This article aimed to review different diagnostic and treatment options and discuss the challenges associated with applying the current guidelines in the real world. Relevant articles published from 2015 to August 2023 in the English language in PubMed and Medline electronic databases were extracted using subject headings and keywords of interest to the topic. References of interest in the selected articles were also considered. Invasive and noninvasive diagnostic tests have advantages but also disadvantages and limitations according to the clinical setting and age of the child. Guidelines recommend not performing diagnostic testing in children with long-lasting or recurrent abdominal complaints or cases of a family history of severe disease caused by H. pylori. However, parents regularly consult with the explicit demand to test for H. pylori because of them or a close family member experiencing severe gastric disease caused by H. pylori. In some situations, it may be challenging for the healthcare professional to stick to evidence-based guidelines and not consider "patient-centered care," with the risk of putting a trustful relationship in danger. Physicians may find it challenging not to perform diagnostic tests for H. pylori and prescribe eradication treatment in specific clinical settings when maintaining a trusting patient-physician relationship by applying this "patient-centered care" method when evidence-based guidelines recommend differently.

Purpose: Cytomegalovirus (CMV) infection affects the hepatic, neurologic, hematopoietic, respiratory, gastrointestinal, and other organs, resulting in a high mortality rate and long-term sequelae. It may cause acute or chronic hepatitis, or even lead to hepatic cirrhosis. Valganciclovir (VGCV) is an effective, safe, and well-tolerated treatment for congenital CMV infection, without any serious adverse effects. This study was conducted to evaluate the clinical, biochemical, and virological profiles of infants with CMV with intrahepatic cholestasis and to determine the outcomes with or without treatment with VGCV.

Methods: Twenty infants aged <6 months diagnosed with congenital CMV infection with evidence of intrahepatic cholestasis were included in this study. Randomization was used to divide the study participants into 2 groups. The control group (n=10) was treated with only supportive management, and the intervention group (n=10) was treated with oral VGCV at 16 mg/kg/dose 12 hours a day for 6 weeks plus supportive treatments. Physical examinations and biochemical, serological, and virological tests were performed at the time of diagnosis and at the end of 6 weeks and 6 months.

Results: The control and intervention groups were compared in terms of clinical and laboratory parameters such as jaundice, dark urine, pale stool, hepatomegaly, total bilirubin, aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, and CMV polymerase chain reaction load, which showed a significant reduction after treatment in the intervention group (p<0.05) with oral VGCV, with very few side effects, whereas the control group showed no significant changes.

Conclusion: Oral VGCV can be used to effectively treat CMV infection with intrahepatic cholestasis without notable side effects.

Purpose: To evaluate prolonged esomeprazole use in Japanese pediatric patients for reflux esophagitis (RE) maintenance therapy and prevention of gastric (GU) and/or duodenal ulcers (DU) while using non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA).

Methods: This multicenter, open-label, parallel-group, phase III study (NCT03553563) included patients who were administered esomeprazole according to body weight (10 mg/day [Groups 1 and 3] and up to 20 mg/day [Groups 2 and 4] for patients weighing 10-20 kg and ≥20 kg, respectively). Efficacy outcomes for Groups 1 and 2 (maintenance therapy for healed RE) and Groups 3 and 4 (prevention of long-term NSAID/LDA use-associated GU/DU) were the presence/absence of RE relapse and GU/DU recurrence, respectively.

Results: Esomeprazole as maintenance therapy was associated with a low RE recurrence rate, independent of body weight or dosage. Recurrence rates of RE were 0.0% and 5.3% for Groups 1 and 2, respectively. In patients previously diagnosed with GU and/or DU due to long-term NSAID/LDA use, the recurrence rates of GU/DU during weeks 0-32 were 11.1% and 0.0% in Groups 3 and 4, respectively.

Conclusion: Long-term use of 10- or 20-mg, once-daily esomeprazole demonstrated a favorable benefit-risk balance in preventing RE and suppressing recurrence of GU and/or DU secondary to NSAID or LDA therapy in Japanese pediatric patients. No new safety concerns were identified. Esomeprazole may be a viable option for managing RE and preventing GU and DU in Japanese pediatric patients.

Purpose: Liver cirrhosis is a major cause of hospital admission and mortality among children. Understanding the factors that influence disease severity is essential for preventing and reducing mortality. This study explored the association between hemoglobin levels and liver disease severity in children with cirrhosis.

Methods: This cross-sectional study included 326 children with cirrhosis admitted to Namazi Teaching Hospital between 2015 and 2020. Clinical data, Child-Turcotte-Pugh (CTP) scores, and pediatric end-stage liver disease/model for end-stage liver disease (PELD/MELD) scores were collected to assess disease severity. Anemia was defined based on age, sex, and hemoglobin levels.

Results: Among the children with cirrhosis, 275 (84.4%) were anemic, with a mean age of 5.4±4.8 years. The overall mean hemoglobin level was 9.2±2.1 g/dL. A significant inverse correlation was observed between hemoglobin levels and CTP and PELD/MELD scores in children with anemia (p<0.001). Moreover, lower hemoglobin levels were associated with more higher CTP classes (p<0.001).

Conclusion: According to the data analysis, a significant correlation was observed between hemoglobin level and the severity of liver disease, and hemoglobin level decreased with increasing severity of liver disease. According to CTP class, the mean hemoglobin level decreased progressively as the disease progressed. A comparison of the mean CTP scores between children with and those without anemia revealed that those with anemia had more severe disease than those without anemia.

Purpose: Human breast milk (HBM) contains immune components that produced and delivered from the mother along with nutrients necessary for the baby. MicroRNA (miRNA) is a small noncoding RNA molecule, that is used as an ideal biomarker for diagnosis and prognosis of various diseases and are more abundant in HBM. We analyzed and compared the immune components and miRNAs of HBM.

