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Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts., Methods: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management., Findings: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD., Conclusions: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD., Funding: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007)., Competing Interests: Declaration of interests M.-H.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. L.A.B. has received speaker fees from Novo Nordisk and is on the Steering Committee of ACTION Teens, a multicountry study of adolescent obesity sponsored by Novo Nordisk. All fees received are directed to L.A.B.’s hospital research cost center. M.K. is a consultant for Mirum and Medison Pharma. A.M. has received honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Janssen. N.B.H.N. has received honoraria for lectures and the role of advisory board member (Adolescents with Obesity) from Novo Nordisk. C.M. is chairman of the board and shareholder of DeFaire Medical AB, scientific advisor and shareholder of Oriflame Wellness AB, scientific advisor of Itrim AB, scientific advisor of and speaker for Novo Nordisk, scientific advisor of Rhythm, and speaker for Astra Zeneca, Semper, and Redeye. C.D.B. has received an independent research grant from Echosens. C.G. has acted as speaker for Merck, Gilead, Abbvie, and Novo Nordisk; has served as an advisory board member for Merck, Novo Nordisk, and Gilead; and has received unrestricted research funding from Theratechnologies Inc. M.T.A.-L. has obtained a grant from Novo Nordisk and has acted in an advisory capacity for MSD and Novo Nordisk and as speaker for Novo Nordisk, Gilead, and Abbie. J.M.P. has received consulting fees from Boehringer Ingelheim, MSD, and Novo Nordisk; speaking fees from Gilead, Intercept, and Novo Nordisk; travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk; educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD; and funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. J.-G.F. has received honoraria for lectures from Sanofi, Echosens, Abbott, Novartis, AstraZeneca, Hisky Medical Technologies, and Novo Nordisk; consulting fees from Allergan, Echosens, Novartis, and Terns; and research grants from Sanofi. S.S.S. serves on Mirum and Alberio advisory boards., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypoalbuminemia after liver transplantation (LT) is associated with acute kidney injury (AKI) and poor outcomes in adult LT recipients. This study was performed to examine the association between the postoperative serum albumin level and early postoperative outcomes of LT in children., Methods: This single-center retrospective review involved pediatric LT recipients (0-18 years old) treated from January 2013 to June 2020. All patients were admitted to PICU and received standard post-LT care protocol. We divided patients into low (< 30 g/L) and normal (> 30 g/L) groups based on postoperative albumin day 1 to 3., Results: Among 108 LT recipients, most had biliary atresia. The median age at the time of LT was 1.8 years [interquartile range (IQR), 1.5-5.7]. There were 18 patients in low albumin group [median albumin level, 27.9 g/L (IQR, 25.8-29.6) and 90 patients in normal albumin group [median albumin level, 34.5 g/L (IQR, 32.4-36.9). The low albumin group had significantly higher incidence of AKI, occurring in 20% of patients with a median onset of 2.5 days following LT (IQR, 1-5). Postoperative hypoalbuminemia (OR, 4.94; 95% CI, 1.32-18.47; p = 0.01) and a longer operative time (OR, 1.37; 95% CI, 1.01-1.47; p = 0.02) were independent risk factors for AKI by multivariable analysis. No significant differences between the two groups were found in other early postoperative outcomes., Conclusion: Postoperative hypoalbuminemia was associated with early postoperative AKI following LT in children but not with other worsening outcomes., (© 2024. The Author(s).)

Background and Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study., Approach and Results: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings., Conclusions: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To evaluate the prevalence of vertebral fracture (VF) in children with chronic liver disease (CLD) with and without liver transplantation (LT) and to determine the associated factors., Methods: A cross-sectional study was conducted. Patients aged 3-21 years with CLD both before and after LT were enrolled in the study. Lateral thoracolumbar spine radiographs were obtained and assessed for VF using Mäkitie's method. Clinical and biochemical data were collected., Results: We enrolled 147 patients (80 females; median age 8.8 years [interquartile range 6.0-11.8]; 110 [74.8%] in the LT group and 37 [25.2%] in the non-LT group). VF was identified in 21 patients (14.3%): 17/110 (15.5%) in the LT group and 4/37 (10.8%) in the non-LT group ( p =0.54). Back pain was noted in only three patients with VF. In the univariate analysis, a height z-score below -2.0 ( p =0.010), pre-LT hepatopulmonary syndrome ( p =0.014), elevated serum direct and total bilirubin levels ( p =0.037 and p =0.049, respectively), and vitamin D deficiency at 1-year post-LT ( p =0.048) were associated with VF in the LT group. In multivariate analysis, height z-score below -2.0 was the only significant associated factor (odds ratio, 5.94; 95% confidence interval, 1.49-23.76; p =0.012) for VF. All VFs in the non-LT group were reported in males., Conclusion: In children with CLD, VF is common before and after LT. Most patients with VF are asymptomatic. Screening for VF should be considered in patients with a height z-score below -2.0 after LT., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2024 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Objectives: This study aimed to assess the prevalence and identify predictors of hepatic steatosis and fibrosis in patients with juvenile idiopathic arthritis (JIA) during methotrexate treatment., Method: This cross-sectional study included JIA patients who had received methotrexate for > 1 year. Laboratory data including liver chemistry and lipid profiles were collected. Liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) were determined by transient elastography. Significant hepatic fibrosis was defined as LSM > 7 kilopascal (kPa), and hepatic steatosis was defined as CAP > 225 decibel/meter (dB/m). Logistic regression analysis was performed to identify predictors associated with hepatic steatosis and fibrosis., Results: Of 60 patients, 66.7% were female, and the median age (IQR) was 12.8 (10.6-15.0) years. The median duration of methotrexate usage (IQR) was 45 (22-85) months, and the median cumulative dose of methotrexate (IQR) was 3768 (1806-6466) mg. The median LSM (IQR) and CAP (IQR) were 4.1 (3.4-4.6) kPa and 191.0 (170.3-223.8) dB/m, respectively. No patients had transient elastography-defined hepatic fibrosis, whereas 21.7% had hepatic steatosis. A body mass index Z-score > 1 (OR 5.71 [95%CI 1.31-24.98], p = 0.021) and higher cumulative dose of methotrexate (OR 1.02 [95%CI 1.00-1.04], p = 0.041) were associated with hepatic steatosis, whereas the cumulative dose of steroids was not (OR 1.00 [95%CI 1.00-1.01], p = 0.097)., Conclusions: Hepatic steatosis is common among JIA patients receiving methotrexate, but none had transient elastography-defined hepatic fibrosis. Overweight/obese JIA adolescents and patients with a high cumulative dose of methotrexate are at risk for hepatic steatosis. Key Points •Long-term low-dose methotrexate usage and the concomitant use of other DMARDs did not increase the risk of hepatic fibrosis in JIA patients. •The prevalence of hepatic steatosis in JIA patients receiving methotrexate was higher than in a healthy pediatric population. •Overweight/obesity and a higher cumulative dose of methotrexate were predictors of hepatic steatosis., (© 2023. The Author(s).)

