Journal of Pediatric Gastroenterology and Nutrition最新文献

Objectives: A clinical decision support tool (CDST) endorsed by The American Gastroenterological Association predicts likelihood of inflammatory bowel disease (IBD) remission in adults based on the advanced therapy selected. In children who are given these same therapies, predictors of response may differ from those in adults. The aim of this study is to establish the CDST's ability to predict remission in a pediatric IBD population treated with non-anti-tumor necrosis factor (TNF) biologics.

Methods: A single center retrospective review of IBD patients 2-21 years of age who received either vedolizumab (VDZ) or ustekinumab (UST) between 2018 and 2023 was performed. Subjects were either biologic naïve or had prior anti-TNF exposure. Baseline clinical characteristics were used to generate a CDST score. This score was compared to week 52 outcomes after starting VDZ or UST in the full cohort, divided by IBD diagnosis, and medication choice. A dichotomized cut-off score of > or ≤19 indicating high or low probability of steroid free clinical remission (SFR) was then used in the same analysis as well as groups separated by anti-TNF exposure status.

Results: One hundred seventy subjects were included. SFR at Week 52 of VDZ or UST was achieved in 108/170 (64%) of patients. SFR at Week 52 was significantly associated with CDST score in the full cohort (p < 0.001), in UC (p = 0.0015) and in CD (p = 0.043) subjects. SFR at Week 52 was significantly associated with dichotomized CDST cut-off score in full cohort (p < 0.001), UC (p < 0.005) and CD (p < 0.021) subjects. CDST score >19 had high sensitivity for predicting SFR at Week 52 in full cohort and when separated by disease state. In the anti-TNF exposed cohort, SFR at Week 52 was significantly associated with dichotomized CDST cut-off score of 19 (p < 0.0037). No significant association was seen in anti-TNF naive cohort. When separated by medical therapy, significant association seen with both continuous (p < 0.001) and dichotomized (p < 0.001) CDST score and SFR in patients treated with VDZ. No significant association was seen with patients treated with UST.

Conclusions: The CDST appears to have applicability for predicting week 52 SFR in children with UC or CD. CDST score of >19 is a highly sensitive cut point for predicting SFR in our pediatric IBD patients.

Objectives: Autoimmune hepatitis (AIH) presents as hepatitis, chronic or acute liver failure. Liver fibrosis may progress to liver cirrhosis. Pharmacological treatment aims to preserve liver function and induce remission. Transient elastography (FibroScan®, TE) has already been applied in many chronic liver diseases for non-invasive liver stiffness/fibrosis assessment. We aimed to evaluate the usefulness of liver stiffness measurement (LSM) in relation to liver fibrosis on biopsy, selected clinical features and laboratory markers of liver function in the largest paediatric AIH cohort studied.

Methods: We included 86 children with AIH (41 females) with a mean age of 14 years with AIH. Thirty-seven patients were naïve, and 49 had been previously pharmacologically treated. All patients underwent diagnostic or monitoring liver biopsy and LSM on TE. In selected cases, upper gastrointestinal (UGI) endoscopy was performed to search for oesophageal varices (EV). The relationship between LSM and fibrosis stage was analysed statistically. The optimal cut-off values of LSM were calculated to predict individual fibrosis stages and the presence of EV using the area under the receiver operating characteristic curve (AUROC).

Results: In our study, LSM was highly accurate in assessing fibrosis staging. LSM strongly correlated with liver fibrosis r = 0.81, p < 0.0001. TE discriminated patients with severe fibrosis (F ≥ 3) from others with excellent sensitivity and specificity-AUROC of LSM was 0.95 with an optimal cut-off point of 8.3 kPa. Similar results were produced when analysing naïve and treated patients. In addition, LSM showed prognostic value in predicting EV with AUROC of 0.77.

Conclusions: TE can be accurately and reliably used in children with AIH to diagnose and monitor liver fibrosis and its complications as portal hypertension. TE may help to identify patients with severe fibrosis who may require UGI surveillance, therapy modifications and possibly liver transplantation.

