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Background The Covid-19 pandemic has exacerbated pre-existing inequalities and increased adversity and challenges for vulnerable and marginalised communities worldwide. In the UK, the Voluntary Community and Social Enterprise (VCSE) sector play a vital role in supporting the health and wellbeing of people who are marginalised or experiencing multiple complex needs. However, only a small number of studies have focused on the impact that Covid-19 had on the VCSE sector.Methods As part of a Health Inequalities Impact Assessment (HIIA), we conducted qualitative focus groups with staff and volunteers from five organisations to examine short, medium and longer-term impacts of COVID-19 upon the VCSE sector in Northern England. Nine online focus groups were conducted between March and July 2021.Findings: Focus group transcripts were analysed using Framework Analysis and yielded three central themes: (1) exacerbation of pre-existing inequalities, adversity and challenges for vulnerable and marginalised populations; (2) the ‘price’ of being flexible, innovative and agile for VCSE staff and volunteers; and (3) the voluntary sector as a ‘lifeline’ - organisational pride and resilience.Conclusions While the voluntary sector ‘adapted at pace’ to provide support during Covid-19 and in its continued aftermath, this resilience has potentially come at the cost of workforce and volunteer wellbeing, compounded by political obstacles and chronic shortage in funding and support. The VCSE sector has a vital role to play in the post-COVID ‘levelling up’ agenda. The expertise, capacity and resilience of VCSE organisations, and their ability to respond to COVID-19, should be celebrated, recognised and supported adequately to maintain its resilience. To not do so threatens the sector’s sustainability and risks jeopardising attempts to involve the sector in addressing the social determinants of health.

The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD).Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared.Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2 h vs. 6.2 h; p = .038). Recipients of FLG were significantly older (180 months vs. 7 months; p = .012) and waited significantly longer (168 days vs. 22 days; p = .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause.Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution.

Introduction The UK has been severely affected by the COVID-19 pandemic. The impact on the adult population has been disproportionately higher when compared to children with consequent challenges to organ donation and liver transplantation (LT). Across the three UK paediatric liver centres there has only been a very small number of patients who tested positive for COVID-19 and all made a speedy and full recovery. We report here the response during the pandemic across the 3 paediatric LT centres. Methods A series of nationally agreed policy changes affecting the liver procurement, listing and transplant process were agreed during regular meetings with LT centre directors and NHSE. Actions at a local and national level were agreed to protect and maintain the paediatric LT programmes. Data were collected from 27/03/20 until 26/11/20 and compared with same time period for the years 2016–19. Results During the study period, there was a significant reduction in the adult population in the mean number of weekly liver offers, donors and LTs compared to before the pandemic with signs of recovery between the 1st and 2nd UK lockdown periods (figure 1). More specifically the number of livers offered nationally was reduced from an average 30–40/week to only Overall, 65–80 paediatric LTs are performed annually across the UK’s 3 paediatric centres. From March-November 2020 there were 58(82%) elective and 13(18%) super urgent (acute liver failure & hepatoblastoma) paediatric LTs performed. Donor Brain Dead (DBD) and Donor Cardiac Dead (DCDC) LTs were 54(76%) and 3(4%), respectively. Living related LT (LRLT) programme was sustained comprising 20% of LTs performed. The number of paediatric LTs performed during the pandemic was comparable to those performed yearly since 2016. The number of LT per paediatric centre for King’s College Hospital (KCH), Birmingham Children’s Hospital (BCH) and Leeds Liver Unit were 40 (56%), 15(21%) and 16(23%), respectively with excellent outcome. A 15-year-old girl from KCH diagnosed with Wilson disease presented with liver failure and became COVID-19 positive whilst listed. She underwent LT soon after becoming COVID-19 negative. No perioperative mortality was reported with excellent outcome so far in all. Conclusion The current COVID-19 pandemic had a significant impact on the UK adult LT programme. The paediatric programme LT was preserved despite a decrease in organ offering and retrieval nationally plus limitations on adult intensive care resources at a regional level. Overall, paediatric LT outcome remained very good.