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV ( p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT ( p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.

To determine the clinical manifestations and outcomes of the coronavirus disease 2019 (COVID-19) in children who underwent liver transplantation (LT). A retrospective study was conducted at a transplant center in Thailand to include LT recipients aged < 18 years who had been infected with COVID-19. Out of a total of 54 children, there were 31 probable cases (57.4%) diagnosed using an antigen test kit and 23 confirmed cases (42.6%) diagnosed using polymerase chain reaction (14 children) or severe acute respiratory syndrome coronavirus 2 antigen (9 children). Approximately half of the children (25, 46.3%) received the BNT162b2 vaccine before the infection, with 3 and 2 doses in 5 and 18 children, respectively. While some had COVID-19 during the delta pandemic, most (46 children, 85.2%) were infected during the omicron pandemic, of which manifestations included fever (67.4%), cough (50%), and rhinorrhea (47.8%), and symptoms lasted approximately 3 days. None had severe diseases. All patients with mild-to-moderate disease were advised to continue the same immunosuppressive therapy as before the infection. Compared to unvaccinated children or children with one dose of the vaccine, fever was less common in those who received ≥ 2 doses (OR: 0.08; 95%CI: 0.01-0.57, adjusted for age and immunosuppressive types). Favipiravir was prescribed in most patients (90.7%). Only a few children had long COVID-19 or abnormal liver function tests lasting > 1 month (4 children, 7.4%, both). Pediatric LT recipients with COVID-19 during the delta and omicron variant pandemic reported mild symptoms despite undergoing immunosuppressive therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Timing for liver transplantation (LT) in biliary atresia (BA) children with end-stage liver disease (ESLD) is associated with all-cause mortality. The cut-off value of pediatric end-stage liver disease (PELD) score for LT consideration varies across institutions. We aimed to determine the cost-effectiveness of LT to prevent death among BA children registered on the waiting list with different severities of ESLD., Methods: Subjects were BA children aged < 12 years at a transplant center between 2010 and 2021. A decision tree was developed for cost-effectiveness analysis from a hospital perspective to compare all-cause death between patients initially registered with a low PELD score (< 15) and a high PELD score (≥ 15). Each patient's direct medical cost was retrieved from the beginning of registration until 5 years after LT, adjusted with an inflation rate to 2022 Thai Baht (THB)., Results: Among 176 children, 138 (78.4%) were initially registered with the high PELD score. The cost and mortality rate of the low PELD score group (THB1,413,424 or USD41,904 per patient and 31.6% mortality) were less than the high PELD score group (THB1,781,180 or USD52,807 per patient and 47.9% mortality), demonstrating the incremental cost-effectiveness ratio (ICER) of THB2,259,717 or USD66,994 per death prevented. The cost of early post-operative admission had the highest effect on the ICER. Considering the break-even analysis, cost among children initially registered at the low PELD score was also less expensive over time., Conclusions: Registration for LT at PELD score < 15 was more cost-effective to prevent death among BA children with ESLD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To evaluate duplex US findings of the HA in all three postoperative vascular (HA, PV, HV and IVC) complications of paediatric LT for early detection and some helpful secondary signs to determine these vascular complications., Materials and Methods: We collected data from 44 post-LT paediatric patients who underwent daily duplex US for seven consecutive days and three months after LT during January 2017-June 2020. Four duplex US parameters of the HA (extrahepatic PSV, intrahepatic PSV, RI and AT) were compared in patients with and without complications., Results: The PSV of the extrahepatic HA in patients with HA complications was higher than that in patients without complications (P value = 0.019). The PSV at 107.7 cm/s is the optimal cut-off parameter associated with HA complications [a sensitivity of 88.9% and a specificity of 80.0% (ROC area is 0.84)]. The intrahepatic RI was higher on the first day than on the last day and gradually decreased in patients without vascular complications (P value = 0.000). The intrahepatic PSV significantly decreased with time when comparing the first and last days in patients without PV and HV-IVC complications (P value = 0.014 and 0.038). In contrast, patients with vascular complications showed no significant decrease., Conclusion: The extrahepatic PSV relates to HA complications after paediatric LT but not PV and HV-IVC complications. Non-significantly decreased intrahepatic RI and PSV from the first day to the day of complication diagnosis may correlate with the occurrence of vascular complications., (© 2022. The Author(s).)