Objective: To investigate the diagnostic utility of abdominal shear wave elastography (SWE) in pediatric celiac disease (CD) by assessing mesenteric and terminal ileal stiffness and its association with serologic activity, histologic severity, and gluten-free diet (GFD) duration.

Methods: In this prospective study, 84 children with CD and 80 matched healthy controls were evaluated. Mesenteric and terminal ileal stiffness values were measured using SWE. CD patients were stratified by GFD duration (short-term: ≤6 months vs. long-term: >6 months) and tissue transglutaminase immunoglobulin A (tTG-IgA) levels. Diagnostic performance was determined using ROC curves.

Results: Mesenteric and ileal SWE values were significantly higher in CD patients than controls (p < 0.001 for both). Mesenteric stiffness demonstrated an area under the ROC curve (AUC) of 0.81 with an optimal cut-off of 9.03 kPa, while ileal stiffness showed an AUC of 0.83 with a cut-off of 9.71 kPa. Subgroup analysis revealed no significant difference in baseline Marsh scores between the short-term and long-term GFD groups (p = 0.305), despite a dramatic decline in tTG-IgA levels in the long-term group (p < 0.001). Elevated stiffness persisted in both newly diagnosed and GFD-treated patients compared with controls (all p < 0.001). No significant correlations were observed between SWE values and concurrent tTG-IgA levels or Marsh subtypes (all p > 0.05).

Conclusion: Increased mesenteric and ileal stiffness in children with CD likely reflect transmural involvement and structural remodeling beyond the mucosal injury. These findings demonstrate that SWE has good diagnostic utility and may serve as a valuable complementary noninvasive tool in the evaluation and clinical monitoring of pediatric CD.

Objectives: Biliary strictures (BS) remain a common and serious complication after pediatric liver transplantation (pLT), potentially leading to recurrent cholangitis and graft failure. Prompt diagnosis and appropriate management are essential to improve outcomes.

Methods: This retrospective, single-center study included 1454 pediatric liver transplants performed between January 2013 and December 2021. BS were classified as anastomotic strictures (AS), non-anastomotic strictures (NAS), or intraoperative technical misadventure (ITM). Cases involving both AS and NAS were classified under the BOTH group. A standardized percutaneous transhepatic cholangiography drainage (PTCD)-based protocol was applied: mild strictures were treated with PTCD alone, whereas severe strictures required balloon dilatation (BD) with external drainage. Surgical revision was performed when guidewire passage failed. Outcomes included stricture resolution, recurrence, and graft survival.

Results: BS occurred in 120 patients, with AS accounting for 63.3%, NAS & BOTH for 31.7%, and ITM for 5.0%. The overall incidence of BS declined significantly from 12.38% (2013-2016) to 7.07% (2017-2021). PTCD ± BD achieved an 85.7% resolution rate in AS, while surgical reanastomosis was successful in all refractory cases. NAS & BOTH were associated with significantly lower graft survival and showed limited response to both minimally invasive and surgical treatments.

Conclusions: Minimally invasive approaches, particularly PTCD ± BD, combined with timely surgical intervention, is effective for AS after pLT. However, NAS & BOTH remain challenging and are associated with inferior graft outcomes, underscoring the need for improved early detection and the development of novel therapeutic strategies.

Objectives: Adalimumab is commonly used to induce and maintain remission in pediatric Crohn's disease (CD). However, data on the efficacy and safety of high-dose adalimumab in this population are limited. This study aimed to evaluate the therapeutic effectiveness and safety of weekly high-dose adalimumab (80 mg) in pediatric CD patients.

Methods: This multicenter retrospective study included pediatric patients with CD who received adalimumab 80 mg weekly for more than 30 days following suboptimal response to standard dosing between 2014 and 2023. Clinical and biochemical outcomes, treatment durability, and adverse events (AEs) were assessed at predefined time points. Regression analyses were used to explore predictors of sustained corticosteroid-free remission (SCFR) and clinical response.

