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AIM: To describe the outcome of children with intestinal failure referred to Birmingham Children's Hospital (BCH) for consideration of intestinal transplantation (ITx), to determine factors for an adverse outcome and to analyse the impact of post-1998 strategies on survival. Subjects and METHODS: A retrospective analysis was performed of children referred for ITx assessment from January 1989 to December 2003. Children were assessed by a multidisciplinary team and categorised into: (a) stable on parenteral nutrition; (b) unsuitable for transplantation (Tx); and (c) recommended for Tx. To analyse the impact of the post-1998 strategies on survival, a comparison was made between the two eras (pre-1998 and post-1998). RESULTS: 152 children with chronic intestinal failure were identified (63M:89F, median age 10 months (range 1-170)). After assessment, 69 children were considered stable on parenteral nutrition (5-year survival 95%); 28 children were unsuitable for Tx (5-year survival 4%); and 55 children were recommended for Tx (5-year survival 35%, which includes 14 children who died waiting for size-matched organs). Twenty three ITx and nine isolated liver transplants (iLTx) were performed. In a multivariate analysis, the following factors in combination had an adverse effect on survival: the presence of a primary mucosal disorder (p = 0.007, OR ratio 3.16, 95% CI 1.37 to 7.31); absence of involvement of a nutritional care team at the referring hospital (p = 0.001, OR ratio 2.55, 95% CI 1.44 to 4.52); and a serum bilirubin>100 micromol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 micromol/l in the post-1998 era compared with 237 micromol/l in the pre-1998 era, p = 0.001) may be a contributory factor to improved survival. The strategies of combined en bloc reduced liver/small bowel transplantation and iLTx resulted in fewer deaths on the waiting list in the post-1998 era (2 deaths in post-1998 era v 12 deaths in pre-1998 era). The overall 3-year survival in the post-1998 era (69%) has improved compared with the pre-1998 era (31%; p<0.001) CONCLUSION: The changing characteristics at the time of referral, including earlier referral and innovative surgical strategies have resulted in improved long-term survival of children referred for ITx. [ABSTRACT FROM AUTHOR]

Deciding which patients would benefit from intestinal transplantation (IT) remains an ethical/clinical dilemma. New criteria* were proposed in 2015: ≥2 intensive care unit (ICU) admissions, loss of ≥3 central venous catheter (CVC) sites, and persistently elevated conjugated bilirubin (CB ≥ 75 μmol/L) despite 6 weeks of lipid modification strategies. We performed a retrospective, international, multicenter validation study of 443 children (61% male, median gestational age 34 weeks [IQR 29-37]), diagnosed with IF between 2010 and 2015. Primary outcome measure was death or IT. Sensitivity, specificity, NPV, PPV, and probability of death/transplant (OR, 95% confidence intervals) were calculated for each criterion. Median age at IF diagnosis was 0.1 years (IQR 0.03-0.14) with median follow-up of 3.8 years (IQR 2.3-5.3). Forty of 443 (9%) patients died, 53 of 443 (12%) were transplanted; 11 died posttransplant. The validated criteria had a high predictive value of death/IT; ≥2 ICU admissions (p < .0001, OR 10.2, 95% CI 4.0-25.6), persistent CB ≥ 75 μmol/L (p < .0001, OR 8.2, 95% CI 4.8-13.9). and loss of ≥3 CVC sites (p = .0003, OR 5.7, 95% CI 2.2-14.7). This large, multicenter, international study in a contemporary cohort confirms the validity of the Toronto criteria. These validated criteria should guide listing decisions in pediatric IT., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We evaluated long term outcomes in infants born between 1992 and 2002 with cholestatic liver disease (CLD) who underwent successful liver transplantation (LT). A total of 160 children with CLD were identified: 68 had developmental assessments before and after LT of whom 32 were excluded because they were followed up elsewhere; 16/36 consented to complete measures of IQ, anxiety, depression, health related quality of life (HRQoL), and a habits/employment survey. Illness severity and developmental attainment prior to LT were comparable with the 32 excluded and 20 patients who declined to take part. The IQ of young adults after LT (mean score = 91.13, range 75-108, SD 10.4) was not significantly improved compared to pre-LT scores (mean score = 85.7 range 50-111, SD 17), but was inversely correlated with stunting of growth and duration of disease before LT, highlighting the need for timely LT in CLD. HRQoL scores ranged from 22 to 99 (mean 64.5 SD 20.7), comparable to scores in other LT recipients. Five (31%) had mild-moderate depression; 5 (31%) had moderate-severe anxiety associated with reduced HRQoL ( P = 0.01 and P = 0.06, respectively); and nine had problematic fatigue which correlated with reduced HRQoL ( r 2 = 0.4 P = 0.007). Reduced medication adherence was associated with fatigue (Spearman correlation r 2 = 0.267; P = 0.09) and anxiety (Spearman correlation r 2 = 0.597; P = 0.02). Raised body mass index was also associated with reduced and health-related quality of life scores PeLTQL© ( r 2 = 0.379 P = 0.011). Fifteen (94%) were undergoing education or were employed. The long-term neuro-cognitive and psychosocial outcomes of young adults transplanted as babies is encouraging, although anxiety/depression was more common than in the healthy population. Psychosocial questionnaires help identify those young adult LT recipients who may benefit from support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beath, Taylor, Wray, Passingham, Lloyd and Kelly.)

