OBJECTIVES:Physical exercise may improve muscle mass and functional capacity in cirrhosis. This randomized controlled trial evaluates the impact of an exercise-based regimen versus standard medical therapy (SMT) on frailty scores, clinical outcomes, body composition analysis (BCA), and myokines in children with cirrhotic liver disease (CLD). METHODS:Children (9-18 years of age) with CLD with five Fried's frailty criteria score >5 were randomly assigned to groups that received exercise training + SMT (n = 23) or SMT alone (n = 23). Exercise regimen included aerobic and resistance exercises for a total of at least 50 min/day for 3-5 days per week for 24 weeks. Frailty assessment was done at baseline, 12 and 24 weeks while myokines levels and BCA was evaluated at baseline and after 12 weeks. RESULTS:At 12 and 24 weeks, the delta change in frailty scores was significantly greater in the exercise group compared to the SMT group (p < 0.001). Frailty score <5 was achieved by 60% and 85% of the exercise group at 12 and 24 weeks, compared to 32% and 37% in the SMT group. At 12 weeks, the exercise group showed a significant delta reduction in myostatin levels compared to the SMT group (p = 0.02). Significant improvements were observed in skeletal muscle mass (SMM) and phase angle in the exercise group at 12 weeks. CONCLUSIONS:In this pilot trial, exercise regimen significantly improved frailty scores and SMM compared to the SMT. Larger trials are warranted to further evaluate the long-term benefits of exercise in pediatric cirrhotic population.

Background:Therapeutic plasma exchange (TPE) artificially lowers prognostic markers such as INR and bilirubin, complicating timely decisions regarding liver transplantation (LT) in acute liver failure (ALF). Aims:We aimed to utilize machine learning (ML) models for predicting response to TPE and to create an online clinical decision support tool. Methods:Children aged 2-18 years with ALF who underwent at least one TPE session were included. Data were retrieved from a prospectively maintained database which included clinical data and serial biochemical variables. Multiple classifiers (random forest, logistic regression [LR], gradient boosted trees, extreme gradient boosted trees [XGBoost], support vector machine [SVM]) were trained and evaluated. Results:Of the 511 pediatric ALF patients admitted during the study period, 139 underwent TPE. After excluding LT, 110 were included in the primary analysis. The ML classifiers had maximum accuracy at T2 (12-18 h post-first TPE) and T4 (12-18 h post the second TPE). Among the various ML classifiers evaluated, LR, SVM, and XGBoost demonstrated highest discrimination at T2 (area under the curve [AUC]: 0.802-0.812; sensitivity: 79.6-80.8%, specificity: 70.2-73.4%, and positive predictive value: 83-84.1%) with limited improvement after data augmentation using synthetic minority oversampling technique. The AUCs of these three ML models were slightly lower at T4 (0.722-0.783). These sets of models, trained separately for real-time prediction of TPE response at baseline, T2, and T4, were incorporated into a web-based tool to guide decision-making in pediatric ALF. Conclusion:ML models based on LR, SVM, and XGBoost trained on serial clinical and biochemical data, particularly those acquired 12-18 h after each TPE session, can provide clinically meaningful and timely predictions of response to TPE, thus assisting clinical decision-making in pediatric ALF.

