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Summary Since April 2022, over 1000 children across 35 countries have developed episodes of acute hepatitis of unknown origin. At King’s College Hospital, a total of 65 children were referred with acute hepatitis of unknown etiology, with 10 of these children presenting with acute liver dysfunction leading to acute liver failure. Multiple hypotheses have been proposed and continue to be investigated worldwide. In this review, we explore the current understanding of potential aetiologies for this outbreak. We further characterize the proposed immunological mechanisms of liver injury in these cases.

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.

BACKGROUND Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population. METHODS Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival. RESULTS Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p

Background Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross‐sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3–4 and L4–5. Methods In this cross‐sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1–16 years who required abdominal cross‐sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3–4 and L4–5 were measured in square millimetres (mm2) as the sum of left and right PMA. Age‐specific and sex‐specific tPMA percentile curves were modelled using quantile regression. Results Computed tomography images from 779 children were included. Values of tPMA at L4–5 were significantly larger than at L3–4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm2 at L3–4 and from 447 to 2704 mm2 for L4–5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm2 at L3–4 and from 498 to 3513 mm2 at L4–5. Intraclass correlation coefficients were excellent at L3–4 (0.97, 95% CI 0.94 to 0.981) and L4–5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3–4 r = 0.90; L4–5 r = 0.90) and for girls (L3–4 r = 0.87; L4–5 r = 0.87). An online application was subsequently developed to easily calculate age‐specific and sex‐specific z‐scores and percentiles. Conclusions We provide novel paediatric age‐specific and sex‐specific growth curves for tPMA at intervertebral L3–4 and L4–5 levels for children between the ages of 1‐16 years. Together with an online tool (https://ahrc-apps.shinyapps.io/sarcopenia/), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions.

Background As a result of improved outcomes, referral to pediatric liver transplant (PLT)services has gradually increased but unfortunately graft pool did not show similar expansion resulting in graft shortage. Identifying the pre-transplant predictors of patient and graft survival can help in more effective graft allocation and can be crucial in guiding medical care and re-listing decisions. Aim Identifying pre-transplant factors that can by itself or in combination predict post-transplant patient and graft survival. Methods This is a retrospective review of PLT episodes in Leeds Teaching Hospitals NHS trust from 2000 to 2020.Univariate and Multivariate analysis of pre-transplant factors were used to identify predictors of patient and graft survival. We classified aetiology of liver disease into 6 broad categories: End stage chronic liver disease (ESCLD),Acute liver failure (ALF),acute on top of ESCLD, metabolic liver disease, tumours and re-transplantation. Grafts used were divided into whole and technical variant grafts where technical variant grafts include all split and reduced grafts, technical variant grafts were further divided into grafts from cadaveric or living donors (LD). Results 276 patients in our centre received 320 LTs. ESCLD was the main indication (60.6%) followed by re-transplantation (13.7%), ALF (10.3%), tumours (8.8%), metabolic (5.3%) and acute on top of ESCLD (1.3%). Source of liver grafts were DBD donors in 271 (84.7%) transplant episodes while 49 grafts (15.3%) were from living donors. Number of grafts per patient was one graft in 276 patients (86.2%), two grafts in 39 patients (12.2%) and three grafts in 5 (1.6%) patients. Recipients who required pre-transplant mechanical ventilation were 24 (7.5%)recipients 0.44(13.8%) patients required re-transplantation. Most common cause of graft loss was hepatic artery thrombosis (HAT) in 13 re-transplants (29.6%). At the end of study, 239(86.6%) recipients survived while 37 (13.4%) died. Most common cause of death was sepsis. Univariate analysis for patient survival (table 1) showed that following variables had a significant (p Summary This study, spanning over about 20 years, represents one of the biggest UK based PLT single centre reports. Only significant factor for patient and graft survival was era of transplant with PLT after 2010 has significantly better patient and graft survival. Conclusion Building experience has substantial effect on patient and graft survival. Traditional view of worse outcomes of smaller candidates should be changed especially in high volume centres with prolonged experience.

Objective To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). Study design Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. Results Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years were followed up for a mean of 6.8 ± 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 ± 6.1 months vs 9.3 ± 19.4 months; P = .03), did not develop liver-related complications during follow-up. Conclusions Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.

Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients., Compared to cadaveric liver transplantation, live donor LT (LDLT) is challenged by ethical, medical and surgical considerations, many of which are still unresolved. The aim of this guideline is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT.