Objectives: To assess the natural history and outcomes of children with intestinal failure in a large, multicenter, geographically diverse contemporary cohort (2010-2015) from 6 pediatric intestinal failure programs., Study Design: Retrospective analysis of a multicenter intestinal failure cohort (n = 443). Competing-risk analysis was used to obtain cumulative incidence rates for the primary outcome (enteral autonomy, transplantation, or death). The χ 2 test and Cox proportional hazard regression were used for bivariate and multivariable analyses., Results: The study cohort comprised 443 patients (61.2% male). Primary etiologies included short bowel syndrome (SBS), 84.9%; dysmotility disorder, 7.2%; and mucosal enteropathy, 7.9%. Cumulative incidences for enteral autonomy, transplantation, and death at 6 years of follow-up were 53.0%, 16.7%, and 10.5%, respectively. Enteral autonomy was associated with SBS, ≥50% of small bowel length, presence of an ileocecal valve (ICV), absence of portal hypertension, and follow-up in a non-high-volume transplantation center. The composite outcome of transplantation/death was associated with persistent advanced cholestasis and hypoalbuminemia; age <1 year at diagnosis, ICV, and intact colon were protective., Conclusions: The rates of death and transplantation in children with intestinal failure have decreased; however, the number of children achieving enteral autonomy has not changed significantly, and a larger proportion of patients remain parenteral nutrition dependent. New strategies to achieve enteral autonomy are needed to improve patient outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

In 2001, a Statement was published that described indications for intestinal transplantation in patients with intestinal failure expected to require parenteral nutrition indefinitely. Since 2001, advances in the management of intestinal failure including transplantation and patient survival, both on extended parenteral nutrition and after transplantation, have improved, leading to a reduction in the number of intestinal transplants worldwide from a peak of 270 per year in 2008 to 149 per year in 2017. These changes suggest that the original 2001 Statement requires reassessment. All patients with permanent intestinal failure should be managed by dedicated multidisciplinary intestinal rehabilitation teams. Under care of these teams, patients should be considered for intestinal transplantation in the event of progressive intestinal failure-associated liver disease, progressive loss of central vein access, and repeated life-threatening central venous catheter-associated infections requiring critical care. Additional indications for transplantation include large desmoid tumors and other intra-abdominal tumors with reasonable expectation of posttransplant cure, extensive mesenteric vein thrombosis and intestinal infarction, total intestinal aganglionosis, and nonrecoverable congenital secretory diarrhea. Quality of life typically improves after successful intestinal transplantation and may support the decision to proceed with transplantation when other indications are present. However, the requirement for life-long immunosuppression and its associated side effects preclude intestinal transplantation if motivated only by an expectation of improved quality of life. Increasing experience with intestinal transplantation and critical appraisal of transplant outcomes including graft survival and patient quality of life together with potential advances in immunosuppression can be expected to influence transplant practices in the future.

Introduction: Treatment of PTLD using immune-depleting agents such as RTX may be associated with increased risk of infections. The aim of this report was to describe the incidence of hypogammaglobulinemia and bacterial infections in children with PTLD after SOT at a single center since the introduction of RTX., Methods: A retrospective review was conducted over a study period of 2000-2016 in pediatric patients diagnosed with biopsy-proven PTLD based on the WHO histologic criteria. Hypogammaglobulinemia was defined by serum IgG <4 g/L; CPBI was defined by clinically significant infection by an identified pathogenic bacteria isolated from a normally sterile body site., Results: Twenty-eight patients were included, comprising 16 LTx and 12 ITx patients, and 17 patients received RTX therapy. Total of 31 episodes of CPBI occurred in 16 patients. Incidence of CPBI was 31.4 infections per 100 patient-years in RTX-treated patients, as compared to 8.4 infections per 100 patient-years in non-RTX-treated patients (P < 0.001). Hypogammaglobulinemia was significantly more prevalent after 6 months (P = 0.001) and 2 years (P = 0.005) in RTX-treated patients, as compared to none in the group that did not receive RTX. Hypogammaglobulinemia (P = 0.047), ITx (P = 0.027), and monomorphic PTLD (P = 0.024) were significantly associated with recurrent (≥2) CPBI and/or CPBI-related deaths within the first year post-PTLD., Conclusion: While RTX is an effective treatment for PTLD, hypogammaglobulinemia can persist for up to 2 years following RTX therapy, which may be associated with the higher cumulative rates of CPBI observed in RTX-treated patients., (© 2019 Wiley Periodicals, Inc.)

Objectives: Children with liver disease have increased risk of long-term cognitive deficits. We differentiated between the effects of chronic liver disease from that associated with transplantation by recruiting children with cholestatic liver disease (CLD) with and without transplantation., Methods: Psychometric measures and magnetic resonance spectroscopy were obtained for 3 groups of children: stable liver disease without transplantation; CLD from birth with transplantation; and individuals healthy to 18 months of age, before transplantation for acute liver failure., Results: Cognitive outcomes between children with different disease histories were significantly associated with the duration of liver disease but not the effects of transplantation, including that of immunosuppression. Lower intellectual ability was most frequently observed in the CLD group, whereas all of the acute liver failure group scored within the normal range. Myoinositol and glutamate/glutamine concentrations in cortex were significantly associated with disease duration across the cohort. Neurometabolite profiles in stable liver disease were consistent with subclinical encephalopathy. Impaired growth in early childhood was associated with later cognitive performance., Conclusion: Children with prolonged liver disease had the poorest cognitive outcomes despite successful transplantation, suggesting that prolonged cholestasis before transplantation adversely affects neurodevelopment, and reinforces the need for timely interventions.

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 (SpO 2 ; 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 O 2 requirement. Hb of ≥130 g/L on the day of LT correlated with a longer PICU stay (P value = 0.02), duration of supplementary O 2 (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 O 2 and PICU stay. We advocate screening for HPS with a combination of SpO 2 and Hb monitoring to facilitate earlier recognition, timely LT, and shortened recovery periods., (© 2018 by the American Association for the Study of Liver Diseases.)