Background: Vitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited., Methods: This study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL., Results: Phase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3-27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7-22.8 ng/mL., Conclusion: Very high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction., (© 2023. The Author(s).)

Purpose: To evaluate the efficacy of Bacillus clausii in the treatment of pediatric constipation., Methods: A randomized, double-blind, placebo-controlled trial was conducted from January, 2021 to January, 2022 in children aged 1-5 years diagnosed with functional constipation according to Rome IV criteria. They were assigned to receive either B. clausii or placebo, once daily for four weeks. The primary out-come was treatment success (defined as ≥3 spontaneous stools per week and stool consistency grade ≥3 on Bristol stool chart). The secondary outcome was a comparison of stool frequency, consistency (defined by Bristol stool grade), and constipation-related symptoms., Results: This trial enrolled 38 children (B. clausii, n=20 and placebo, n=18). At 4 weeks, no significant difference was noted in the treatment success between B. clausii and placebo groups [45% vs 56%; P=0.52). On within-group analyses, the mean (SD) of Bristol stool grade increased in both the B. clausii [1.7 (0.5) to 2.8 (1.2); P=0.003] and placebo [1.8 (0.5) to 2.8 (1.2); P=0.01] groups. Significant increases in the treatment success rate (22% to 56%, P=0.01) and mean stool frequency per week [3 (0.9) to 4.2 (1.7), P=0.01] were pronounced only in the placebo group. The frequency of painful defecation and large fecal mass were also significantly decreased in both the groups. No serious adverse events were observed., Conclusions: A 4-week course of B. clausii as the sole treatment was not more effective than a placebo for the management of functional constipation in children aged 1-5 years.

Background: Cytomegalovirus (CMV) infection is the most common infection following pediatric liver transplantation (LT). Preemptive therapy (PET) is an approach to initiate antiviral treatment for asymptomatic early CMV viremia detected by surveillance testing. However, data on CMV infection after PET are scarce, and the optimal cut-off remains controversial. This study aimed to evaluate the incidence, risk factors, and consequences of CMV infection in pediatric LT using 2 different viral load (VL) cut-offs., Methods: We retrospectively reviewed patients aged 0-18 years who underwent LT at Ramathibodi Hospital between March 2001 and August 2020. Demographic data, CMV infection, CMV treatment, and consequences of CMV infection were collected. CMV viremia was monitored by a quantitative nucleic acid amplification test. Clinical outcomes were compared after starting antiviral therapy at a low (>400 but <2000 IU/mL) and a high VL cut-off (≥2000 IU/mL)., Results: A total of 126 patients were included. CMV infection was 71% (90/126), with an incidence rate of 5.5 per 1000 patient-day. Higher tacrolimus and prednisolone dosages were associated with CMV infection with an adjusted hazard ratio of 1.2 (95%CI 1.0-1.4, p = .02) and 2.4 (95%CI 1.9-3.4, p < .001), respectively. The consequences of CMV infection did not differ significantly for the low and high CMV VL cut-off groups., Conclusion: CMV infection in LT recipients is common and is associated with higher tacrolimus and corticosteroid dosage. Additionally, using the CMV VL cut-off at 2000 IU/mL to initiate antiviral therapy is practical and effective in preventing CMV disease., (© 2023 Wiley Periodicals LLC.)

Background: Southeast Asia is the endemic area of hepatitis E virus (HEV) infection. We aimed to determine the seroprevalence of the virus, its association, and the prevalence of chronic infection after pediatric liver transplantation (LT)., Methods: A cross-sectional study was performed in Bangkok, Thailand. Patients aged <18 years who had LT for >2 years underwent serologic and real-time polymerase chain reaction (rt-PCR) tests. Acute HEV infection was defined by the presence of positive anti-HEV immunoglobulin (Ig)M and HEV viremia from the rt-PCR. If the viremia persisted for >6 months, chronic HEV infection was diagnosed., Results: A total of 101 patients had a median age of 8.4 years [interqartile range (IQR): 5.8-11.7]. The seroprevalence of anti-HEV IgG and IgM was 15% and 4%, respectively. Positive IgM and/or IgG were associated with a history of elevated transaminases with an unknown cause after LT (p = 0.04 and p = 0.01, respectively). The presence of HEV IgM was associated with a history of elevated transaminases with an unknown cause within 6 months (p = 0.01). The two patients (2%) diagnosed with chronic HEV infection did not fully respond to the reduction of immunosuppression but responded well to ribavirin treatment., Conclusions: Seroprevalence of HEV among pediatric LT recipients was not rare in Southeast Asia. Since HEV seropositivity was associated with elevated transaminases of an unknown cause, investigation for the virus should be offered in LT children with hepatitis after excluding other etiologies. Pediatric LT recipients with chronic HEV infection may receive a benefit from a specific antiviral treatment., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Many children respond to medical treatment for gastroesophageal reflux disease (GERD). However, some may require invasive intervention for refractory disease. Due to the lack of prognostic tools in children, this study aimed to develop a predictive model for refractory GERD., Methods: A retrospective review was performed in children with symptoms of GERD at a university hospital. Refractory GERD was defined as an unresponsive disease after optimal treatment with medication for >8 weeks. The predictive model was constructed based on clinical features and 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring results., Results: A total of 205 children were included with a median (IQR) age of 0.6 (0.3, 2.0) years. Over half of the patients (59.5%) had motor disabilities. Forty-four children (21.5%) were diagnosed with refractory GERD and subsequently underwent fundoplication. Multivariable analysis suggested that the refractory disease was associated with motor disabilities (OR: 5.35; 95% CI: 2.06-13.91), recurrent aspiration pneumonia (OR: 2.78; 95% CI: 1.24-6.26), prematurity with an onset of GERD at a post-conceptual age <40 weeks (OR: 6.76; 95% CI: 1.96-23.33), and abnormal total reflux episodes according to age (OR: 2.78; 95% CI: 1.24-6.19), but not the acid exposure time or symptom association analysis. The predictive model for refractory GERD based on associated factors revealed an area under the ROC curve of 76.8% (95% CI: 69.2%-84.3%) with a sensitivity of 77.3% and a specificity of 64% when applying a cutoff score of ≥2.5., Conclusions: The predictive model, using clinical features and MII-pH, may be an additional tool to predict refractory GERD in young children., (© 2023 Japan Pediatric Society.)