Background Increasing numbers of successful paediatric liver transplantation (PLT) with improved survival rates reaching 90%at 10 years resulted in more children being listed for PLT but this was not associated with matching expansion in graft pool resulting in graft shortage. Reports including our published early experience showed promising short and intermediate term outcomes from DCD grafts in children. Aim To compare long-term outcomes of full size and reduced DCD grafts in terms of incidence of complications as well as survival of both recipients and grafts. Methods This is a retrospective review of PLTs using DCD grafts. Patients were divided into those who received full or reduced grafts. Data was collected for comparison of pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters and outcomes. Laboratory markers were checked at discharge, 1- and 5-years post-transplant. Results 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 full size and 5 reduced grafts. Donors of both groups were Maastricht category III donors. Functional warm ischemia time did not show significant difference while cold ischemia time was significantly longer in reduced graft group. Recipients of full grafts were significantly older, heavier in weight and tend to wait significantly longer on transplant waiting list. The main indications for PLT were biliary atresia and Alpha-1 anti-trypsin deficiency. Recipients of reduced grafts were sicker pre-transplant. Post-transplant hospital and PICU stay were longer in the reduced group but this was not significant. Only significant laboratory difference was at 1-year post-transplant as albumen and creatinine were significantly higher in the full graft group while ALT was significantly higher in the reduced graft group. There was no significant difference between two groups in terms of long-term complications. 3 patients in each group survived more than 5 years post-transplant. one child was re-transplanted in the reduced group due to portal vein thrombosis, this patient received another DBD graft then unfortunately died due to liver failure. One child from full graft group also died from a non-graft related cause (figures 1, 2). Summary 14 PLTs from DCD grafts (9 full and 5 reduced) were identified. Recipients of full grafts were older and heavier while reduced graft recipients were sicker in the pre-transplant period. Both groups demonstrated comparable graft and patient survival as well as long-term complications rates. Conclusion Selected DCD grafts are potential source to widen the graft pool in children

Hepatopulmonary syndrome (HPS) in stable patients with cirrhosis can easily be overlooked. We report on the presenting symptoms, disease progression, and outcomes after liver transplantation (LT) in children with HPS. Twenty patients were diagnosed with HPS between 1996 and 2016. The etiologies were as follows: biliary atresia (n = 9); alpha-1-antitrypsin deficiency (n = 2); cryptogenic liver disease (n = 3); and others (n = 6). HPS presentations were as follows; dyspnea (n = 17) and pneumonia (n = 3). For diagnostic confirmation, the following techniques were used: technetium-99m-labeled macroaggregated albumin lung perfusion scan (n = 13) or contrast echocardiogram (n = 7). There were 16 patients listed for LT, with a median age at HPS diagnosis of 10 years and an average wait from listing to LT of 9 weeks. A marked rise in hemoglobin (Hb; median, 125-143.5 g/L) and modest decrease in oxygen saturation (SpO2 ; median 91% to 88% room air) were evident over this time. Patients' need for assisted ventilation (1 day), pediatric intensive care unit (PICU) stay (3 days), and total hospital stay (20 days) were similar to our general LT recipients-the key difference in the postoperative period was the duration of supplementary O2 requirement. Hb of ≥130 g/L on the day of LT correlated with a longer PICU stay (P value = 0.02), duration of supplementary O2 (P value = 0.005), and the need for the latter beyond 7 days after LT (P value = 0.01). Fifteen patients had resolution of their HPS after LT. The 5-, 10-, and 20-year survival rates were unchanged at 87.5%. None had a recurrence of HPS. In conclusion, HPS is a life-threatening complication of cirrhosis which usually develops insidiously. This combined with the often-stable nature of the liver disease leads to delays in diagnosis and listing for LT. Progressive polycythemia extends the need for supplementary O2 and PICU stay. We advocate screening for HPS with a combination of SpO2 and Hb monitoring to facilitate earlier recognition, timely LT, and shortened recovery periods.