EBV-CTL immunotherapy targets EBV antigens expressed by tumor cells in PTLD. Data on outcome of EBV-CTL in pSOT patients are limited. The aim of the study is to describe our experience with allogeneic, third-party EBV-CTL for the treatment of PTLD in pSOT patients in a single tertiary center. Retrospective review was performed of all pSOT patients who received EBV-CTL for PTLD. PTLD was diagnosed using World Health Organization histologic criteria. EBV-CTLs were derived from human leukocyte antigen-typed, EBV-seropositive third-party donors, and cryopreserved and maintained by an accredited national blood transfusion service. Ten patients received EBV-CTL for histologically proven PTLD from 1999 to 2016 following liver (n=5), combined intestinal/liver (n=4), and liver/kidney (n=1) transplantation. PTLD occurred at median age of 40 months (range: 12-144) and median post-transplant interval of 8 months (range: 2-107). Seven had monomorphic, two had polymorphic, and one had Hodgkin-type PTLD. All were of B-cell origin and EBV-positive on histology. EBV-CTL achieved an overall remission rate of 80% (8 of 10). Transient adverse effects included fever, tachycardia, and vomiting. None developed graft-versus-host disease or opportunistic infections. EBV-CTL is an effective treatment for PTLD in pSOT patients, with good remission rate and minimal toxicity., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There has been an estimated fivefold increase in the number of children receiving parenteral nutrition (PN) at home in the past 10 years with some children approaching the age when they should be referred to adult services whilst still on treatment. Models of care for moving young people onto adult providers of PN at home are not yet well developed, and transition is a potentially dangerous time for young people with complex health needs., Methods: A questionnaire to ascertain current experience and practices of transition in the context of home PN services was dispatched to 170 consultant gastroenterologists who were members of the British Association of Parenteral and Enteral Nutrition (BAPEN) and also to all 40 members of the Nutrition and IF working group of the British Society of Paediatric Gastroenterology and Nutrition (BSPGHAN). Anonymised returns were received from 12 adult and 18 paediatric centres., Results: We estimate about 50% paediatric IF centres, and the three largest adult IF centres responded to the survey. We identified 14 young adults already transitioned and 43 currently in transition. The practices and processes of transition reported were highly variable. Time taken to achieve transition ranged from under 6 months up to 2 years. The most frequent concerns to be identified were confusion around care routines and psychological problems at the time of transition (in one third of respondents)., Conclusions: We conclude that a transition pathway and service standards for adolescents on home PN should be developed, consideration should be given to checklists for practical aspects (e.g. pumps), key worker and psychology input to enhance emotional resilience of the young people and carers., (Copyright © 2016. Published by Elsevier Ltd.)

When cholestasis occurs in patients receiving total parenteral nutrition, it is the result of many pathogenic pathways converging on the hepatic acinus. The result may be a temporary rise in liver function tests. The resulting fibrosis, portal hypertension, and jaundice are hallmarks of type 3 intestinal-associated liver disease to which children are more susceptible than adults. The key to prevention is in identifying high-risk scenarios, meticulous monitoring, and personalized prescription of parenteral nutrition solutions combined with an active approach in reducing the impact of inflammatory events when they occur by prompt use of antibiotics and line locks., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

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 ((75)SeHCAT) 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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: Although most children discharged on home parenteral nutrition (HPN) will achieve enteral autonomy, some remain parenteral nutrition dependent; those who develop life-threatening complications may undergo small bowel transplantation (SBTx). The aim of this study was to investigate the relationship between social circumstances, compliance and complications., Subjects and Methods: An observational study in 2008-2012 on 64 children (34 HPN, 30 SBTx) from three units (two regional gastroenterology; one transplant). Social circumstances were assessed routinely as part of discharge planning; adherence by families to home care management was scored, and episodes of catheter-related blood stream infection and graft rejection were recorded for 2 years and related to compliance and social circumstances., Results: A quarter of families had a disadvantaged parent: non-English speaking (n=11), unable to read (n=5), physical disability (n=3), mental health problems disclosed (n=10); 20% children were cared for by a lone parent. Discharge home was delayed by social factors (n=9) and need for rehousing (n=17, 27%). 17/34 (50%) of HPN and 12/30 (40%) of transplant families were assessed as fully adherent. 10 families were assessed as non-adherent, eight were subject to child protection review and care was taken over by another family member (n=3) or foster parents (n=2). The risk of catheter-related blood stream infection was increased by parental disadvantage and age <3 years (p<0.05). Poor compliance was associated with complications in HPN and SBTx recipients., Conclusions: Children receiving complex home care may be socially isolated and measures to support improved compliance such as increased community support, social care involvement and respite care may improve outcomes.