Aim: Functional abdominal pain disorders (FAPDs) and functional constipation (FC) are the common functional gastrointestinal disorders in adolescents. We aimed to determine the prevalence of FAPDs and FC in adolescents using the Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms and the factors associated with these two functional gastrointestinal disorders., Methods: A survey for the prevalence of FAPDs and FC in adolescents was carried out at two high schools. A translated and validated Thai version of Rome IV Questionnaire of Pediatric Gastrointestinal Symptoms was used. Potential associated factors were also collected. Psychosocial problems were evaluated by using the Strengths and Difficulties Questionnaire., Results: A total of 1700 adolescents (55.5% females) with a mean age (SD) of 16.1 (0.9) years were enrolled. The prevalence of FAPDs and FC was 5.3% and 8.1%, respectively. The subtypes of FAPDs were functional dyspepsia (4.7%; postprandial distress syndrome 3.9% and epigastric pain syndrome 0.8%), irritable bowel syndrome (0.6%), abdominal migraine (0.4%) and functional abdominal pain not otherwise specified (0.3%). Multiple logistic regression analysis revealed that FAPDs were associated with female gender (odds ratio (OR) 3.3, 95% confidence interval (CI): 1.7-6.4), underlying allergic diseases (OR 3.2, 95% CI: 1.6-6.6) and concomitant emotional problem (OR 2.7, 95% CI: 1.2-5.9). No significant associated factors with FC were found., Conclusion: FAPDs and FC are common in adolescents. Postprandial distress syndrome is the most common subtype of FAPD. Associated factors for FAPDs may suggest hormonal, immune-related and psychological involvement in the disease pathogenesis., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Owing to the lack of data, we aimed to determine the etiology and outcome of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children in Southeast Asia., Methods: This retrospective study was conducted at a university hospital in Bangkok, Thailand. We included patients aged <18 years who were diagnosed with pancreatitis from 2000 to 2021., Results: Among 155 patients with pancreatitis, 21 (13.5%) were diagnosed with either ARP (n = 7) or CP (n = 14). Clinical manifestations of CP included chronic abdominal pain (n = 10, 71.4%), steatorrhea (n = 8, 57.1%), and diabetes mellitus (n = 1, 7.1%). Positive radiological findings compatible with CP were detected from an abdominal ultrasound, computed tomography, magnetic resonance cholangiopancreatography in 70%, 90.9%, and 92.9% of patients, respectively. Genetic, metabolic, and pancreaticobiliary causes were the major causes of ARP/CP (23.8% each) and the etiologies were unidentified in one-fifth of the patients. Patients with metabolic diseases who had AP were at-risk of developing ARP (hazards ratio [HR], 4.7, 95% confidence interval [CI]: 1.5-13.9). Children with ARP or CP were younger than those with AP (P = 0.04). Approximately two-thirds of patients with CP had growth faltering and they had more episodes of hospitalization due to acute attacks when compared to patients with ARP ( 4 [interquartile range [IQR], 3-6] vs. 3 [IQR, 2-3]; P = 0.02)., Conclusion: Genetic, metabolic, and pancreaticobiliary diseases were the common etiologies of ARP and CP among children living in a developing country in Southeast Asia. The burden of CP included malnutrition and frequent hospitalization. The findings emphasize the importance of an early etiological diagnosis and monitoring for pancreatic insufficiency in ARP/CP., (© 2022 Japan Pediatric Society.)

Background: Pediatric liver transplant (LT) candidates often miss complete varicella-zoster virus (VZV) vaccination before LT. We aimed to evaluate the immunogenicity of two doses of VZV vaccines in pediatric LT candidates younger than 2 years and persistence of its immunogenicity after LT., Methods: Patients aged 9-24 months were enrolled before LT. The first dose of VZV vaccine was given at 9 months, and the second dose was given at between 1 to 3 months later, and at least 4 weeks before LT. Varicella-zoster IgG (VZG) was used to detect immunoglobulin G antibodies to VZV and was reported as a test value (TV). A test value ≥ 0.9 was considered as seropositive. TV was measured at enrollment, 1 month after the first and the second dose of VZV vaccine, before LT, and 3 and 6 months after LT., Results: Fourteen children were enrolled in this prospective cohort study. The median age at the first and the second dose of VZV vaccine was 11.5 months (IQR 9-12) and 13 months (IQR 12-33), respectively. The seroconversion rate was 66.7% (8/12) and 70% (7/10) after the first and second VZV vaccine doses, respectively. Seven of nine patients who underwent LT had two doses of VZV vaccine. Six patients were seropositive before LT, which persisted at 3 to 6 months after LT. Of two patients who received only one dose, TV was not detected after LT., Conclusions: The two doses of VZV vaccine appeared to be more immunogenic than one dose in pediatric LT candidates aged less than 2 years., (© 2021 Japan Pediatric Society.)