Results: Thirty-eight patients (71% male; median age 16.3 years [interquartile range, IQR: 14.3-16.9]) underwent dose intensification. Ileocolonic CD was observed in 53%, and 29% had perianal disease. Clinical remission at 12 months was achieved in 50% of patients. Among the 27 patients (71%) with available adalimumab trough concentrations (ATC), 74% reached a therapeutic level (≥7.5 µg/mL) at 1 year. No significant predictors of SCFR or clinical response were identified. Early post-intensification drug levels predicted 12-month remission (AUC  = 0.76), with an optimal threshold of 11.3 µg/mL (sensitivity 85%, specificity 67%). Treatment was de-escalated in 5% and discontinued in 26% due to primary nonresponse. AEs occurred in 13%, mainly mild dermatologic reactions.

Conclusions: Weekly 80 mg adalimumab appears to be an effective and well-tolerated intensification strategy in pediatric CD patients with pharmacokinetic loss of response. Further prospective studies are needed to confirm these findings and guide optimal use.

Objectives: Clinically, recurrent polyp growth is a characteristic feature of pediatric Peutz-Jeghers syndrome (PJS) patients. However, the clinical characteristics of pediatric PJS patients grouped by postoperative recurrence time remain undefined. Furthermore, differences in clinical features between serine/threonine kinase 11 (STK11)-positive and -negative patients, and the influence of STK11 mutation types on polyp recurrence time need to be elucidated. Our study aimed to characterize pediatric PJS based on postoperative polyp recurrence time and STK11 mutation status.

Methods: We collected clinical data from 74 pediatric PJS patients diagnosed at Hunan Children's Hospital over the past decade. STK11 genomic profiling was performed using Sanger sequencing combined with multiplex ligation-dependent probe amplification (MLPA) or whole exome sequencing (WES). Variables associated with gastrointestinal polyp recurrence were identified through least absolute shrinkage and selection operator (LASSO) regression, followed by multivariate logistic regression analysis of significant variables.

Results: All 74 pediatric PJS patients who experienced polyp recurrence post-polypectomy were stratified by recurrence time (>3, 1-3, and ≤1 year). Notably, 49.2% (31/63) of STK11-positive (STK11^pos) patients recurred within ≤1 year after polypectomy, while 81.8% (9/11) of STK11-negative (STK11^neg) patients with recurrence >3 years after polypectomy. LASSO and multivariate logistic regression identified multiple jejunal polyps (odds ratio [OR]: 4.18, 95% confidence interval [CI]: 1.09-15.98) and giant small bowel polyps (OR: 4.06, 95% CI: 1.15-14.34) as independent risk factors for recurrence ≤1 year after polypectomy. Compared to STK11^neg patients, STK11^pos patients, especially when combined with a positive PJS family history exhibited significantly earlier symptom onset, higher gastrointestinal giant polyp burden, and higher polyp burden in the jejunum/colon versus ileum. Analysis of 63 STK11^pos patients revealed diverse mutation types/sites and identified 15 novel pathogenic variants. STK11^pos patients with de novo mutations exhibited a significantly higher incidence of hematochezia, along with a greater overall burden of giant polyps in the colon. No significant association was found between major mutation subtypes (frameshift, missense, deletion, and nonsense) and recurrence time, though missense mutations showed a trend toward earlier recurrence.

Conclusions: This study reveals distinct clinical profiles across polyp recurrence intervals and between STK11-positive and -negative patients, while delineating the STK11 mutation landscape in pediatric PJS. These findings provide the genomic resource for pediatric PJS, offering critical insights into disease mechanisms and clinical management.

Following COVID-19, paediatric diabetic ketoacidosis (DKA) incidence and severity rose. We report a 2020-2024 cluster of four DKA-associated acute liver failure (ALF) cases at the largest UK paediatric hepatology unit. None had known diabetes. Presentations: one perianal abscess; three reduced consciousness, requiring intubation. Standard UK DKA protocol was started. Admission liver functions were normal. By day 4, all developed cardiovascular instability and ALF with liver injury, coagulopathy, metabolic acidosis, and hyperlactataemia. All required inotropes and haemofiltration. Three arrested; two died. Both autopsies showed centriacinar necrosis, with macro- and micro-vesicular steatosis. The two survivors normalised liver function. Viral, immune, and metabolic studies were unremarkable. This cluster suggests a novel, severe hepatic phenotype complicating paediatric DKA. Plausible mechanisms include ischaemic hepatitis and drug injury on a background of diabetes-related mitochondrial vulnerability. Earlier recognition of type 1 diabetes and awareness of hepatic complications may reduce morbidity and mortality.