Introduction: The COVID-19 pandemic has created challenges for centres performing solid organ transplantation especially with the limited availability of donors, including restrictions related to lockdowns. We aimed to assess the impact of the measures and steps taken to mitigate these challenges in order to continue to deliver intestinal/multivisceral transplantation (I/MVTx). Methods: All I/MVTx between March 2020 to December 2020 were included in the study. Data were collated from a prospectively maintained departmental database and are presented descriptively. Results: All potential I/MVTx recipients were suspended at the start of the pandemic and were reactivated after an eight week period of risk assessment. A total of five transplants were performed during the study period. (Table-1) All recipients and donors were COVID tested just prior to surgery and managed through a COVID clean patient pathway as per NHSBT. Discussion: Pre-operative precautions (screening of donor history, additional endotracheal swabs and recipient swabs) were in place at the time of the procedures. Clinical urgency mandated conscious decisions such as liver reduction and staged abdominal closure in two patients with intractable GI bleeding. Intra-operative risk mitigation strategies included utilisation of standard PPE, minimal personnel in theatre and minimisation of surgical pauses. The prioritisation of the procedures to experienced donor and recipient surgeons allowed for short Cold ischemia times (some recipient operations were started prior to cross clamp at the donor site). No changes were made to immunosuppression protocols. Post-operative follow up was changed to minimize recipient visits to the hospital. There were no routine follow up endoscopies and stomal biopsies were reduced to once-a-week and when clinically indicated. No routine follow up face-to-face outpatient appointments were made. Instead, parents were educated and supported through a process of daily weight and stoma output monitoring and these were directly reported to the consultant through e-mail. Conclusion: Adaptation to different challenges during the pandemic permitted restitution of the intestinal transplant pathway without any deleterious effect on outcomes. Changes in post discharge practice introduced will continue and may improve the patient care pathway.

Background Higher incidence of posttransplant lymphoproliferative disorder (PTLD) is reported in the pediatric small bowel transplant (SBTx) population, which may be associated with more aggressive disease and poorer outcome as compared to liver transplant (LTx) recipients. We aim to compare the characteristics and outcome of PTLD in pediatric SBTx against LTx patients at a single center. Methods Retrospective review of pediatric SBTx and LTx patients diagnosed with PTLD from 1989 to 2016 was conducted. Diagnosis of PTLD was biopsy-proven based on World Health Organization histologic criteria. Treatment protocol consisted of reduction of immunosuppression (RIS), rituximab (from 2000), cytotoxic T-lymphocyte (CTL) therapy (available in 1999-2004 and from 2011), and chemotherapy. Results Thirty-seven PTLD patients were included following LTx (n = 23, incidence = 2.8%) and SBTx (n = 14, incidence = 14.9%). Monomorphic PTLD made up 64% of SBTx and 43% of LTx cases. RIS alone resulted in remission in 50% of LTx patients but none of the SBTx patients (P = 0.002). Poorer overall remission (57% versus 96%, P = 0.004), 2-year (46% versus 91%, P = 0.003), and 5-year survival rates (39% versus 90%, P = 0.002) were observed in the SBTx group. Risk factors associated with mortality following PTLD were SBTx (odds ratio [OR], 12.00; 95% confidence interval [CI], 2.34-61.45; P = 0.003), monomorphic histology (OR, 10.63; 95% CI, 1.88-60.25; P = 0.008), multisite involvement (OR, 6.38; 95% CI, 1.35-30.14; P = 0.019), and tumor involvement of allograft (OR, 5.33; 95% CI, 1.14-24.90; P = 0.033). Introduction of CTL therapy was associated with improved survival. Conclusions Majority of PTLD following pediatric SBTx are of monomorphic subtype and associated with poorer outcome as compared to LTx patients. RIS is inadequate as a single strategy in managing PTLD in SBTx and prompt escalation to rituximab and CTL is recommended.

