OBJECTIVES:The hepatology committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to provide education on key aspects of paediatric hepatology. Here we provide recent developments in the understanding, diagnosis and clinical consequences of portal hypertension (PHT) in children and young people, an area in which evidence remains scarce and fragmented. METHODS:In 2024, an EPSGHAN 3-day monothematic conference on paediatric PHT, held in Dublin (Ireland), brought together international experts in PHT. The first sessions of the conference were dedicated to PHT classification, pathophysiology, epidemiology, diagnostic dilemmas and major complications. Lectures have been integrated to provide an up-to-date overview of clinical practice. RESULTS:Opening sessions addressed the definition and classification of paediatric PHT, highlighting key differences between cirrhotic and non-cirrhotic causes. Advances in diagnostic imaging, the role of non-invasive tests and biopsy limitations are reviewed. Subsequent discussions focused on the mechanisms and management of major complications, including renal impairment, encephalopathy, cardiopulmonary dysfunction and endocrine consequences. Nutritional challenges and the interaction between PHT and gut-liver axis were emphasised as possible determinants of outcomes. CONCLUSIONS:This report summarises the key learning points of the first part of the meeting. These discussions set the foundation for defining research priorities and improving early recognition and multidisciplinary care strategies.

BACKGROUND:Chronic liver disease (CLD) affects 2-10 per 10 000 children. While prior evidence links CLD to lower cognitive ability, its impact on school readiness remains unclear. OBJECTIVE:To study the association between early-onset chronic liver disease (CLD; <5 years) and school readiness at age 5. DESIGN:A population-based cohort study using linked health and education data from the Education and Child Health Insights from Linked Data project in England. Children born between 2002 and 2012 with teacher assessments at age 4-5 years (2007/2008-2016/2017) were included. CLD diagnoses were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th revision and Operating Procedure Codes Supplement 4 hospital codes. Multivariable regression assessed standardised developmental outcomes in up to seven domains. RESULTS:Of 5 084 671 pupils, 0.1% (n=3672) were diagnosed with early-onset CLD by age 5. Of children in 2011/2012-2016/2017 with CLD, 55.8% did not achieve a good level of development, compared with 35.3% without CLD (adjusted relative risk: 1.40, 95% CI 1.34 to 1.46). Standardised total point scores were 0.69 lower (95% CI 0.58 to 0.81) in 2007/2008-2010/2011 and 0.41 lower (95% CI 0.36 to 0.46) in 2011/2012-2016/2017. Children with CLD performed worse than those without CLD in all areas of development, with the strongest effect sizes in the physical development domain. Larger effects were observed among girls, those with more severe disease and those from less deprived areas. CONCLUSIONS:Children with early-onset CLD face greater cognitive risk than their peers affected by liver transplantation hospital stays. Further exploration of longitudinal educational outcomes and their relationship with specific liver disease-related factors is needed.

OBJECTIVE:To summarise current evidence and expert perspectives on the management of paediatric portal hypertension, primarily focusing on portal hypertensive varices and gastrointestinal bleeding in children, as discussed during the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) monothematic conference meeting on portal hypertension. METHODS:In 2024, an EPSGHAN 3-day monothematic conference on paediatric portal hypertension was held in Dublin (Ireland), gathering international experts in portal hypertension. The second part of the meeting focused on clinical algorithms for acute variceal bleeding, minimally invasive radiological treatments, surgical shunts, and indications for liver transplantation. Additional sessions examined methodological constraints affecting paediatric clinical trials, supported by case-based discussions and expert panel debates. RESULTS:Faculty outlined updated approaches to emergency management for upper gastrointestinal bleeding, including stabilisation, pharmacotherapy and endoscopy treatment. Minimally invasive radiological procedures and surgical treatments were reviewed. Sessions highlighted indications for transplantation and management of post-transplant portal vein thrombosis. Presentations on registries underscored their value in rare diseases. The final session detailed the statistical, ethical and logistical challenges inherent in paediatric clinical trials and specific challenges in portal hypertension trials. CONCLUSIONS:Current management strategies across medical, endoscopic, radiological and surgical fields were reviewed, recognising the scarcity of paediatric-specific evidence. Enhanced collaboration, harmonised registries, and standardised study designs were identified as vital next steps towards optimising outcomes in children with portal hypertension.

This chapter concentrates on surgically correctable and non–surgically correctable infantile disorders of the bile ducts, including biliary atresia, choledochal cyst, spontaneous perforation of the bile duct, neonatal sclerosing cholangitis, Alagille syndrome, various forms of progressive familial cholestasis, and fibrocystic liver disease, with an emphasis on their known genetic and pathogenic mechanisms as well as their management.