Objectives: Children with inflammatory bowel disease (IBD) have an increased risk of developing kidney disorders, which may cause significant kidney function impairment (SKI) or lead to chronic kidney disease (CKD). In this study we aimed to provide insights in causes and diagnoses of SKI cases and to provide recommendations for pediatric gastroenterologists for children with IBD and SKI.

Methods: Cases of SKI in children with IBD (<19 years) were collected from the international, prospective PIBD-SETQuality Safety Registry. A monthly survey was sent to participating pediatric gastroenterologists to report cases of SKI (defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m²). Additionally, a panel consisting of 16 members (including experts in pediatric IBD and nephrology) rated the most likely cause of the cases and formulated recommendations for screening, follow-up and referral for children with IBD and SKI.

Results: Between November 1, 2016 and December 31, 2023, 42 cases of SKI were eligible for analysis. Tubulo-interstitial nephritis (TIN) was the most common diagnosis (n = 15). Sixteen (38%) cases were confirmed with renal biopsy (10 cases of TIN). Twelve patients developed CKD. IBD medication was the most frequently reported cause (n = 15), however, there was low concordance between panelists about the most likely etiology (Fleiss' kappa 0.143 and 0.102).

Conclusions: This is the first prospective study to report cases of SKI in children with IBD. SKI may lead to CKD. Confirming the etiology of the SKI proved to be very challenging. The study provides recommendations for screening and follow-up of SKI in children with IBD.

Objective: To compare isolated liver transplantation (LT) for cystic fibrosis (CF) versus other indications and versus combined liver-lung transplantation (CLLT) for CF in children and identify factors associated with survival.

Methods: We compared clinical and survival data after first isolated LT for CF versus other indications and versus CLLT for CF in children (<18 years) using United Network for Organ Sharing data (02/2002-12/2024).

Results: A total of 157 pediatric CF transplant recipients were included (LT: 145; CLLT: 12). Isolated CF LT recipients had higher total bilirubin (TB) than CLLT (median 1.6 vs. 0.7 mg/dL, p = 0.02). A higher proportion of CF transplant recipients with high TB levels (≥1.5 mg/dL) had ascites, encephalopathy, and required life support compared to those with low TB levels (<1.5 mg/dL). CF LT demonstrated superior patient survival versus CF CLLT (log-rank test, p = 0.02; 5-year: 89.1% vs. 72.2%), but inferior versus non-CF LT (log-rank test, p < 0.001; 5-year: 91.5%). Multivariable Cox regression showed increased risk of patient mortality and liver graft loss in CF CLLT recipients compared to isolated CF LT recipients (hazard ratio [HR] = 2.92, 95% confidence interval [95% CI]: 1.20-7.07, p = 0.02 and HR = 2.56, 95% CI: 1.09-5.98, p = 0.03, respectively) and recipients with higher TB levels (HR = 1.05, 95% CI: 1.01-1.10, p = 0.008 and HR = 1.05, 95% CI: 1.01-1.09, p = 0.008, respectively), when adjusting for recipient age, albumin and international normalized ratio (INR) at time of LT, ICU status, and liver graft type. Multivariable Cox regression of isolated LT recipients showed increased risk of patient mortality (HR = 2.03, 95% CI: 1.41-2.93, p < 0.001) and liver graft loss (HR = 1.54, 95% CI: 1.13-2.11, p = 0.006) for CF compared to non-CF etiologies, when adjusting for recipient age, albumin, INR, and TB at time of LT, ICU status, and liver graft type.

Conclusion: Isolated LT for CF was associated with superior survival compared to CLLT for CF, but inferior survival compared to LT for non-CF indications. Higher TB in CF may be a marker of inferior outcomes post-LT.