Background Small bowel transplant with or without a liver graft (SBTx ± LTx) for children with intestinal failure involves checking their immunity to a range of microorganisms, including hepatitis B virus (HBV), at the time of assessment. HBV vaccination in the United Kingdom is recommended for transplant candidates. The aim of this audit was to find out how many SBTx ± LTx candidates received HBV vaccination before transplantation and how the timing of vaccination influenced the development of immunity. Materials and methods Retrospective review of case notes and hospital microbiology database formed the basis of the study. Vaccination history and serology were available in 56 of 87 subjects who had SBTx ± LTx. Results All patients were seronegative for HBV when assessed for transplant. HBV vaccination was started before transplant in 25 children and after transplant in 31. Eight children died posttransplant before their immunity could be checked, but of the 48 survivors, 20 children developed immunity, of whom 13 (65%) received at least 1 vaccination before SBTx ± LTx ( P = .008). Lack of response to HBV vaccine was significantly associated with isolated bowel transplantation and intensification of immune suppression. Of 11 children, 5 lost hepatitis B surface antibody (HbsAb), and 28 never made HBsAb, despite repeated vaccinations. Conclusion Our study clearly shows that HBV vaccine before transplant is more effective. In line with renal failure patients, we suggest that children with chronic intestinal failure receive HBV vaccine when clinically stable, before referral for transplant. Higher-dose vaccines, accelerated schedules, and more frequent booster vaccinations are also strategies that may improve HBsAb levels after transplant.

Congenital intrahepatic arterio-portal fistulae (cIAPF) are rare, high-flow vascular malformations that usually present with portal hypertension. They almost never cause heart failure, unless there is associated congenital heart disease or the ductus venosus in patent. We present an unusual case of IAPF in an 11-day-old boy, who presented with features of cardiac failure associated with increased N-terminal pro-brain natriuretic peptide (NT pro-BNP). The IAPF arose directly from the aorta, separated from the hepatic artery and divided to separately supply both left and right portal veins. The ductus venosus was occluded. The IAPF was treated with embolization of the aorto-portal fistula, accessed through a direct percutaneous puncture of the fistula. Embolization was associated with an immediate clinical improvement and a rapid and sustained normalization of the NT pro-BNP level. A similar re-presentation was noted and treated with repeat embolization. The child is well on follow-up. To our knowledge, this is the first case of cIAPF, which was presented with cardiac failure when the ductus venosus has closed and has been treated successfully with direct, percutaneous transhepatic embolization of the fistula, twice. Serial clinical follow-up and ultrasonographical examinations have proven to be an effective strategy to detect recurrent fistulae.

The spleen should not be palpable under normal circumstances and therefore splenomegaly is an important clinical sign requiring further investigation.

Acute liver failure is due to necrosis of the liver leading to loss of liver function. The definition includes coagulopathy and encephalopathy. Other organs are often affected and there is a high mortality rate despite intensive care support. The initial clinical features are subtle with poor feeding, difficulty waking and poor temperature control, which can be difficult to detect in young infants. Initial investigations will show prolonged prothrombin time, hypoglycaemia, increased transaminases and bilirubin. A neonate with acute liver failure or liver dysfunction should be referred immediately to a tertiary paediatric liver centre for further advice, investigations and management. Many will require timely transfer for specialised care and consideration for transplantation. The most common causes are infection and metabolic disease (Tables 2.1 and 2.2) whilst liver vascular disease e.g. haemangioendotheliomas also present as an acutely ill baby with hepatomegaly, preserved liver biochemistry, heart failure and consumptive coagulopathy.

Jaundice is common in the neonate and up to 60% of babies are jaundiced. The most common cause is physiological jaundice which resolves by day 14. Continuing jaundice after 14 days (21 days in preterm infant) requires urgent investigation. Those who are found to have unconjugated jaundice (indirect hyperbilirubinemia) should be investigated for hypothyroidism, urinary tract infection and haemolysis.

