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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Graft-versus-host disease may mimic eosinophilic gastrointestinal disorders in a pediatric patient who underwent bone marrow transplantation. • Clues for graft-versus-host disease include persistent hypereosinophilia and gastrointestinal symptoms that were unresponsive to conventional treatment of eosinophilic gastrointestinal disorders. • Ruxolitinib might be a treatment of choice for patients with a steroid-refractory disease. Eosinophilic gastrointestinal disorders (EGIDs) are well-documented entities in pediatric solid organ transplantation. However, the diseases are rare after bone marrow transplantation (BMT). We present an adolescent male with hemoglobin E-β-thalassemia who underwent BMT and developed chronic graft-versus-host disease (GVHD) mimicking EGIDs. Initially, the patient presented with a presumed diagnosis of eosinophilic gastroenteritis (subserosal type) and received corticosteroids for 12 weeks. Six months after corticosteroids cessation, he again developed abdominal pain, treated with corticosteroids, azathioprine, and a six-food elimination diet. Still, he later had similar symptoms with persistent hypereosinophilia. The patient was subsequently diagnosed with chronic GVHD after excluding various potential causes. Ruxolitinib also led to significant clinical improvement and the disappearance of eosinophilia. The differential diagnosis of chronic GVHD should be a concern in BMT recipients with persistent gastrointestinal symptoms and eosinophilia. Ruxolitinib may be a treatment option in children with a steroid-refractory disease. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • A significant number of children who underwent liver transplant had behavior problems. • Most common problems were affective problems in young children and somatic problems in children aged over 6 years. • Although more behavior problems were related to lower parental education level and longer post-transplant duration, lower cognitive function was associated with having a single parent. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • The PedsQL Transplant Module is reported on with respective psychometric properties. • Most children who underwent liver transplantation had a good quality of life. • Immunosuppressive drugs and opportunistic infections were associated with quality of life. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]