Background and Aims: To evaluate risk of mortality in children with intestinal failure associated liver disease (IFALD) compared with other liver disease using two validated scores., Methods: Sixty-seven children listed for transplant were studied: cholestatic liver disease (CLDn23); liver disease secondary to other processes (LDsec n11); (IFALDn22), acute liver failure (ALFn11). Paediatric Hepatology Score (PHD) score and Pediatric end-stage liver disease score (PELD) were evaluated by Receiver Operating Curves (ROC), proportional hazards regression., Results: The highest PHD and PELD scores were found in ALF; the lowest in LDsec. Both scores correlated well in identifying waiting list (WL) mortality in patients with CLD and ALF, but not in those with IFALD where PELD scores were lower. Cox proportional hazard regression of time spent on the waiting list prior to death or transplant/delisting showed significant associations with PHD (P=0.006) and PELD (P=0.008). WL mortality was strongly predicted by disease group (6/8 deaths in IFALD). ROC analysis of all data showed that a PHD score greater than 15.5 had sensitivity of 87.5% and specificity of 81% for waiting list mortality (P<0.001); PELD greater than 8 had a sensitivity of 87.5% and specificity of 40%. Neither PHD nor PELD scores correlated with post-transplant mortality., Conclusion: PHD and PELD scores had the same sensitivity for identifying risk of WL mortality in all patients, but PELD failed to identify the sickest children with IFALD, lowering its specificity. The PHD score has the added advantage for European centres of being in SI units, not requiring a computer application to calculate and was simpler to use at bedside., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Intestinal transplantation is known to be associated with a high risk of early complications and mortality., Methods: We analyzed prospective data of 51 primary small bowel transplantations from December 1999 to August 2009 and identified perioperative factors that impact on early mortality (≤6 months after transplantation) after isolated intestinal (IITx; n=12) and combined liver-intestinal transplantation (CLITx group; n=39)., Results: Ten patients died during the first 6 months after transplantation, all of them in CLITx group (n=10/51, 19%). Multivariate analyses demonstrated intraoperative red blood cell transfusion greater than 70 mL/kg (P=0.019, odds ratio [OR]=13.79) and base excess 30-min after reperfusion less than -16 (P=0.001, OR=14.05), thrombocytopenia (<50,000 per dL) between day 1 and day 15 after transplantation (P=0.047, OR=5.22), and occurrence of vascular complications (P=0.003, OR=8.96) during the posttransplantation period as predictors of early mortality in CLITx group., Conclusion: Risk of mortality at 6 months after intestinal transplantation increased when the liver is included as combined graft. Strategies to reduce mortality such as refining selection for transplantation and early referral before the development of liver failure should be a priority.

Background & Aims: The demand for home parenteral nutrition (HPN) services for children has risen over the past 20 years. To plan a strategy for delivery of care at regional level, we carried out a national point prevalence survey of HPN during February 2010., Methods: Paediatric gastroenterologists in 33 hospitals known to have provided HPN services were identified from their membership of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition and participation in the British Intestinal Failure Survey (BIFS). Anonymised data were collated by the BIFS administrator and results compared with a similar study performed by the British Paediatric Surveillance Unit in 1993. Trends in underlying diagnosis were explored using the BIFS database for 2006-2009., Results: 139 children on HPN were reported; a fourfold increase since 1993; six of these were older than 16 years. The regional point prevalence of HPN varied from 1.76 to 41.4 per million, with a mean of 13.7 patients per million. Short bowel syndrome had increased from 27% to 63% of cases., Conclusions: The large overall increase in numbers of HPN patients suggests that a national strategy needs to be developed for the management of chronic IF., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Unlabelled: Surgical complications have a significant impact on morbidity and mortality following intestinal transplantation (ITx). Birmingham Children's Hospital commenced intestinal transplantation in 1993 and the following surgical strategies evolved: (a) pretransplant abdominal tissue expanders, 1998; (b) combined en-bloc reduced liver and intestinal transplantation (CRLITx), 1998; (c) staged abdominal closure, 2001; (d) preservation of graft duodenal artery, 2005., Aim: An internal audit was performed to document the surgical complications after ITx and to evaluate strategies in the management and prevention of complications., Methods: A retrospective analysis of the medical records from January 1993 to June 2007 was conducted to identify surgical complications, evaluate management strategies, and report outcome following ITx., Results: Forty-six children underwent 49 ITx (9 isolated intestinal, 39 combined liver and intestinal [CLITx], and 1 multivisceral transplant). Twenty three children had CRLITx since 1998, although there were none before 1997. The median donor: recipient weight ratio in CLITx was 2.2:1 (range, 0.67:1-6.70:1). Twenty-six children experienced 29 (59%) surgical complications: portacaval shunt thrombosis (n = 2, none alive); graft duodenal stump leakage (n = 3, 2 alive); spontaneous bowel perforation(n = 6, 2 alive); sub-acute bowel obstruction (n = 6, all alive); abdominal compartment syndrome ([ACS], n = 4, 2 alive); pancreatic leak (n = 3, 2 alive); biliary complications (n = 22, 17 alive ) failed staged abdominal closure with wound sepsis requiring skin grafting into the bowel (n = 1, alive), wound dehiscence (n = 1, alive), anastomotic leak (n = 1, alive) and intra-abdominal bleeding (n = 1,alive), primary nonfunction (n = 1, 1 died). Following the complications of ACS in children with primary abdominal closure and graft duodenal stump leaks in 2004, we modified our strategies in 2005 to include staged abdominal closure with recipient to donor weight mismatch, and preservation of the gastroduodenal artery during donor organ procurement in addition to pre transplant abdominal tissue expansion. Fifteen children with recipient and donor weight mismatch subsequently required staged closure of the abdomen and none of them developed ACS. Twelve children had gastroduodenal artery preserved and none developed graft duodenal stump leaks. Twenty-four of the 46 (52%) are alive 6 months to 10 years post transplant., Conclusion: Evolving strategies may avoid or reduce surgical complications commonly seen after intestinal transplantation and thus contribute to an improved outcome., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Graft availability remains a problem in pediatric intestinal transplantation (IT), with most children waiting being less than 10 kg weight. In November 2004, wait-listed children in the United Kingdom were prioritized nationally to receive pediatric donor organs to improve donor availability for IT. We aimed to evaluate the impact of this change on the recipient population., Methods: Data regarding pediatric donor organ availability and allocation were accessed from the National Transplant database. Recipient demographics and outcomes were recorded from the Liver Unit database. Between 2001 and 2006, there were 228 pediatric donors in the United Kingdom (nonheart-beating donors were excluded), of which 39 livers were allocated to emergency super-urgent liver candidates. A total of six isolated intestine and 21 liver-intestine transplants (15 reduced size, six full grafts) were performed in the same period., Results: Since January 2001, there has been a progressive reduction in overall pediatric organ donation. Increasing awareness about IT has resulted in a significant increase in number of small bowel organs being offered (71.8% vs. 19.5%), although this has been associated with an increase in referrals for transplantation. Despite an increase in number of IT being performed (2.6 vs. 7.7 mean transplants per year), waiting list mortality still remains high in smaller children (<10 kg weight). No mortality was observed in larger children and in candidates for isolated IT., Conclusions: The new prioritization of the national pediatric donor allocation favoring IT has resulted in an increased number of procedures, without an impact on waiting list mortality for small children.