A baby girl was born at 34+5 weeks gestation, weighing 2.5 kg, to non-consanguineous Caucasian parents. Antenatally her mother had prolonged rupture of membrane and Group B Streptococcus on vaginal swab. Her mother received antibiotics during labour. After delivery, the infant had a dose of vitamin K. Two hours later, she was commenced on benzylpenicillin and gentamicin for neonatal sepsis as she was found to be hypotensive. Femoral pulses were present. She received 10 ml/kg fluid bolus and was admitted to neonatal intensive care unit. Two hours later, she became jaundice. Bilirubin level was above the exchange transfusion threshold. Phototherapy was started. Direct Coombs test was negative. At 13 hours of age, she was hypotensive again, with temperature of 38°C. She was bleeding more than usual from her umbilical vessels when lines were inserted. Dopamine was commenced. Cranial ultrasound was unremarkable. Echocardiography showed a small patent ductus arteriosus. Clotting results were deranged, hence, she received further doses of vitamin K, fresh frozen plasma and cryoprecipitate. Albumin was 14 g/L, but liver enzyme levels were normal. She was hypoglycaemic and thrombocytopenic. Her urine output was poor. Creatinine was 169micromol/L and sodium 125 mmol/L. Aciclovir and fluconazole were added. Due to ongoing hypotension, adrenaline, noradrenaline and hydrocortisone were commenced. She was transferred to the liver centre paediatric intensive care unit. She was intubated and ventilated after platelet transfusion. Ultrasound abdomen showed slight heterogeneity of the liver parenchyma. Acute liver failure workup was sent. She was started on vasopressin for ongoing hypotension, 20% dextrose infusion, furosemide infusion, with ongoing need for clotting products. Antibiotics were rationalised to cefotaxime, metronidazole, aciclovir and ambisome. While she was about to have MRI abdomen, she developed pulmonary haemorrhage, requiring tranexemic acid and recombinant Factor VIIa. MRI abdomen was abandoned. Lip biopsy revealed deposition of stainable iron in the salivary gland epithelium, confirming the diagnosis of neonatal haemochromatosis. Liver transplant was considered but was clinically too unstable. She was not suitable for haemofiltration due to ongoing bleeding concerns. Exchange transfusion and intravenous immunoglobulins had minimal effect on her clinical condition. Intensive care was withdrawn and she passed away.

Biliary atresia is a rare disease of infancy with an estimated incidence in Europe of 1 in 15,000–19,000. The disease onset is confined to the neonatal period, and there is no equivalent liver disease outside of this period. It affects all races and ethnic groups, although black mothers are 2.5 times more likely to have a baby with biliary atresia than other ethnic groups. The pathogenesis of biliary atresia is unknown; and research to further understand the underlying mechanisms of its development is disadvantaged by the rarity of disease and lack of correlation between human and animal models. A remarkable medical achievement has been the Kasai portoenterostomy surgical procedure, which along with liver transplantation (when necessary) has increased survival into adulthood with a good quality of life.

Sensors of the innate immune system that detect intracellular nucleic acids must be regulated to prevent inappropriate activation by endogenous DNA and RNA. The exonuclease Trex1 regulates the DNA-sensing pathway by metabolizing potential DNA ligands that trigger it. However, an analogous mechanism for regulating the RIG-I-like receptors (RLRs) that detect RNA remains unknown. We found here that the SKIV2L RNA exosome potently limited the activation of RLRs. The unfolded protein response (UPR), which generated endogenous RLR ligands through the cleavage of cellular RNA by the endonuclease IRE-1, triggered the production of type I interferons in cells depleted of SKIV2L. Humans with deficiency in SKIV2L had a type I interferon signature in their peripheral blood. Our findings reveal a mechanism for the intracellular metabolism of immunostimulatory RNA, with implications for specific autoimmune disorders.

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib-polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer-Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer-Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end-stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono-renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.

For many decades in Australia, enabling educators have worked to engage people in higher education while remaining on the relative periphery of higher education institutions. Recently, there has been an intensification of focus on the value of enabling education from the government policy perspective of widening access for different equity groups, and from the institution, which increasingly operates with a focus on enabling as a source of student capital. Although different, these rationales - both governmental and neo-liberal - tend to consider the education of the student as a form of investment, conceptualised in the form of a productive, manageable citizen or as a potential source of revenue.

Gelas T, Hartley J, Mirza DF, Muiesan P, Bowen C, Sharif K. Segmental ABO-incompatible liver graft from a donor after cardiac death in neonatal acute liver failure. Pediatr Transplantation 2012: 16: E53–E57. © 2011 John Wiley & Sons A/S. Abstract: Segmental liver grafts from DCD in pediatric LT have been safely used even in acute liver failure situations. Furthermore, despite the risk of antibody-mediated acute rejection, some studies have also demonstrated the safety of ABO incompatible LT in infants. The use of such grafts can be beneficial by reducing the time on the transplant waiting list but they are more susceptible to initial dysfunction and there is a lack of enthusiasm to consider their use especially for an emergency LT as a life-saving procedure. In this short article, we describe the use and successful outcome in a neonate with fulminant acute liver failure secondary to neonatal hemochromatosis who received an ABO-incompatible reduced-size DCD graft.