Abstract: Diarrhea is common in adults after solid organ transplantation (SOT) and bone marrow transplantation (BMT), but data in children are limited. Therefore, we aimed to determine the incidence and etiology of pediatric early-onset diarrhea in post SOT and BMT.We reviewed children aged 6 months to 18 years who underwent liver transplantation, kidney transplantation or BMT between January 2015 and December 2019 with duration of diarrhea > 72 hours within the first 6 months after transplantation. Clinical data and diarrheal course were collected. Regression analyses were performed to define factors associated with the interested outcomes.Among 252 transplanted patients, 168 patients (66.6%) had 289 documented episodes of diarrhea. A diagnosis of 68.2% of post-transplant diarrhea remained 'indefinite'. Enteric infection in SOT and gastrointestinal acute graft-versus-host disease (GI-aGVHD) in BMT were the commonly identified etiologies. Among 182 episodes among BMT children, skin rash was more pronounced when compared the ones with diarrhea > 7 days vs ≤ 7 days (odds ratio [OR] 13.9; 95% CI 1.8, 107.6). Males were more likely to develop GI-aGVHD as compared to females (OR 8.9). We found that GI-aGVHD was more common in the ones with skin rash and the presence of white blood cells in stool examination (OR 8.4 and 3.1, respectively). Deaths occurred in 7.7%.Two-thirds of post-transplant children experienced at least one episode of early-onset diarrhea, of which the etiology mainly remains undefined. Various clinical factors of prolonged/chronic diarrhea and GI-aGVHD may help clinicians when managing these children., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Sarcopenia is common in cirrhotic adults and associated with waitlist mortality and worse outcome after liver transplantation. Psoas muscle mass has been used to define sarcopenia. Therefore, we aimed to determine the association between psoas muscle mass and waitlist mortality as well as post-transplant outcome in children with end-stage liver disease. Medical records and abdominal imaging of pediatric liver transplant candidates during 2010-2019 were reviewed. A subset of images was measured by two radiologists to determine inter-rater reliability. Psoas muscle surface area was determined at intervertebral lumbar disk 3-4 (L3-4) and 4-5 (L4-5) levels. PMI was calculated by psoas muscle surface area divided by height squared. We included 105 children, most with biliary atresia (84%). Patients with waitlist mortality had lower PMI compared to the ones who survived to transplantation (PMI at L3-4 levels 352.8 ± 162.5 vs. 416.8 ± 136.2 mm 2 /m 2 and at L4-5 levels 497.3 ± 167.8 vs. 571.4 ± 163.4 mm 2 /m 2 , both p = .04), but not in the multivariate analyses. For transplanted patients (n = 75), a higher rate of re-operation (39% vs. 15%, p = .03) and longer hospital stay (53 vs. 45 days, p = .02) were found in patients with lower PMI. Lower PMI is associated with higher re-operation rate and longer hospital stay following transplantation, but not waitlist mortality. PMI may be taken into consideration with other biomarkers to predict post-transplant complications., (© 2021 Wiley Periodicals LLC.)

Portal hypertension increases pressure in lymphatic ducts, which may lead to gastrointestinal (GI) protein loss. Reports have shown that adults with portal hypertension had resolution of protein-losing enteropathy after transplantation; but studies in children are very limited. We therefore aimed to evaluate GI protein loss in children with portal hypertension and defined changes after liver transplantation. Children aged 3 months to 18 years with portal hypertension and the age-matched healthy controls were enrolled during August 2018 to September 2019. Random fecal alpha-1 antitrypsin measurements were obtained at the initial visit, 3 months later, 1 week before, and 3 months after liver transplantation (if applicable). One or more positive test (> 0.795 mg/dL) was interpreted as a positive result. We enrolled 76 children (n = 38 in each group) with a median age of 15.5 months (interquartile range [IQR], 11.2-41.7), female 51%, and 92% with biliary atresia in the portal hypertension group. We noted GI protein loss in 4/38 children (10.5%) with portal hypertension, while none in the controls (p = 0.11). We found no significant differences on the markers of severity of liver disease and serum albumin between patients with vs. the ones without GI protein loss (p > 0.05). After liver transplantation, 2/4 patients with GI protein loss had undetectable loss. We found that, in a small group of children, 10.5% with portal hypertension had notable GI protein loss without significant relationships with the severity of liver disease.