OBJECTIVES:The European Liver Transplant Registry (ELTR) has been collecting data on liver transplantation (LT) in Europe since 1968. The aim of this report is to outline the number, techniques utilized, indications for, and outcomes of pediatric LT (pLT) in Europe, focusing on the Year 2022 in comparison to the preceding 5 years. METHODS:Data were obtained from ELTR and Eurotransplant (ET). Summary statistics were performed. RESULTS:In 2022, 585 pLTs were performed in Europe. The annual number of pLT decreased for the third consecutive year. Living donor LT represented 34% (n = 201) of pLT. The proportion of living donation (LD) remained stable over time. The major indication for pLT in Europe is biliary atresia. Donor age is increasing overall and is associated with worse graft survival. Graft and patient survival were impacted by both types of donors and types of grafts, and were significantly worse after re-transplantation. Most graft failures (77%) and deaths (82%) occurred within the first 6 months after pLT. CONCLUSION:Annual numbers of pLT in Europe are decreasing over time. Given that the proportion of LD has remained stable, the shortage of deceased donor organs may not be the major reason for this trend, and other factors play a role. A focus on improving perioperative care is needed because the risk of graft loss and mortality is highest in the first 6 months after transplantation. New techniques like ex-situ machine perfusion may help mitigate risks with declining quality of deceased donor liver grafts.

OBJECTIVE:To examine neurodevelopment in biliary atresia (BA) and the relationship of neurodevelopment to key disease-related factors. STUDY DESIGN:In this single-center, observational study, we deployed an anonymized survey of outcomes that was completed by 107 parents of children with BA who were younger than age 12 years. A detailed assessment of general neurodevelopment (Mullens Scale of Early Learning and Vineland Adaptive Behavior Scale) was carried out in 50 infants younger than 5 years old, and emerging autistic traits (Autism Diagnostic Observation Schedule) were assessed in those eligible. Ninety-three age- and sex-matched infants, some with greater likelihood of neurodevelopmental conditions, were used as a reference. RESULTS:Neurodevelopmental concerns were raised by 37% of parents, and 47% of children required support from at least 1 service. In the sample of children younger than 5 years, those with BA had significantly lower adaptive and cognitive skills (ANCOVA: Vineland Adaptive Behavior Scale, F = 18.26, P < .001; Mullens Scale of Early Learning, F = 9.981, P < .001) when compared with both children with lower and greater likelihood of neurodevelopmental difficulties. A clinical or research diagnosis of autism was made in 30% of 35 children >2 years old. Early surgical intervention and faster clearance of jaundice after surgery was associated with better general neurodevelopmental outcomes (F = 2.428, P = .042) but not with the presence of emerging autistic traits. CONCLUSIONS:High levels of neurodevelopmental difficulties in children with BA reveal a need for greater awareness and enhanced surveillance. That early identification and treatment of BA is linked to better general neurodevelopmental outcome and encourages proactive management. However, the novel observation that BA is associated with autistic traits unrelated to disease management will need further investigation to establish clinical relevance and optimize clinical pathways.

Autoimmune hepatitis (AIH) in children presents significant diagnostic and therapeutic challenges requiring a multidisciplinary and evidence-based approach. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN) convened a consensus meeting on February 23, 2025, bringing together national and international experts to address key clinical and research questions. The deliberations spanned epidemiology, clinical presentation, diagnosis including autoantibodies, immunoglobulin G (IgG), histology and diagnostic scores, therapeutic strategies, management of difficult-to-treat AIH, long-term monitoring, and special scenarios, such as seronegative AIH (SN-AIH), autoimmune sclerosing cholangitis/overlap syndromes and post-transplant complications like recurrence and de novo-AIH. Recommendations were formulated using standard GRADE system and finalized through structured consensus. These guidelines aim to standardize care, assist clinicians in decision-making, and improve outcomes in children with AIH across diverse healthcare settings.

Introduction Early-onset chronic liver disease (CLD) and its subsequent clinical progression have systemic impact. Its trajectory coincides with critical periods of brain development. In this study, we will test the hypothesis that early-onset CLD is associated with neurodevelopmental and psychiatric symptoms and delineate their neurobiological underpinnings through multimodal neuroimaging.Methods and analysis This study will recruit 100 patients with biliary atresia and 50 patients with other types of early-onset CLD, aged between 6 and 30 years, under the primary care of Paediatric Liver Services at King’s College Hospital, London, UK. Cognitive performance and autism-related behaviours will be evaluated with neurodevelopmental assessments. Participants and their parents will complete questionnaires addressing neurodevelopmental and psychiatric outcomes in everyday life, and quality of life. Multimodal neuroimaging will be conducted using electroencephalography (EEG); eye-tracking; structural, functional and diffusion MRI; and magnetic resonance spectroscopy (MRS). Clinical information will be collected from patients’ medical records and bio samples. Data of 222 neurotypical controls and 307 neurodivergent controls without CLD will be pooled from the Longitudinal European Autism Project with a similar study protocol. Neurodevelopmental and psychiatric outcomes will be compared with normative values and between groups. Associations with clinical risk factors will be explored using multivariable regression. Neuroimaging markers will be compared between groups and associations with neurodevelopmental outcomes and clinical risk factors will be tested using multivariable regression. Individual deviation from normal brain development will be quantified using Bayesian modelling and will be associated with neurodevelopmental outcomes.Ethics and dissemination This study was approved by the National Health Service Health Research Authority’s ethical committee (REC reference: 22/PR/1587). Findings from this study will be published in peer-reviewed journals, presented at national and international conferences and shared with patients and their families for widespread dissemination of the results.