Methods: HBM were collected from 20 healthy breastfeeding mothers. We measured the amount of lactoferrin, lysozyme, and immunoglobulin A (IgA) and extracted the miRNAs from each breast milk samples. Next, the top 5 and bottom 5 expressed miRNAs were compared and analyzed based on the amounts of the 3 immune components.

Results: The mean levels and ranges of lactoferrin, lysozyme, and IgA were 6.33 (2.24-14.77)×10⁶ ng/mL, 9.90 (1.42-17.59)×10⁷ pg/mL, and 6.64 (0.48-20.01)×10⁵ ng/mL, respectively. The miRNAs concentration per 1 mL of skim milk was 40.54 (14.95-110.01) ng/μL. Comparing the bottom 5 and top 5 groups of each immune component, 19 miRNAs were significantly upregulated (6, 9, and 4 targeting lactoferrin, lysozyme, and IgA, respectively) and 21 were significantly downregulated (4, 9, and 8 targeting lactoferrin, lysozyme, and IgA, respectively). There were no miRNAs that were expressed significantly higher or lower in common to all 3 components. However, 2 and 3 miRNAs were commonly overexpressed and underexpressed, in the top 5 groups of lysozyme and IgA concentrations.

Conclusion: We identified the immune components and miRNAs in breast milk and found that each individual has different ingredients.

Purpose: For neonates admitted to the neonatal intensive care unit (NICU), appropriate nutritional assessment and intervention are important for adequate growth. In this study, we aimed to determine whether there were changes in the nutritional supply and growth status of premature infants hospitalized in the NICU after the introduction of the Nutrition support team (NST).

Methods: This study retrospectively analyzed premature infants admitted to the NICU for over 14 days. The average daily calorie, protein, and fat supply at 1 and 2 weeks after birth were compared before and after NST, and growth was evaluated by changes in length, weight, and head circumference z-scores at birth and 28 days after birth.

Results: A total of 79 neonates were included in the present study, with 32 in the pre-NST group and 47 in the post-NST group. The average daily energy supply during the first (p=0.001) and second (p=0.029) weeks postnatal was significantly higher in the post-NST group than in the pre-NST group. Lipid supply for the first week was significantly higher in the post-NST group than in the pre-NST group (p=0.010). The change in the z-score for length was significantly higher in the post-NST group than in the pre-NST group (p=0.049).

Conclusion: Nutrient supply and length z-score change increased significantly at 28 days after birth in the post-NST group. These results suggest that calorie calculators and NST activity can promote adequate growth and development in neonates.

Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis.

Methods: We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes.

Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively.

Conclusion: This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.

Purpose: The prevalence of nonalcoholic steatohepatitis (NASH) is increasing with the increasing prevalence of childhood obesity. Although NASH has a high risk of progression to liver fibrosis and cirrhosis, few studies have reported noninvasive markers for predicting hepatic fibrosis in children. This study aimed to evaluate and compare the diagnostic accuracies of serologic biomarkers and scoring systems for hepatic fibrosis in obese children with NASH.

Methods: A total of 96 children were diagnosed with NASH based on liver biopsy findings and divided into two groups according to the degree of liver fibrosis: mild (stage 0-1) or advanced (stage 2-4). Clinical and laboratory parameters and serum levels of hyaluronic acid and type IV collagen were measured. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) score were calculated.

Results: Among the noninvasive markers, only serum type IV collagen level and FIB-4 were significantly different between the two groups. The area under the receiver operating curve of each biomarker and scoring system was 0.80 (95% confidence interval [CI]: 0.70-0.90) for type IV collagen at an optimal cutoff of 148 ng/mL (sensitivity 69.8%, specificity 84.6%), followed by 0.69 (95% CI: 0.57-0.83) for APRI, 0.68 (95% CI: 0.56-0.80) for FIB-4, and 0.65 (95% CI: 0.53-0.77) for hyaluronic acid.

Conclusion: Type IV collagen as a single noninvasive serologic biomarker for hepatic fibrosis and FIB-4 as a hepatic fibrosis score are beneficial in predicting advanced hepatic fibrosis and determining proper diagnosis and treatment strategies before fibrosis progresses in obese children with NASH.

Purpose: Patients who receive frequent blood transfusions are at an elevated risk of developing hepatic fibrosis due to iron overload in the liver. In this study, we evaluated the effectiveness of transient elastography (TE) (FibroScan^®) for assessing liver fibrosis in patients with pediatric cancer.

Methods: We enrolled 106 consecutive cases of acute leukemia in individuals under 21 years of age. The participants were followed for 2 years. Based on their serum ferritin (SF) levels, the patients were divided into two groups: group 1 (SF≥300 ng/mL) and group 2 (SF<300 ng/mL). A liver FibroScan^® was performed, and a p-value of less than 0.05 was considered statistically significant.

Results: Among the various parameters in the liver function test (LFT), alkaline phosphatase was significantly higher in a subgroup of patients aged 5-8 years in group 2 compared to those in group 1. The indices of liver fibrosis determined by TE, including the FibroScan score, controlled attenuation parameter score, steatosis percentage, and meta-analysis of histological data in viral hepatitis score, as well as indirect serum markers of liver fibrosis such as the aminotransferase (AST)/alanine aminotransferase (ALT) ratio, Fibrosis 4 score, and AST to platelet ratio index, did not differ significantly between the two groups. The association between the TE results and LFT parameters was only significant for ALT.

Conclusion: Transfusion-associated iron overload does not have a significant correlation with severe liver fibrosis. FibroScan^® is not a sensitive tool for detecting early stages of fibrosis in survivors of pediatric leukemia.