Background: Liver transplant (LT) is a lifesaving treatment providing excellent clinical outcomes. However, data regarding behavioral and cognitive issues after LT are sparse in Asia. This study aimed to investigate behavior and cognitive problems among pediatric LT recipients., Methods: We used the Child Behavior Checklist (CBCL) to evaluate behavior problems and/or the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) to assess cognitive function. Participants were children aged 2 to 18 years who were treated with LT for at least 2 years., Results: We included 77 children with a median age of 7.8 years (interquartile range, 5.0-10.9). All children were evaluated with the CBCL, and 26 children were available for WISC-III assessment. Approximately one-third (34%) of the children had a total CBCL score above a clinical cutoff for significant behavior problems, and 29% of school-aged children had abnormal competence scores in a clinically significant range. Most of the evaluated children (17 of 26; 65%) had a normal full-scale intelligence quotient. Lower cognitive function was associated with having a single parent (P < .01). Higher behavior problems were associated with lower parental education level (P = .01) and correlated with longer post-transplant duration (Spearman's rho = 0.443; P < .001)., Conclusions: Significant numbers of children have behavior problems after LT. Most children have normal cognitive function, although a larger sample size is required to confirm this result. Long-term support for cognitive and behavior problems after LT should be implemented, particularly in children with single parents and lower parental education level., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although identifying cases in large administrative databases may aid future research studies, previous reports demonstrated that the use of the International Classification of Diseases, Tenth Revision (ICD-10) code alone for diagnosis leads to disease misclassification., Purpose: We aimed to assess the value of the ICD-10 diagnostic code for identifying potential children with biliary atresia., Methods: Patients aged <18 years assigned the ICD-10 code of biliary atresia (Q44.2) between January 1996 and December 2016 at a quaternary care teaching hospital were identified. We also reviewed patients with other diagnoses of code-defined cirrhosis to identify more potential cases of biliary atresia. A proposed diagnostic algorithm was used to define ICD-10 code accuracy, sensitivity, and specificity., Results: We reviewed the medical records of 155 patients with ICD-10 code Q44.2 and 69 patients with other codes for biliary cirrhosis (K74.4, K74.5, K74.6). The accuracy for identifying definite/probable/possible biliary atresia cases was 80%, while the sensitivity was 88% (95% confidence interval [CI], 82%-93%). Three independent predictors were associated with algorithm-defined definite/probable/possible cases of biliary atresia: ICD-10 code Q44.2 (odds ratio [OR], 2.90; 95% CI, 1.09-7.71), history of pale stool (OR, 2.78; 95% CI, 1.18-6.60), and a presumed diagnosis of biliary atresia prior to referral to our hospital (OR, 17.49; 95% CI, 7.01-43.64). A significant interaction was noted between ICD-10 code Q44.2 and a history of pale stool (P<0.05). The area under the curve was 0.87 (95% CI, 0.84-0.89)., Conclusion: ICD-10 code Q44.2 has an acceptable value for diagnosing biliary atresia. Incorporating clinical data improves the case identification. The use of this proposed diagnostic algorithm to examine data from administrative databases may facilitate appropriate health care allocation and aid future research investigations.

Background: Health-related quality of life (HRQoL) of liver transplantation (LT) recipients has been widely studied because of increased patient longevity. However, studies in developing countries are scanty. We aimed to evaluate psychometric properties of the Thai version of the PedsQL Transplant Module and used it to determine the HRQoL in LT children., Methods: We included children aged 2 to 18 years who underwent LT more than 1 year previously. The phase 1 study included a cognitive interview with 20 LT children and their parents using the Thai version of PedsQL Transplant Module and revised the module accordingly. Then, the finalized version was evaluated for psychometric properties in 50 LT children. In phase 2, HRQoL was evaluated in 52 LT children who did not participate in the phase 1 study., Results: In the Thai PedsQL Transplant Module, both parent report and child self-report had good internal consistency (α = 0.94 and 0.93, respectively) and substantial reliability (interclass correlation coefficient = 0.82 and 0.77, respectively). Median HRQoL scores from the parent report and child self-report were 80 (interquartile range [IQR], 70, 88) and 77 (IQR, 71, 88), respectively. From the parent report, lower HRQoL was associated with opportunistic viral infection (P = .004) and correlated with a greater number of immunosuppressive agents (ρ = -0.346, P = .014). However, none of these factors were significant according to the child self-report., Conclusions: The Thai PedsQL Transplant Module has satisfactory psychometric properties. Post-LT children have good HRQoL. To improve their HRQoL, specific attention should be focused on managing viral infection and optimizing immunosuppressive therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Bacterial infection has been identified as one of the most significant complications of liver transplantation (LT). Multidrug-resistant (MDR) gram-negative bacteria (GNB) infection remains problematic issue following LT in the adults. However, data in children are scarce. We aimed to examine the prevalence and associated factors of MDR-GNB infection among pediatric LT recipients.We performed a single-center retrospectively study of 118 children who underwent LT between January 2010 and December 2018. Data on the prevalence, clinical characteristics, types, and sites of MDR-GNB infection within 3 months after LT as well as the treatment outcomes were collected. Multidrug resistance was defined as acquired non-susceptibility to at least 1 agent in 3 or more antibiotic classes.In total, 64 (53.7%) patients developed 96 episodes of culture-proven bacterial infection with 93 GNB isolates. Moreover, there were 58 (62.4%) MDR-GNB isolates, with a predominance of Klebsiella pneumoniae (32.7%), Escherichia coli (31%), and Pseudomonas aeruginosa (10.3%). Interestingly, 10 (17.2%) isolates were determined to be carbapenem-resistant Enterobacteriaceae. The median time to MDR-GNB infection was 9 (interquartile range: 5-33) days. The most common type of infection was intra-abdominal infection (47.9%). In the multivariate analysis, the significant variables associated with post-LT MDR-GNB infection include exposure to third-generation cephalosporins (hazard ratio [HR]: 2.16, P = .023), operative time (hazard ratio [HR] 1.20, P = .009), and length of intensive care unit stay (HR 1.03, P = .049). With a focus on carbapenem-resistant Enterobacteriaceae infection, a pediatric end-stage liver disease score >21 was the only significant 6 variable in the multivariate analysis (HR 11.48, P = .024). The overall 3-month mortality rate was 6.8%.This study has highlighted the high prevalence rate of MDR-GNB infection after pediatric LT. Therefore, caution on the emergence of MDR-GNB infection should be paid in at-risk children. Moreover, knowledge regarding the prevalence of MDR-GNB infection and resistant patterns is essential for guideline development to prevent and minimize the risk of MDR-GNB infection in this group of patients.

