Update on the diagnosis and management of neonatal intrahepatic cholestasis caused by citrin deficiency: Expert review on behalf of the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Citrin deficiency is an autosomal recessive metabolic liver disease caused by mutations in the SLC25A13 gene. The disease typically presents with cholestasis, elevated liver enzymes, hyperammonemia, hypercitrullinemia, and fatty liver in young infants, resulting in a phenotype known as "neonatal intrahepatic cholestasis caused by citrin deficiency" (NICCD). The diagnosis relies on clinical manifestation, biochemical evidence of hypercitrullinemia, and identifying mutations in the SLC25A13 gene. Several common mutations have been found in patients of East Asian background. The mainstay treatment is nutritional therapy in early infancy utilizing a lactose-free and medium-chain triglyceride formula. This approach leads to the majority of patients recovering liver function by 1 year of age. Some patients may remain asymptomatic or undiagnosed, but a small proportion of cases can progress to cirrhosis and liver failure, necessitating liver transplantation. Recently, advancements in newborn screening methods have improved the age of diagnosis. Early diagnosis and timely management improve patient outcomes. Further studies are needed to elucidate the long-term follow-up of NICCD patients into adolescence and adulthood.

Postoperative hypoalbuminemia and outcomes of pediatric liver transplantation.

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.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Risk factors of cytomegalovirus infection after pediatric liver transplantation and effectiveness of preemptive therapy.

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.

Management and monitoring of pediatric inflammatory bowel disease in the Asia-Pacific region: A position paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group: Surgical management, disease monitoring, and special considerations.

Disease phenotype of pediatric inflammatory bowel disease (PIBD) in children from the Asia-Pacific region differs from that of children from the West. Many parts of Asia are endemic for tuberculosis, making diagnosis and management of pediatric Crohn's disease a challenge. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in Asia due to differences in disease characteristics and regional resource constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) that aims to provide an up-to-date, evidence-based approach to PIBD in the Asia-Pacific region. A group of pediatric gastroenterologists with a special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management, and monitoring. Attention was paid to publications from the region with special consideration to a resource-limited setting. This current position paper deals with surgical management, disease monitoring, immunization, bone health, and nutritional issues of PIBD in Asia. A special section on differentiating pediatric Crohn's disease from tuberculosis in children is included. This position paper provides a useful guide to clinicians in the surgical management, disease monitoring, and various health issues in children with IBD in Asia-Pacific region.

Cost-effectiveness analysis of liver transplantation in biliary atresia according to the severity of end-stage liver disease.

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.

Prediction of refractory gastroesophageal reflux disease in young children.

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.

Seroprevalence of hepatitis E virus after pediatric liver transplantation.

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 magnitude and management of functional constipation at pediatric gastroenterology clinics: A survey study of various countries.

BACKGROUND AND AIM: There have been no large-scale epidemiological study of functional constipation of pediatric gastroenterology services. This survey was undertaken to investigate the prevalence of functional constipation and magnitude of related problems in hospital settings of various countries as well as the practice of pediatric gastroenterologists in management of these conditions. METHODS: The survey was conducted by sending questionnaires to members of Societies for Pediatric Gastroenterology Hepatology and Nutrition of various continents. RESULTS: A total of 274 pediatric gastroenterologists from 41 countries participated in this study. Functional constipation accounted for overall 30% of patients attending pediatric gastroenterology outpatient clinics. In comparison with non-western countries, respondents from western countries reported significantly higher median annual numbers of new patients with intractable functional constipation (10 [4,25] vs 5 [2,10], P < 0.001), dyssynergic defecation (3 [0,15] vs 1 [0,4], P < 0.001), and colonic inertia (2 [0,5] vs 0 [0,1], P < 0.001). The use of high dose polyethylene glycol for fecal disimpaction was significantly more commonly among respondents from western countries, whereas rectal enema was significantly more favored in non-western countries. Respondents from different continents reported significant discrepancies in choices of investigations and management of patients with dyssynergic defecation and colonic inertia. CONCLUSIONS: Functional constipation is a major problem for pediatric gastroenterology outpatient services worldwide. There were significant variations in the investigations of choice and therapeutic management of functional constipation, intractable functional constipation, and related problems among pediatric gastroenterologists of different geographic regions.

Medical Management of Pediatric Inflammatory Bowel Disease (PIBD) in the Asia Pacific Region: A Position Paper by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology, and Nutrition (APPSPGHAN) PIBD Working Group.