BACKGROUND AND OBJECTIVE:ABO-incompatible (ABO-i) liver transplantation (LT) in children is increasingly used to address organ scarcity, but concerns about immunological, vascular, and biliary complications remain. With evolving desensitization strategies and emerging pediatric data, an updated meta-analysis comparing ABO-i and ABO-compatible (ABO-c) LT is warranted. METHODS:PubMed, Embase, and Scopus were searched from inception to June 2026 to include studies evaluating ABO-i versus ABO-c LT in recipients ≤ 18 years of age. Primary outcomes were comparison of 1-, 3-, and 5-year patient and graft survival between the two groups. Secondary outcomes included comparisons of vascular and biliary complications, rejection, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections, and post-transplant lymphoproliferative disease (PTLD). RESULTS:Seventeen studies were included. Patient survival was comparable between the two groups at 1 year (risk ratio [RR]: 0.97, 95% confidence interval [CI]: 0.94-1.0, p = 0.07), 3 years (RR: 0.98, 95% CI: 0.94-1.01, p = 0.22) and 5 years (RR: 0.97, 95% CI: 0.88-1.07, p = 0.50). Likewise, graft survival showed no significant differences. Incidence of vascular and biliary complications, acute rejection, CMV and EBV infection, and PTLD also did not differ significantly between groups. Antibody-mediated rejection (AMR) was significantly higher in ABO-i recipients (RR: 20.04, 95% CI: 3.25-123.56, p = 0.001), although this finding was based on only four studies. Overall, heterogeneity was low. Certainty of evidence was rated as very low, primarily due to the observational design of included studies and risk of bias. CONCLUSIONS:ABO-i LT in pediatric recipients demonstrates survival and complication outcomes comparable to those of ABO-c LT. However, very low certainty of evidence highlights the need for future well-designed prospective studies.

OBJECTIVES:This randomized controlled trial (RCT) aimed to evaluate the efficacy and safety of a rotational thromboelastometry (ROTEM)-guided transfusion strategy in children with decompensated cirrhosis presenting with severe coagulopathy and/or thrombocytopenia undergoing invasive procedures. METHODS:This was an open-label, RCT which included (i) children 6 months to 18 years of age with decompensated liver cirrhosis, (ii) international normalized ratio (INR) between 2.5 and 3.5 (for procedures other than liver biopsy) and 2-2.5 (for liver biopsy), and/or (iii) platelet count between 20 and 50 × 109/L listed for invasive procedures. An interactive web response system was used to randomize the patient. Blood component transfusions in both arms were administered according to a predefined criterion. RESULTS:A total of 363 invasive procedures in decompensated chronic liver disease patients were screened for inclusion into the study. Of these, 76 were randomized (38 in each group with comparable baseline parameters). The proportion of patients receiving any blood component transfusion was significantly lower in the ROTEM arm (76.3% vs. 100%, p = 0.001). However, the volume of total and individual blood components transfused was comparable between groups. There was no difference in procedure-related bleed and transfusion-related complications between the two arms. In our study, the total costs incurred were higher in the ROTEM group (p < 0.001). CONCLUSION:In this cohort of children with decompensated cirrhosis and severe coagulopathy, ROTEM-guided transfusion reduced overall transfusion exposure but did not decrease blood product volume and was not cost-effective under the applied thresholds. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05734001 (Clinicaltrials.gov); CTRI/2023/02/049779 (Clinical trials registry of India).

OBJECTIVES:This study aims to assess whether steroid-based regimen enhances the clearance of jaundice and improves native liver survival (NLS). METHODS:We included all infants with biliary atresia (BA) undergoing Kasai portoenterostomy (KPE) at our centre. The algorithm-initiated prednisolone was initiated if stools remained acholic. RESULTS:Of 127 infants, 70 formed the steroid group (SG) and 57 the historical cohort (HC). Jaundice clearance at 6 months was superior with steroids (61.4% vs. 38.6%; odds ratio [OR] 2.53, 95% confidence interval [CI] 1.23-5.19, p = 0.013). Kaplan-Meier analysis demonstrated improved 24-month NLS (log-rank p = 0.044) in SG. Multivariate analysis identified younger age at KPE (adjusted odds ratio [aOR] 1.021 per day, 95% CI 1.004-1.038, p = 0.016), lower pre-operative bilirubin (aOR 1.163, 95% CI 1.024-1.320, p = 0.020) and steroid use (aOR 2.13, 95% CI 1.001-4.53, p = 0.050) as independent predictors of success. CONCLUSIONS:Moderate-dose prednisolone after KPE enhances early bile drainage and prolongs native liver survival. Optimal benefit is achieved when surgery is performed at ≤70 days of age. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06447051 (Clinicaltrials.gov) https://clinicaltrials.gov/study/NCT06447051.