Purpose: Pediatric acute liver failure (PALF) is a serious condition; however, data on PALF in developing countries are sparse, particularly concerning molecular diagnosis and liver transplantation (LT). This study aimed to determine the causes, outcomes, and prognostic factors of PALF., Methods: We retrospectively reviewed the medical records of children (age <15 years) with PALF diagnosed using the American Association for the Study of Liver Diseases criteria at our center from 2011 to 2016. The collected data included laboratory results, complications, outcomes, and potential factors associated with death and LT., Results: We included a total of 27 patients, with a median age of 2 years (interquartile range, 3 months to 4 years). Viral infection was the most common etiology (n=8, 30%), predominantly dengue infection (n=4). A total of 16 patients (59%) died and 11 patients survived (3 patients with LT). The prognostic factors associated with death or LT requirement were grade IV hepatic encephalopathy ( p <0.01), hypotension ( p =0.02), gastrointestinal bleeding ( p =0.03), increased intracranial pressure ( p =0.04), and higher peak serum lactate level ( p =0.01). Peak serum lactate ≥6 mmoL/L had a sensitivity of 79% and a specificity of 88% for predicting mortality or the necessity of LT., Conclusion: Viral infection was the most common cause of PALF. The mortality rate remained high, and a considerable number of patients required LT. In addition to several clinical factors, peak serum lactate could be a potential marker for predicting poor outcomes in PALF., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2020 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re-transplantation. TE is a non-invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05-1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children., (© 2019 Wiley Periodicals, Inc.)

Objectives: Previous meta-analyses in adults comparing a full single dose vs. split doses of polyethylene glycol with electrolyte solution demonstrated that the split-dose group had a higher rate of successful bowel preparation. To date, no similar study in children has been conducted. Therefore, we compared the efficacy of bowel preparation between the two regimens of polyethylene glycol with electrolyte solution in pediatric colonoscopy. The secondary outcomes were tolerability, acceptability, and compliance., Methods: An investigator-blinded randomized controlled trial was conducted to enroll children aged 2-18 years who underwent an elective colonoscopy at a teaching hospital between March 2018 and February 2019. Patients were randomly assigned to receive polyethylene glycol with electrolyte solution as a full single dose or two split doses. The Boston Bowel Preparation Scale was used for the efficacy (i.e. successful bowel preparation if score ≥ 6). Secondary outcomes were evaluated by using a standardized questionnaire., Results: A total of 45 colonoscopies (22 in the full single-dose and 23 in the split-dose group) were performed. Mean age was 9.2 years old (SD 4.4). We noted a higher rate of successful bowel preparation in the split-dose group (95% vs. 72%, P = 0.047). Significant higher rate of willingness to repeat the same protocol (83% vs. 36%, P = 0.002) and a trend of lower rate of nausea/vomiting (39% vs. 68%, P = 0.051) in the split-dose group were found., Conclusion: The split-dose regimen of polyethylene glycol with electrolyte solution for bowel preparation suggests superior efficacy, potential tolerability, and acceptability as compared to the traditional full single-dose regimen.

PTLD is a rare but potentially life-threatening condition, which shows a higher prevalence in children than in adults. From 129 children who underwent LT, we reported 5 cases with biopsy-proven PTLD at a single teaching hospital. Four patients had shared clinical presentations including fever, lymphadenopathy, and splenomegaly. They were noted to be given a prolonged course of IS due to the management of comorbid complications such as acute cellular rejection or severe food allergy or eosinophilic gastrointestinal disease. The other one patient presented with upper gastrointestinal bleeding from gastric mass during an early post-transplantation period. Notably, hypoalbuminemia was noted in all reported patients. Similar to previous studies, both EBV serology mismatch between the donor and recipient with high EBV viral load were noted in all except one case, whose EBV serology was unknown before LT. At least one episode of CMV reactivation was also observed in 3 of 5 patients prior to the PTLD diagnosis. The histopathology revealed 1 of 5 early PTLD, 1 of 5 polymorphic PTLD, and 3 of 5 monomorphic PTLD. The treatment included IS withdrawal, chemotherapy, and/or rituximab. One patient died of multiorgan dysfunction, one remains in complete remission, and three patients are either still on treatment or await response evaluation. Even though most of our reported PTLD cases had shared manifestations with fever, lymphadenopathy, splenomegaly, EBV serology mismatch, and high EBV viral load, various initial presentations such as respiratory symptoms, hypoalbuminemia, and prolonged use of IS from other causes such as significant food allergy were noted., (© 2019 Wiley Periodicals, Inc.)