Purpose of Review: The past decade has seen improvements in patient selection and a greater range of surgical procedures available to patients with intestinal failure, and this, combined with more effective immunosuppressive regimens, has transformed survival after intestinal transplantation (ITx). Much more is known about optimizing rehabilitation of the engrafted intestine in the first 12 months after transplant, but it is also becoming apparent that there are some long-term health issues to consider., Recent Findings: The key issues in rehabilitation of ITx are the immunogenic nature of the intestinal graft, which means a higher risk of rejection and necessitates relatively high levels of immune suppression that promotes infections, including Epstein-Barr virus-driven lymphoma, viral gastroenteritis and renal impairment; and those related to the specifics of an intestinal allograft (nutritional support, chylous ascites, growth, food allergy, fat soluble vitamin deficiencies, metabolic bone disease). In this article, recent publications about approaches for establishing nutrition and methods for monitoring the health of the ITx patient are reviewed., Summary: ITx appears to be cost-effective compared with parenteral nutrition, but ITx recipients continue to be vulnerable to infections, nutritional deficiencies and rejection over the long-term and, therefore, require support from and involvement of a multidisciplinary team for patients to become safely integrated with their local community.

Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.

Background: The aim was to develop a tool that measures patient dependency and disease severity in children with mild to severe liver disease., Methods: The initial pilot score was based on known markers of disease severity in acute and chronic liver disease. Between 1997 and 2001, the score was modified 4 times and reduced to comprise 10 key parameters: aspartate transaminase, prothrombin time, albumin, bilirubin, ascites, nutritional support, organ dysfunction, blood product support, sepsis and intravenous access. The score's face validity, internal consistency, interobserver agreement and construct validity were evaluated statistically and by the use of endpoints such as survival and transplant after 6 months., Results: The final 10 variable score was tested on 71 children admitted over two 3-month periods. The Cronbach's alpha score (a test for internal consistency) for the total score was 0.72. Serial data paralleled clinical deterioration and response to interventions. A Paediatric Hepatology Dependency score >15 had an odds ratio of 7 (P = 0.0125) for death or transplant at 6 months. The score was also found to agree with the paediatric end-stage liver disease score for the 12 patients being listed for liver transplantation (r = 0.660, P < 0.05)., Conclusion: The Paediatric Hepatology Dependency score is valid and internally consistent and is a convenient measure of dependency and disease severity in a heterogeneous group of patients with liver disease. It also allows admissions to be audited for comparison between eras and for monitoring the progress of patients while on the ward.

Background: Little data exist on immunosuppressive drug absorption in children with short bowel syndrome and intestinal failure associated liver disease (SBS-IFALD)., Aim: To evaluate the absorption of immunosuppressive medications in children with SBS-IFALD undergoing isolated liver transplantation (iLTx)., Methods: A retrospective review was performed in children with SBS-IFALD undergoing LTx and comparison made with weight, age-matched children undergoing iLTX (extra-hepatic biliary atresia (EHBA) and normal intestinal length and function)., Results: Seven children with SBS-IFALD undergoing iLTx (median residual bowel length, 60 cm, range 40-80) were compared with 15 children undergoing LTx for EHBA. SBS-IFALD children had significantly lower trough tacrolimus levels at three months (5.8 vs. 7.9 ng/mL, p<0.05) and six months (5.0 vs. 8.0 ng/mL, p<0.05), but equivalent levels at 12 months after iLTx. The median calculated dose-normalized concentrations indicated that systemic availability of tacrolimus was comparable in two groups at 3, 6, 12 months (33.1 vs. 23.3; 42.4 vs. 36; 51 vs. 52.9) despite the differences in enteral function. The incidence of acute rejection was 1/7 (SBS-IFALD) and 10/15 (EHBA) group (p = 0.06)., Conclusion: Children with SBS-IFALD demonstrated adequate absorption of oral tacrolimus without significant acute rejection rate after iLTx suggesting that modification of immunosuppression is not necessary.

Background: Small bowel transplantation (SBTx) offers an alternative to parenteral nutrition (PN) for the treatment of chronic intestinal failure in children: this study estimated its cost-effectiveness in the early phase of a U.K. program., Methods: Children assessed for SBTx were categorized as: 1) requiring SBTx following PN-related complications (n=23), 2) stable at home not requiring SBTx (n=24), and 3) terminally ill and unsuitable for SBTx (n=6). Costs were estimated from detailed resource-use data. Two comparisons were used for effectiveness: actual survival following transplantation (n=14) compared to: 1) estimated survival without transplantation using a prognostic model, and 2) the waiting list experiences of all patients listed for SBTx (n=23)., Results: Mean costs up to 30 months were pounds sterling 207,000 for those transplanted or on the waiting list, pounds sterling 159,000 for those stable on home PN, and pounds sterling 56,000 for those terminally ill. The prognostic model estimated a mean survival gain from transplantation of 0.12 years over 30 months, and suggested that transplantation was cost-saving. The second approach suggested that transplantation reduced survival by 0.24 years at an additional cost of pounds sterling 131,000., Conclusions: Firm conclusions on cost-effectiveness of SBTx are not possible given the two different estimates. The prognostic model approach (suggesting that pediatric SBTx may provide a small survival benefit at a small reduction in costs) should be less subject to bias, but the model requires external validation. Meanwhile, children at risk of fatal PN-complications should be given the opportunity to receive a SBTx only within a continuing formal assessment of the technology.