Purpose:Published data on pediatric gastroenterology, hepatology, and nutrition (PGHN) training centers in the Asia-Pacific region are limited. This study aimed to evaluate the infrastructure, resources, and training opportunities in PGHN centers across the region to inform future development of training programs. Methods:We conducted an international multicenter, cross-sectional survey among Asia-Pacific nations between August 2023 and July 2024. Results:A total of 43 responses were received from 11 countries. Most centers (58.1%) operated with ≤3 specialists, and trainees in these centers were less likely to receive formal supervision or participate in research. Procedural exposure varied significantly: although endoscopy was widely available, 50% of centers reported fewer than 100 colonoscopies performed annually. Access to training in specialized procedures was limited (pH/impedance, 48.8%; high-resolution manometry, 34.9%; intestinal ultrasound, 41.9%), with radiologists performing most liver biopsies and intestinal ultrasounds in many centers. Conclusion:This first comprehensive survey of PGHN training in the Asia-Pacific region identified considerable variations, with key challenges in training infrastructure and procedural exposure. Most centers operate with limited specialist numbers, impacting supervision and research opportunities, and many struggle to meet international volume-based training requirements for essential procedures. Enhanced regional collaboration and alternative training approaches may help address these gaps.

Wilson disease (WD) and autoimmune hepatitis (AIH) are leading causes of chronic liver disease in children and often present with overlapping clinical and immunological features, complicating early diagnosis. This retrospective study evaluated serum immunoglobulin G (IgG) and autoantibody profiles in 79 genetically confirmed, treatment-naive pediatric WD patients compared with 112 AIH controls. Elevated IgG (>1.1× upper limit of normal) was observed in 82.3% of WD patients, while 31.5% tested positive for at least one autoantibody, including anti-smooth muscle antibody, anti-nuclear antibody, and anti-liver kidney microsomal. Notably, 20.2% of WD patients met the simplified diagnostic criteria for AIH. Compared to AIH, WD patients had significantly lower IgG levels and less frequent autoantibody positivity. Histology revealed distinguishing features, with WD showing more steatosis and ballooning but less interface hepatitis and plasma cell infiltration. These findings highlight the potential for diagnostic misclassification. Comprehensive evaluation, including histology and genetic testing, remains critical to differentiate WD from AIH and guide appropriate therapy.

Abstract Pediatric liver transplantation (LT) has increased globally in number and improved in outcomes over the last two decades. This significant progress is due to advances in surgical expertise, improved intensive care, better immunosuppressive protocols, a deeper understanding of genetic and metabolic conditions, and the expansion of donor pools. Prognostic scores for children awaiting LT have also been refined. Young, underweight infants or children with extra-hepatic organ failures, pulmonary complications such as hepatopulmonary syndrome, advanced stage hepatoblastoma, and hepatocellular carcinoma are now increasingly considered for LT, with outcomes as favourable as those without these complications. Optimizing these children is essential to improve their outcomes. This review summarizes both traditional and expanded indications for LT, as well as pretransplant multidisciplinary strategies to optimize outcomes.

Purpose:Hepatic glycogen storage disease type IX (GSD IX) results from a deficiency of phosphorylase kinase. A noninvasive method of monitoring liver disease severity in this population is unavailable and liver biopsy remains the gold standard for classifying disease severity, particularly for liver fibrosis. Methods:We proposed 2 novel hepatic GSD IX-specific liver disease severity scoring systems: one that incorporated laboratory parameters ("novel lab-only score") and one that incorporated laboratory, abdominal imaging, and growth parameters ("novel comprehensive score"). We compared their performance with established scoring systems used for other liver diseases and liver biopsy to determine concordance. Results:Liver disease severity was assessed in 56 pediatric participants with hepatic GSD IX. The novel lab-only and comprehensive scores correctly differentiated between mild and severe liver disease in 72.4% and 66.7% of participants, respectively. The Pediatric Non-Alcoholic Fatty Liver Disease Fibrosis Score demonstrated the highest accuracy in liver disease severity classification, correctly differentiating between mild and severe liver disease in 82.4% of participants. Conclusion:Hepatic GSD IX requires longitudinal monitoring and liver disease severity prediction scores may be useful clinical tools to noninvasively grade the severity of liver disease. Liver biopsy remains an important part of clinical management to understand the extent of liver disease.