Aim: Children with biliary atresia (BA) born in countries with temperate climate showed month-of-birth (MoB) predilection during cooler months. To date, no study on the MoB-BA association has been performed in a tropical country. Our aim was to define MoB variation in children with BA in a tropical country., Methods: We studied 150 children diagnosed with BA between January 1996 and April 2015 at a teaching hospital. MoB was defined by two categories based on the precipitation: rain and dry, and three categories based on the air temperature: high, average and low. We applied the country's population data on the number of births in each period as the expected proportions of birth., Results: A slightly higher proportion of BA children was born in the rainy months (52.7%); however, the difference was not significant compared to the general population's birth (P = 0.87). For the MoB based on the air temperature, no statistically significant difference was noted. Males with BA seemed to have a greater MoB variation compared to females, but this did not reach statistical significance., Conclusion: We could not find an association between MoB and BA in a tropical country. Multinational studies may aid in understanding the MoB-BA association in the tropical countries., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time-consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with γ-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and an experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: The diagnosis of cytomegalovirus-related gastrointestinal disease (CMV-GI disease) still requires histopathology, but biopsy is considered invasive. Stool CMV PCR has been reported in adults as an alternative method to diagnose this condition; hence, the results between studies are discrepant. Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have been carried out. Here, we evaluate the value of stool CMV real-time PCR in detecting CMV-GI disease among immunocompromised children., Methods: We enrolled immunocompromised patients aged younger than 20 years who presented with gastrointestinal symptoms at a teaching hospital during January 2015-March 2016. Stool samples were analyzed for CMV real-time PCR. All patients underwent esophagogastroduodenoscopy and colonoscopy with mucosal biopsy., Results: We performed stool CMV real-time PCR in 31 patients, but two could not undergo endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples showed inhibitors that interfere with the PCR testing and were precluded from the final analysis. Among 27 patients, we found CMV-GI disease in seven (26%) patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant association between stool and plasma CMV real-time PCR was also noted (P<0.001)., Conclusion: Stool CMV real-time PCR may be used as a noninvasive tool in the diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant correlation with stool CMV real-time PCR and also represents high diagnostic values.

Background: Gastrointestinal bleeding (GIB) is one of the potential causes of increased morbidity and mortality in immunocompromised patients, but data on characteristics of GIB in immunocompromised children are sparse., Objectives: This study aimed to identify the etiology, endoscopic, and histologic findings of GIB in immunocompromised children., Design: This was a retrospective descriptive study., Patients: We identified 33 patients (aged<20 years) and 45 GIB episodes related to GIB between January 2007 and April 2015 from a tertiary care and teaching hospital., Results: The mean age at endoscopy was 10.7±4.6 years. Most common indications for endoscopy were melena in upper GIB and hematochezia in lower GIB. The median delay of duration between GIB presentation to endoscopy was 3 days. All except one child had at least one endoscopic abnormality. The most common cause of upper GIB was cytomegalovirus (CMV)-related gastrointestinal disease (35%), followed by esophageal varices (26%), and the most common cause of lower GIB was CMV-related gastrointestinal disease (55%). Fourteen percent of patients died during upper GIB episodes and 15% died during lower GIB episodes., Conclusion: Among immunocompromised individuals aged younger than 20 years presenting with GIB, CMV-related gastrointestinal disease is the most prevalent in our study population. However, the etiology of immunocompromised state needs to be taken into consideration when evaluating these children presenting with GIB.

Immature gastric teratoma is an uncommon germ cell tumor of the stomach. We report a rare case of immature gastric teratoma in an infant with down syndrome with clinically presenting with hematemesis and severe anemia. Complete surgical resection remains the cornerstone of treatment .

Henoch-Schönlein purpura (HSP) is a multi-organ vasculitis involving skin, joints, gastrointestinal tract, and kidneys. The present study reported a 5-year-old boy presenting with intense abdominal pain, bloody diarrhea, and protein-losing enteropathy. Investigations for infectious enteritis were negative. Esophagogastroduodenoscopy showed swelling and erythematous mucosa with hemorrhagic spots at duodenal bulb to the third part of duodenum. Histopathology of endoscopic biopsies revealed non-specific duodenitis. HSP was suspected, based on duodenitis and the presence of inflammatory markers without identifiable causes. Corticosteroid was started resulting in marked improvement of his clinical symptoms. Two weeks later, he developed nephrotic-range proteinuria, thus kidney biopsy was performed. Renal histology was consistent with IgA nephropathy, supporting the diagnosis of HSP This report emphasizes that patients with HSP may not always show visible purpura, and the diagnosis requires a high index of suspicion. GI endoscopy and renal biopsy may be helpful for the diagnosis in selected patients presenting with atypical presentations.

Objective: To determine the efficacy of prophylactic pharmacotherapy on the short- and long-term outcomes of children with cyclic vomiting syndrome (CVS)., Material and Method: Medical records were reviewed in 32 children who were diagnosed with CVS between 2000 and 2013. Efficacy ofprophylactic medications was classified as good vs. no response after treatment for three to six months. Long-term outcome was evaluated inpatients who had been diagnosedfor > or =2 years and classiied as 1) excellent: no episode, 2) good: one to two episodes, and 3) poor: three episodes or more during the past year., Results: At three to six months after treatment, good response to amitriptyline was significantly higher than propranolol (73% vs. 36%, p = 0.04). Of the 24 CVS patients whohad been diagnosed > or =2 years, data was available in 19 patients (mean age, 11.3 +/- 4.9; and mean duration from diagnosis to follow-up, 6.3+3.3 years). Excellent outcome was achieved in seven, good in seven, and poor in five children. Overall, the favorable long-term outcome (good and excellent) was 74%. Most children (86%) who hadfavorable long-term outcome had good response to the prophylactic medications in the early period of treatment., Conclusion: Amitriptyline may be more effective than propranololforprophylaxis of CVS. However, a randomized controlled trial is required to confirm this result. Children with CVS have a relatively favorable long-term outcome, particularly those who initially responded well to the prophylactic medications.