Introduction: Following intestinal transplant (SBT), the early diagnosis and treatment of rejection is a major management aim. The diagnosis of rejection is based on histology of stomal biopsies. Oral gentamycin (2.5 mg/kg) was used for selective decontamination of the digestive system. Our hypothesis was that gentamycin might be absorbed in the presence of graft dysfunction., Aim: Our goal was to assess the correlation between serum gentamycin level and the health of the intestinal graft., Subjects and Methods: Among 33 SBT performed from 1993 to 2005, serum gentamycin levels were performed once weekly or more often when there was a suspicion of rejection. All data were analyzed retrospectively., Results: Adequate trough levels were achieved for only 23 patients, six of whom had histologically proven rejection and only one did not have a raised gentamycin content. Five patients with raised levels but no rejection included two with severe intestinal ischemia and three with bowel obstruction/ileus. Four of the five patients required laparotomies., Conclusion: We concluded that in our study raised serum gentamycin levels were a good predictor of rejection or significant injury to the graft.

The highlights of The Ninth International Small Bowel Transplantation Symposium included the latest results from the Intestinal Transplant Registry (ITR), which demonstrated that the number of transplants performed annually continued to rise to 180 per year, most of which were performed in the United States, where the greatest number of home parenteral nutrition (PN) patients live (a prevalence of around 40 per million or 10,000 individuals). The three largest programs in the United States all use anti-CD25 monoclonal antibodies, but three different forms of lymphocyte depletion are employed in induction protocols: (1) humanized monoclonal anti-thymocyte globulin; (2) pretreatment of the recipient with Campath; (3) pretreatment of the small bowel allograft with anti-lymphocyte globulin. The main gain in these new approaches has been in the reduction in tacrolimus and steroid exposure. Indeed, the Pittsburgh team reduced tacrolimus to alternate-day dosing and stopped steroids altogether at 6 months in some patients, recording 100% survival in the past 2 years. The ITR demonstration of a difference in survival between adult patients who are hospitalized (40% to 60%) versus those who are still at home (80% to 100% survival) when called to transplant makes it almost unethical to delay evaluating patients for small bowel transplantation once they start experiencing complications on home PN. The input of gastroenterologists is also crucial in making recommendations about isolated liver transplantation for individuals with a potential to come off PN. Several important papers with useful prognostic clinical data with respect to selecting patients for isolated liver transplant were presented. It is evident from demographic surveys that only 2% to 5% adult patients and 5% to 15% children in large, well-resourced PN programs will be unlucky enough to develop life-threatening complications, but they must have rapid access to small bowel transplantation in this event. It is therefore important that the collaboration between gastroenterologists and the intestinal transplant teams continues. These excellent results for small bowel transplantation mean that the time is right for a large cost-effectiveness study comparing small bowel transplantation with PN.

Unlabelled: The 3-year survival after small bowel transplantation (SBTx) has improved to between 73% and 88%. Impaired venous access for parenteral nutrition can be an indication for SBTx in children with chronic intestinal failure., Aim: To report our experience in management of children with extreme end-stage venous access., Subjects: The study consisted of 6 children (all boys), median age of assessment 27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis (1), protracted diarrhea (1), and short bowel syndrome (4), of which gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All had a documented history of more than 10 central venous catheter insertions previously. All had venograms, and 1 child additionally had a magnetic resonance angiogram to evaluate venous access. Five of 6 presented with thrombosis of the superior vena cava (SVC) and/or inferior vena cava., Methods: Venous access was reestablished as follows: transhepatic venous catheters (5), direct intra-atrial catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of left subclavian vein after passage of a guide wire and then placing a catheter to reach the right atrium (1), radiological recanalization of the SVC and placement of a central venous catheter in situ (1), and direct puncture of SVC stump(1). Complications included serous pleural effusion after direct intra-atrial line insertion, which resolved after chest drain insertion (1), displacement of transhepatic catheter needing repositioning (2), and SVC stent narrowing requiring repeated balloon dilatation., Outcome: Four children with permanent intestinal failure on assessment were offered SBTx, 3 of which were transplanted and were established on full enteral nutrition; the family of 1 child declined the procedure. In the remaining 2 children in whom bowel adaptation was still a possibility, attempts were made to provide adequate central venous access as feeds and drug manipulations were undertaken. One of them received liver and SBTx nearly 3 years after presenting with end-stage central venous access, because attempts to achieve independence from parenteral nutrition had failed. The other child died immediately after a transhepatic venous catheter placement, possibly from a nutritional depletion syndrome as no physical cause of death was found. Direct intra-atrial catheters in transplanted children proved to be adequate for the management of uncomplicated transplantation, although the usual infusion protocol had to be modified considerably, and the lack of access would have been critical if massive blood transfusion had been required during the transplant procedure., Conclusion: It was possible to reestablish central venous access in all cases. However, this was time consuming and difficult to assemble a skilled team consisting of one of more: surgeon, cardiologist, interventional radiologist, and transplant anesthetist. Small bowel transplantation is easier and safer with adequate central venous access, and we advocate liaison with an SBTx center at an early stage.