BACKGROUND & AIMS:Juvenile autoimmune liver disease (JAILD) comprises autoimmune hepatitis and autoimmune sclerosing cholangitis. JAILD-predisposing genes include HLA-DR3,DR7, DR13 and haplotype A1-B8-DR3. Mechanisms leading to liver autoimmunity remain elusive, though JAILD patients have aberrated immunoregulation. We investigated the influence of HLA genes on immune cells, focusing on T-cells and frequency and function of T regulatory cells (Tregs) in JAILD patients, their first-degree-relatives (FDRs) and healthy controls (HCs). METHODS:HLA class I and II genotypes were defined by PCR and peripheral blood mononuclear cells were immunophenotyped by FACS in 82 patients, 72 FDRs, 50 HCs. Treg function was tested by inhibition of CD4posCD25neg T-cell proliferation. Links between HLA genes, Treg frequency/function, pro-inflammatory/immunoregulatory cytokines, soluble and membrane-bound programmed cell death-1 (PD-1) were investigated. RESULTS:Proportion of subjects carrying HLA DR3/DR7/DR13 was 88 %, 92 %, 64 % in patients, FDRs and HCs. Circulating Treg frequency was lower in patients and FDRs than HCs. Inhibitory capacity of Tregs was lower in patients but similar in FDRs compared to HCs. FDRs possessing HLA DR3/DR7/DR13 genes had Treg frequencies lower than those without. PD-1 posCD4pos T-cells were fewer in patients than HCs; PD-1posCD8pos T-cells were fewer in patients and FDRs than HCs. Patient plasma levels of IFN-γ were higher, and ratios of IFN-γ/IL-10 and IFN-γ/IL-2 lower than in HCs. All nine FDRs with autoimmune disorders had HLA DR3/DR7/DR13 genes and lower Treg frequency than those without autoimmune disorders and HCs. CONCLUSION:We show a link between HLA disease-predisposing genes and defective immunoregulation not only in JAILD patients, but also in their FDRs, who are prone to autoimmune disorders.

Background & Aims: The transfer journey from pediatric to adult care services of young people with rare liver diseases poses significant challenges and is an underexplored research area. This study examined the critical aspects of, and opportunities for, transfer journey management for these young people in Europe. Methods: In total, 72 individuals, representing 13 countries, participated in an omnistakeholder workshop on 17–18 March 2023. A standardized workshop methodology was used to discuss critical aspects and actions over nine focus sessions. The themes of these sessions were identified by engaging with healthcare providers, young people, and parents. Results (i.e. aspects receiving >25% of the votes) were ranked based on importance and validated by the European Reference Network of Hepatological Diseases (ERN RARE-LIVER) youth panel. Results: Our findings revealed that the critical aspects of transfer journey management predominantly revolved around the transfer itself. Most of the critical aspects and actions were related to improving communication (e.g. allocating sufficient time, 81% of votes; giving consistent information, 43%; and discussing communication preferences, 100%), relational continuity (e.g. appointing a transition person to liaison between stakeholders, 79%), and management continuity (e.g. using a transfer document, 60%). Our results also underscored the importance of peer mentorship programs (100%), informing young people about the transfer process (85%), and implementing joint consultations (93%). Conclusions: Current literature and guidelines on ‘transition’ might not fully address real-world challenges in rare liver diseases, particularly those concerning maintaining continuity of care during the actual transfer process. Future research should examine the effectiveness of strategies aimed at enhancing communication and continuity of care throughout the transfer journey, focusing on stakeholder experience. Impact and implications: This international omnistakeholder workshop explored challenges and opportunities in managing transfer journeys for young people with rare liver diseases. By emphasizing practical implications (leading to actions), it provides a benchmark for improving transfer journeys worldwide, applicable to not only rare liver diseases, but possibly also common liver or other rare diseases. Our findings underscore the fundamental importance of the transfer itself in maintaining continuity of care. The critical aspects identified center around informative, relational, and management continuity of care and have been transformed into minimal criteria.

The impact of chronic liver disease (CLD) in young people on lifestyle is poorly explored. One hundred four young people (20.51 years, male 44%), including 37% with autoimmune liver disease and 19% post-liver transplantation, completed an anonymous health questionnaire Thirty-nine per cent were considered overweight/obese. Female body mass index (BMI) was higher than male BMI (26.5 vs. 23.4, p = 0.018), and those taking steroids (n = 38) were more likely to be overweight/obese (66% vs. 31%, p = 0.03). Half of the cohort reported 'never' to drink alcohol and 19% had taken recreational drugs with 5% mentioning regular use of alcohol and recreational drugs each. Menstrual dysregulation was common including oligomenorrhoea (31%) and irregular periods (25%). The prevalence of overweight/obese status in young people with CLD is worrying, with females and those on steroid treatment most affected. Whereas alcohol consumption is less common compared to peers, the use of recreational drugs in this population warrants further attention.