Pediatric inflammatory bowel disease (PIBD) is rising rapidly in many industrialised and affluent areas in the Asia Pacific region. Current available guidelines, mainly from Europe and North America, may not be completely applicable to clinicians caring for children with PIBD in this region due to differences in disease characteristics and regional resources constraints. This position paper is an initiative from the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition (APPSPGHAN) with the aim of providing an up-to-date, evidence-based approach to PIBD in the Asia Pacific region, taking into consideration the unique disease characteristics and financial resources available in this region. A group of pediatric gastroenterologists with special interest in PIBD performed an extensive literature search covering epidemiology, disease characteristics and natural history, management and monitoring. Gastrointestinal infections, including tuberculosis, need to be excluded before diagnosing IBD. In some populations in Asia, the Nudix Hydrolase 15 (NUD15) gene is a better predictor of leukopenia induced by azathioprine than thiopurine-S-methyltransferase (TPMT). The main considerations in the use of biologics in the Asia Pacific region are high cost, ease of access, and potential infectious risk, especially tuberculosis. Conclusion: This position paper provides a useful guide to clinicians in the medical management of children with PIBD in the Asia Pacific region.

Prevalence of functional abdominal pain disorders and functional constipation in adolescents.

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.

Etiology and outcome of acute recurrent pancreatitis and chronic pancreatitis.

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.

Immunogenicity of varicella zoster vaccine in pediatric liver transplantation.

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.

Low psoas muscle index as an unfavorable factor in children with end-stage liver disease undergoing liver transplantation.

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 mm2 /m2 and at L4-5 levels 497.3 ± 167.8 vs. 571.4 ± 163.4 mm2 /m2 , 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.

A Surviving Child from Acute Liver Failure after an Ingestion of Cassia occidentalis Seeds.

Cassia occidentalis toxicity is thought to be uncommon; however, several cases have been described with acute hepatomyoencephalopathy with a high-mortality rate. We report a previously healthy, 2-year-old girl who developed acute liver failure after fresh seed ingestion. Without a specific antidote, we decided to implement supportive measures and medications including lactulose, sodium benzoate and N-acetylcysteine. The patient also experienced with cardiogenic shock and transient distal renal tubular acidosis, which were all spontaneously resolved. The liver chemistries returned to normal 3 months after the ingestion, without receiving liver assisted device or liver transplantation.

Immune responses to hepatitis B vaccination after hematopoietic stem cell transplantation in pediatric and young adult patients.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) recipients require hepatitis B (HBV) revaccination. Hepatitis B surface antibody (anti-HBs) seroconversion rates after revaccination range from 64% to 79% in these patients. The seroconversion rate and factors associated with non-seroconversion have not been clearly elucidated in pediatric and young adult recipients after HSCT. OBJECTIVES: To evaluate anti-HBs seroconversion rates in pediatric and young adult patients revaccinated after HSCT, and to identify factors associated with non-seroconversion. METHOD: The current study was prospective and cross-sectional. Post-HSCT recipients aged ≤25 years who had completed a course of three HBV revaccinations were recruited, and their anti-HBs titers were assessed. Non-seroconverted patients were administered a fourth vaccination. Those who subsequently remained seronegative were administered two additional vaccinations. Those who remained seronegative after all six vaccinations were defined as non-responders. RESULTS: A total of 118 patients were enrolled. The HBV-containing vaccines used included DTaP-IPV-HBV-Hib, DTwP-HBV-Hib, and monovalent vaccines. The anti-HBs seroconversion rate after three revaccinations was 82% (95% confidence interval [CI], 73.7-89.2). One patient (0.8%) was classified as non-responder. Factors associated with non-seroconversion after three revaccinations included cytomegalovirus (CMV) reactivation (odds ratio [OR] 10.63, 95% CI 1.16-97.00), anti-HBs seronegativity before HSCT (OR 7.01, 95% CI 1.55-31.78) and three DTwP-HBV-Hib revaccinations (OR 11.71, 95% CI 1.43-96.26). CONCLUSION: In the current study the anti-HBs seroconversion rate after three HBV revaccinations was excellent. CMV reactivation, anti-HBs seronegativity before HSCT, and three DTwP-HBV-Hib revaccinations were associated with non-seroconversion, but the non-responder rate was low.

Acute Gastroenteritis in Children of the World: What Needs to Be Done?

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography.

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.

Various initial presentations of Epstein-Barr virus infection-associated post-transplant lymphoproliferative disorder in pediatric liver transplantation recipients: Case series and literature review.

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.

Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants.

AIM: Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy. Our aim was to carry out a concise review of the literature, evaluate the impact of these common FGIDs on infants and their families, and provide an overview of national and international guidelines and peer-reviewed expert recommendations on their management. METHODS: National and international guidelines and peer-reviewed expert recommendations on the management of regurgitation, infantile colic and functional constipation were examined and summarised. RESULTS: Regurgitation, infantile colic and functional constipation cause frequent parental concerns, lead to heavy personal and economic costs for families and impose a financial burden on public healthcare systems. Guidelines emphasise that the first-line management of these common FGIDs should focus on parental education, reassurance and nutritional advice. Nutritional advice should stress the benefits of continuing breastfeeding, while special infant formulas may be considered for non-breastfed infants with common FGIDs. Drug treatment is seldom required, with the exception of functional constipation. CONCLUSION: By providing complete and updated parental education, reassurance and nutritional advice, healthcare professionals can optimise the management of FGIDs and related symptoms and reduce the inappropriate use of medication or dietary interventions.