Successful long term parenteral nutrition has transformed the prognosis for children with irreversible intestinal failure in the last three decades, but has also highlighted the long term complications: intestinal failure associated liver disease; recurrent catheter sepsis; and impaired venous access. Recent advances in small bowel transplantation and non-transplant surgical techniques now offer hope of sustained survival in the future without parenteral nutrition.

The liver develops from progenitor cells into a well-differentiated organ in which bile secretion can be observed by 12 weeks' gestation. Full maturity takes up to two years after birth to be achieved, and involves the normal expression of signalling pathways such as that responsible for the JAG1 genes (aberrations occur in Alagille's syndrome), amino acid transport and insulin growth factors. At birth, hepatocytes are already specialized and have two surfaces: the sinusoidal side receives and absorbs a mixture of oxygenated blood and nutrients from the portal vein; the other surface delivers bile and other products of conjugation and metabolism (including drugs) to the canalicular network which joins up to the bile ductules. There is a rapid induction of functions such as transamination, glutamyl transferase, synthesis of coagulation factors, bile production and transport as soon as the umbilical supply is interrupted. Anatomical specialization can be observed across the hepatic acinus which has three distinct zones. Zone 1 borders the portal tracts (also known as periportal hepatocytes) and is noted for hepatocyte regeneration, bile duct proliferation and gluconeogenesis. Zone 3 borders the central vein and is associated with detoxification (e.g. paracetamol), aerobic metabolism, glycolysis and hydrolysis and zone 2 is an area of mixed function between the two zones. Preterm infants are at special risk of hepatic decompensation because their immaturity results in a delay in achieving normal detoxifying and synthetic function. Hypoxia and sepsis are also frequent and serious causes of liver dysfunction in neonates. Stem cell research has produced many answers to the questions about liver development and regeneration, and genetic studies including studies of susceptibility genes may yield further insights. The possibility that fatty liver (increasingly recognized as non-alcoholic steatohepatitis or NASH) may have roots in the neonatal period is a concept which may have important long-term implications.

Combination of cyclosporine (CsA) and tacrolimus immunosuppression post-liver transplantation (LT) and the chemotherapeutic drugs used to treat hepatoblastoma (HB), are nephrotoxic. We aimed to determine the severity and duration of nephrotoxicity in children following LT for unresectable HB. We reviewed all children undergoing LT for unresectable HB at the Liver Unit, Birmingham Children's Hospital, UK, from 1991 to July 2000. Thirty-six children undergoing LT for biliary atresia, matched for age and sex, were selected as controls to compare pre- and post-LT renal function. Renal function was determined by estimation of glomerular filtration rate (eGFR) derived from plasma creatinine using Schwartz's formula. Twelve children with HB (mean age of diagnosis 33 months) who underwent LT (mean age 47 months) and 36 controls (mean age of LT 34 months) were studied. CsA was the main immunosuppressive drug used in each group. The median eGFR before, and at 3, 6, 12, 24 and 36 months after LT in HB group was significantly lower than controls (93 vs. 152, 66 vs. 79, 62 vs. 86, 66 vs. 87, 64 vs. 94, 53 vs. 90 mL/min/1.73 m2, respectively; 0.01 < p < 0.03). The reductions in the median eGFR of both the HB group and controls before and at 36 months after LT were 49 and 41%, respectively. At 36 months after LT, there was a trend for partial recovery of the eGFR in the controls but not in the HB group. Children who underwent LT for unresectable HB had renal dysfunction before transplantation that persisted for 36 months after LT.

Background/purpose: Extensive intestinal aganglionosis is rare. The diagnosis and treatment are known to be difficult and it had been considered to be fatal. The aim of this study was to review our experience with children with extensive intestinal aganglionosis., Methods: Retrospective analysis was conducted in patients referred to the intestinal transplantation unit since 1993. Presentation and outcome were analysed looking at 2 groups who had either undergone previous subtotal intestinal resection (group I) or no or limited resection (group II)., Results: Eight children were selected (3 patients in group I and 5 in group II). Group I was remarkable in that patients all were referred early in age with progressing liver failure. Parents of one patient refused to accept transplantation as treatment, and he died one month later. Two noncirrhotic patients were maintained in the parenteral nutrition programme and currently progress well with enteral feedings. The other 5 patients underwent transplant, and 4 of 5 are alive after transplantation with a mean follow-up of 22.2 months (range 0.4 to 63.6)., Conclusions: Subtotal resection of intestine at the time of diagnosis must be avoided. Conservative management with parenteral nutrition may be associated with long-term good outcome. Small bowel transplant may open new perspective in the management of patients with end-stage liver disease., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