Objectives: Our objective was to test the hypothesis that children with end-stage chronic liver disease (ESCLD) are hypermetabolic when compared to healthy children, and that this hypermetabolism persists for at least 6 months after liver transplant. Methods: Seventeen patients with end-stage chronic liver disease and 14 healthy controls had their resting energy expenditure measured (mREE) by indirect calorimetry. Weight, height, and body mass index were converted to standard deviation (SD) scores. Children older than 5 years had air displacement plethysmography and patients older than 5 years also had whole body dual-energy X-ray absorptiometry with characterization of fat mass (FM), fat-free mass (FFM), and bone-free fat free (lean) mass. Results: When compared to the prediction equation 44% of the patients and 50% of the healthy controls were hypermetabolic. The younger patients (0–5 years) had a lower mREE than the healthy controls but were significantly lighter and shorter than their healthy counterparts. mREE correlated strongly for all children with age, weight, height, and FFM. There was a strong negative correlation between age and mREE/kg in both patients (rs = −0.94, P < 0.01) and controls (rs = −0.91, P < 0.01). Almost 84% of the variance in mREE was explained by age (P < 0.001). There were no significant differences between resting energy expenditure (REE)/FFM between the 2 groups. mREE/kg before liver transplant correlated with mREE/kg after transplant (Pearson r = 0.83, P < 0.01). Conclusions: REE mostly reflected the size of the child. The patients were not hypermetabolic when compared to the healthy children. The main determinant of REE/kg after transplant was REE/kg before transplant.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism with a variety of clinical and biochemical manifestations. WD should be considered in patients with unexplained liver impairment or neuropsychiatric abnormalities. Currently, there are several diagnostic parameters postulated for WD, but no single test has been specific enough. Therefore, several diagnostic algorithms that include copper parameters and other surrogate markers like alkaline phosphatase have been evaluated. Worldwide since 2001, a diagnostic scoring system has been used, and since 2012, the WD scoring system has been adopted into the diagnostic algorithm included in the European Association for the Study of the Liver (EASL) guidelines. The availability of liver transplantation is a lifesaving treatment option for patients with WD presenting with encephalopathy and liver failure, but it has a potential of misuse in severe decompensated liver disease where chelation therapy could improve the liver disease avoiding the need for liver transplantation. In this chapter, a critical appraisal will be conducted of each parameter for the diagnosis of WD, together with other proposed diagnostic parameters.

The chapter on neonatal jaundice covers the pathophysiology of jaundice with an extensive differential for unconjugated and conjugated jaundice. It includes suggested investigations and management, as well as more detailed information on idiopathic neonatal hepatitis.

The chapter on cystic fibrosis-associated liver disease discusses the pathophysiology and clinical features of this condition. In addition it covers diagnosis, including liver biopsy, transient elastography, the role of endoscopy and magnetic resonance retrograde cholangiopancreatography, and then discusses management including the role of transplantation.

The chapter on liver function tests covers the main liver function tests used in everyday practice when assessing liver dysfunction and gives an overview of their significance.

OBJECTIVES Wilson disease (WD) is a rare inborn error of copper metabolism with diverse manifestations. There has been no study of zinc (Zn), the copper's antagonist, in WD diagnosis and severity so far. Our aims were to evaluate serum Zn in WD and its correlation with the disease severity score (revised WD index). Although the ATP7B mutation analysis is highly accurate for WD diagnosis, it may not be readily available in a resource-limiting setting. We proposed a disease diagnostic score (Proposed WD diagnostic score) which incorporates serum Zn. METHODS Medical records of WD and non-WD children seen at King's College Hospital from 2005 to 2015 were reviewed for the selected parameters using the Proposed WD diagnostic score. Available serum Zn data in WD children before disease diagnosis and the calculated severity score were statistically analyzed. Diagnostic values of the Proposed WD diagnostic score were evaluated. RESULTS Serum Zn level was significantly lower in 8 WD-acute liver failure (ALF) (5.8 [4.1-8.3] μmol/L) compared to 18 WD-non-ALF (13.5 [6.1-22.2] μmol/L) and 9 ALF from indeterminate cause (9.8 [7.0-12.1] μmol/L) (P

Intestinal transplant is now considered a viable option for children with irreversible intestinal failure suffering life limiting complications of parenteral nutrition. Identifying the possible candidates and referring them early to the transplant centre allows consideration of transplantation before the clinical situation deteriorates, and ensures the establishment of communication pathways between the family, transplant centre and the patient's local team. This encourages optimal care both before and after transplantation, and has been shown to improve long-term outcome. There are different types of intestinal transplants that may be performed according to the indication. With improvements in surgical techniques, immunosuppression, early identification of rejection and good communication between professionals and families, outcomes for patients undergoing these procedures continue to improve.

The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

Cachexia is a metabolic syndrome that manifests with excessive weight loss and disproportionate muscle wasting. It is related to many different chronic diseases, such as cancer, infections, liver disease, inflammatory bowel disease, cardiac disease, chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. Cachexia is linked with poor outcome for the patients. In this article, we explore the role of the hypothalamus, liver, muscle tissue and adipose tissue in the pathogenesis of this syndrome, particularly concentrating on the role of cytokines, hormones and cell energy-controlling pathways (such as AMPK, PI3K/Akt and mTOR). We also look at possible future directions for therapeutic strategies.