Objectives:The current study aimed to explore the prevalence, predictors and outcomes of infections in pediatric acute liver failure (PALF).Methods:Data were retrieved from a prospectively maintained database of patients admitted with PALF between January 2012 and June 2024. "Sepsis" was defined as the presence of systemic inflammatory response syndrome with suspected or proven infection. Patients with positive bacterial and/or fungal cultures were labeled as "culture-positive sepsis." Outcome variables included native liver survival (NLS) and overall survival (OS) at day 28.Results:A total of 422 patients of PALF were included in the study of whom 195 (46.21%) fulfilled the criteria of sepsis and 71 (16.8%) had culture-positive sepsis. Bronchoalveolar fluid (37/81, 45.7%) was the commonest site of culture positivity followed by blood (29, 35.8%). More than 80% of cultures grew Gram-negative organisms with a high prevalence of carbapenem (77.1%) and multidrug (60%) resistance. These organisms were sensitive to colistin and newer beta-lactam combinations. Intensive care unit (ICU) stay, mechanical ventilation, grade 3-4 hepatic encephalopathy and use of extracorporeal liver support systems were associated with culture-positive sepsis. Patients with culture-negative sepsis had lower NLS and OS, whereas patients with culture-positive sepsis had outcomes comparable with patients without sepsis. However, culture-positive severe sepsis patients had significantly lowered NLS (33.3%) and OS (42.9%) at day 28.Conclusion:There is a high prevalence of carbapenem and multidrug-resistant sepsis in PALF. ICU stay and use of extracorporeal support are factors independently associated with sepsis. While culture-positive sepsis did not significantly affect survival, patients with severe sepsis had lower NLS and OS.

OBJECTIVES:This study aimed to evaluate the impact of continuous kidney replacement therapy (CKRT) on the outcomes of pediatric acute liver failure (PALF). METHODS:This was a retrospective analysis of PALF presenting to a tertiary care pediatric hepatology center between January 2012 and August 2024. Cases of PALF where CKRT was initiated within 24 h of admission for nonrenal indications (hyperammonemia, hepatic encephalopathy [HE]) were identified and outcomes compared to a propensity-matched cohort of controls not receiving CKRT. The primary outcome measures were native liver survival (NLS) and overall survival (OS) at Day 28. RESULTS:A total of 448 patients with PALF were admitted during the study period, of which 94 had received CKRT. Thirty-eight (40.4%) of them who received CKRT for renal indications were excluded. The remaining 56 (59.6%) received CKRT for hyperammonemia and HE. The NLS in the CKRT and no CKRT groups were 46.4%, and 52.1%, respectively, while the OS in the two groups was 53.6%, and 61.3%, respectively. In the propensity-matched cohort (52 in each arm), there was a statistically insignificant trend toward higher NLS (46.2% vs. 36.5%, p = 0.304) and OS (53.8% vs. 44.2%, p = 0.291) in CKRT group compared to controls. Patients receiving CKRT had lower ammonia (p = 0.016) and bilirubin (p = 0.008) levels on Day 4, while international normalized ratio and lactate levels remained comparable. CONCLUSION:CKRT led to significant reduction in ammonia on Day 4 in PALF; however, this did not translate into improved NLS and OS.

Hypoglycemia, especially when recurrent or persistent, is an important indicator of inborn metabolic errors. Although commonly encountered by hepatologists, it continues to be a pandora's box as no consensus on the exact definition and diagnostic work up exists. Here, we present four interesting pediatric cases of varied age groups, presenting with hypoglycemia as their major symptomatology. We also attempted to provide a systematic diagnostic guide for a refined and targeted approach to inherited metabolic liver diseases presenting with hypoglycemia.