Orthotopic liver transplantation (OLT) is effective therapy for end-stage liver disease but immunosuppression with calcineurin inhibitors (CNI) leads to significant nephrotoxicity, resulting in either a reduction of dosage to below the therapeutic level or omission of the drug altogether. Basiliximab (Bx) is a human/mouse chimeric monoclonal antibody that inhibits binding of interleukin-2 (IL-2) to IL-2 receptors and thus prevents proliferation of T cells, which is the main step in the development of acute cellular rejection. The aim of this study was to identify the role of Bx in the prevention of acute cellular rejection and in the reduction of nephrotoxicity in children post-liver transplantation. We evaluated three children (19 months, 22 months, and 11 yr of age; one male, two female) who were treated with Bx post-OLT on compassionate grounds. The indications were: nephrotoxicity in two children, requiring re-transplantation for hepatic artery thrombosis and recurrent giant cell hepatitis, respectively; and nephrotoxicity secondary to chemotherapy for hepatoblastoma in the third child. All patients received 10 mg of Bx, at OLT and on Day 4. Tacrolimus (0.15 mg/kg/day) was started at 48 h (n = 2) and cyclosporin (5 mg/kg/day) at 2 weeks (n = 1). Trough levels of tacrolimus were maintained at 5-8 ng/mL and trough levels of cyclosporin at 100-150 mg/L for the first 3 months. All patients received methylprednisolone (2 mg/kg) with azathioprine (1.5 mg/kg) (n = 2) and/or mycophenolate mofetil (20 mg/kg) (n = 1). The glomerular filtration rate (cGFR) was calculated using the Schwartz formula before and 10 weeks after transplant. Bx was found to be easy to administer and no major side-effects were reported. One child had two episodes of mild acute rejection at 5 and 9 weeks post-OLT and one developed chronic rejection requiring re-transplantation at 9 weeks post-OLT. One child did not develop rejection. The mean pretransplant cGFR was 58.1 (54.6-64.1) mL/min/m2. Within 10 weeks of transplantation, the cGFR had improved by 69% to a mean of 116 (88-157.6) mL/min/m2. To conclude, Bx was well tolerated in all children and had a renal sparing effect. It was effective in preventing early acute rejection, but the combination of Bx and low-dose CNI drugs did not prevent late acute or chronic rejection. Further studies to evaluate the appropriate levels of CNI immunosuppression with Bx are required.

Background: Endoscopic variceal band ligation (EVL) is the preferred method of treating variceal hemorrhage in adults. The need to reinsert the endoscope after reloading for each varix ligation has been a drawback. The Saeed multiband ligator allows ligation of multiple varices during a single insertion. The multibander has not been used previously in children., Methods: Twenty-eight consecutive children were referred to a pediatric liver unit because of esophageal variceal bleeding from 1998 to 2000. Endoscopic variceal band ligation was performed at initial endoscopy and repeated monthly until varices were obliterated or were too small to ligate., Results: Results are expressed as median (range). Age at EVL was 11 years (3 months to 16 years) and weight 30 kg (5.4-63 kg). Portal hypertension was caused by cirrhosis in 15 children. Endoscopic variceal band ligation was performed on 66 occasions with 4 bands applied per session. Ten children had active bleeding at initial endoscopy and all responded to EVL. Interval bleeding developed in 2 children before variceal ablation. Varices were obliterated in 26 of 28 patients after 2 sessions. During the 21-month follow-up (2 months to 3 years), six children have undergone elective liver transplantation and three have had mesoportal bypass procedures. Rebleeding developed in 2 of 26; 1 from recurrent esophageal varices that responded to repeat EVL and 1 from gastric varices. Following variceal ablation, 2-year actuarial variceal recurrence risk was 40%., Conclusions: Endoscopic variceal ligation is highly effective in obliterating esophageal varices in children. The use of a multibander device for endoscopic variceal ligation is technically feasible and safe even in small children, and its use results in more rapid ablation of esophageal varices.

Background: Neonates and small infants represent less than 5% of paediatric candidates for liver replacement. Most cases present under urgent conditions and receive grafts from large donors. Surgical techniques must be adapted for adequate graft preparation, vascular reconstruction, and abdominal closure., Methods: Technical aspects and outcome of 15 liver transplantations in infants weighing less than 5 kg performed at our unit were analysed retrospectively., Results: Liver transplantation was performed under urgent or highly urgent condition in 13 cases. Reduced or split liver grafts were used in all cases (median donor to recipient weight ratio, 9), including a monosegmental graft in 2 cases. In 10 cases, vascular reconstruction was done using a vascular conduit (5, 4, and 1 for artery, portal, and hepatic veins, respectively) and a delayed closure of the abdomen was necessary in 7 children. Postoperative complications were as follows: thrombosis of hepatic artery (n = 1) or portal vein (n = 1), gastrointestinal haemorrhage (n = 2), intraperitoneal bleeding (n = 1), biliary stricture (n = 2), septicaemia (n = 1). Two infants died of brain damage with a functioning graft. One child underwent retransplant for chronic rejection., Conclusions: Overall, survival rate is 60% (median follow-up, 34 months), which compares favourably with older patient groups when case mix is comparable.

Background: Early and accurate diagnosis of Crigler-Najjar syndrome, which causes prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment., Aim: To determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic information in the first 3 months of life., Methods: Retrospective review of patients with prolonged unconjugated hyperbilirubinaemia referred to the liver unit, Birmingham Children's Hospital, for the diagnosis of Crigler-Najjar syndrome. Bile bilirubin pigment composition was determined by high performance liquid chromatography. Initial diagnoses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and genetic studies., Results: Between 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyses. Based on these, two children were diagnosed with Crigler-Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five children whose initial diagnosis was CNS type 2 had resolution of jaundice and normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One of the initial cases of CNS type 1 responded to phenobarbitone with an 80% reduction in serum bilirubin consistent with CNS type 2. In all, the diagnoses of six cases needed to be reviewed., Conclusions: Early bile pigment analysis, performed during the first 3 months of life, often shows high levels of unconjugated bilirubin or bilirubin monoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler-Najjar syndrome.

A 4 year old child was referred for small bowel transplantation. He had superior vena cava obstruction secondary to numerous central venous line placements; alternative routes for long term central venous access were compromised by extensive venous occlusive disease. Patency for the superior vena cava was re-established with stenting, which allowed for radiological placement of another central venous line. Long term survival in infants and young children with intestinal failure is dependent on adequate central venous access for the administration of parenteral nutrition. Line sepsis and physical damage to the catheter often necessitates multiple central venous catheter placements during their early life and these children are at risk of catheter related veno-occlusive disease. Recurrent sepsis and the loss of satisfactory venous access for the administration of parenteral nutrition is life threatening and is an indication for intestinal transplantation in up to 41% of patients reported by the small bowel registry.