Biliary atresia (BA) is an obliterative cholangiopathy presenting in the newborn period that leads to biliary cirrhosis and the need for liver transplantation in infancy unless treated early with a palliative Kasai portoenterostomy. BA is the most frequent indication for liver transplantation in children, but the pathogenesis remains unknown (1). Abnormalities of primary cilia are the cause of syndromes such as autosomal recessive polycystic kidney disease, in which renal cyst formation is associated with liver disease (2). The liver disease in ciliopathies is a ductal plate malformation leading either to congenital hepatic fibrosis or hepatic cyst development (3). In 10% to 20% of cases with BA (syndromic BA), there is an association with other specific developmental defects, including a laterality abnormality (situs inversus). Laterality is determined by primary cilia, and genes affecting laterality are involved in the organisation of cilial microtubules within the embryonal central node (4). In the present study we investigated children with BA who developed renal cysts to increase our understanding of the pathological process. We evaluated the effect of liver transplantation on cyst formation, assessed the role of primary cilia using fibrocystin as a cilial marker and looked for PKHD1 mutations in this group, and finally determined the function of their motile respiratory cilia.

Introduction The terminal ileum (TI) is important for the active reabsorption of bile salts and is the site of allograft rejection; disruption of enterohepatic circulation (EHC) may give insights to inflammatory and other physiologic processes at the TI. Subjects and methods Four children aged 5 to 12 years who had received small bowel transplantation (SBTx), 3 recovering from post-transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were studied. Two of the 4 had stoma reversal. Another child (15 years) with progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver transplantation and biliary diversion, was studied. Selenium homocholic acid taurocholate scanning (75SeHCAT) capsule was given orally (n = 3) or via introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was done 4 hours later and on days 1 to 5. Results The normal 3-day bile salt retention is 30% to 70% of baseline and normal adult biological half-life, t½ is 62 ± 17 hours. The results in children with a stoma were very low (0.1% at 7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and t½ closer to the reference range (18% at 29 hours; 22% at 33 hours). The child with PFIC + biliary diversion had an initial very high gamma emission from the stoma bag suggesting excellent reabsorption of bile salts from his TI, but retention was 0.6% and t½ 9.8 hours, demonstrating efficient biliary diversion. Conclusion These results confirm children with stomas malabsorb bile acids, which can be ameliorated after stoma closure. SeHCAT demonstrated that the biliary diversion was working well and may be helpful in preoperative assessment of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation.

Advances in surgical techniques and immunosuppressive agents have led to paediatric liver transplantation being a standard treatment option for both acute and chronic liver failure with good long term outcome and quality of life. It is important to recognise the early clinical presentation and aetiology of hepatic disease so that accurate diagnosis and management may be initiated and referral to a specialist centre made. Children with liver disease should have shared care between a regional and specialist centre with timely referral for transplant assessment and further management when complications arise.

The molecular genetic diagnosis of inherited metabolic disorders is challenging. The diseases are rare, and most show locus heterogeneity. Hence, testing of the genes associated with IMDs is time consuming and often not easily available. We report a resequencing array that allows the simultaneous resequencing of up to 92 genes associated with IMDs. To validate the array, DNA samples from 51 patients with 52 different known variants (including point variants, small insertion, and deletions [indels]) in seven genes (C140RF133, GAA, NPC1, NPC2, VPS33B, WFS1, and SLC19A2) were amplified by PCR and hybridized to the array. A further patient cohort with 48 different mutations in NPCI. were analyzed blind. Out of 76 point variants, 73 were identified using automated software analysis followed by manual review. Ten insertion and deletion variants were detected in the extra tiling using mutation specific probes, with 11 heterozygous deletions and 3 heterozygous insertions. In summary, we identified 96% (95% confidence interval [CI] 89-99%) of point variants added to the array, but the pickup rate reduced to 83% (95% CI 75-89%) when insertions/deletions were included. Although the methodology has strengths and weaknesses, application of this technique could expedite diagnosis in most patients with multilocus IMDs. Hum Mutat 31:858-865,2010. (C) 2010 Wiley-Liss, Inc.