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Background As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. Methods We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. Results There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient’s recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. Conclusions Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.

Liver transplantation (LT) for patients with propionic acidemia (PA) is an emerging therapeutic option. We present a retrospective review of patients with PA who underwent LT at a tertiary liver center between 1995 and 2015. A total of 14 children were identified (8 males) with median age at initial presentation of 3 days (range, 0-77 days). Pretransplant median protein restriction was 1 g/kg/day (range, 0.63-1.75 g/kg/day), 71% required supportive feeding, and 86% had developmental delay. Frequent metabolic decompensations (MDs) were the main indication for LT with a median age at transplantation of 2.4 years (range, 0.8-7.1 years). Only 1 graft was from a living donor, and 13 were from deceased donors (4 auxiliary). The 2-year patient survival was 86%, and overall study and graft survival was 79% and 69%, respectively. Three patients died after LT: at 43 days (biliary peritonitis), 225 days (acute-on-chronic rejection with multiorgan failure), and 13.5 years (posttransplant lymphoproliferative disease). Plasma glycine and propionylcarnitine remained elevated but reduced after transplant. Of 11 survivors, 5 had at least 1 episode of acute cellular rejection, 2 sustained a metabolic stroke (with full recovery), and 3 developed mild cardiomyopathy after LT. All have liberalized protein intake, and 9 had no further MDs: median episodes before transplant, 4 (range, 1-30); and median episodes after transplant, 0 (range, 0-5). All survivors made some developmental progress after LT, and none worsened at a median follow-up of 5.8 years (range, 2-23 years). LT in PA significantly reduces the frequency of MDs, can liberalize protein intake and improve quality of life, and should continue to be considered in selected cases.

Background: Biliary atresia (BA) is the most common indicator for liver transplant (LT) in children, however, approximately 22% will reach adulthood with their native liver, and of these, half will require transplantation later in life. The aim of this study was to analyse the surgical challenges and outcomes of patients with BA undergoing LT in adulthood. Methods: Patients with BA requiring LT at the age of 16 or older in our unit between 1989 and 2020 were included. Pretransplant, perioperative variables and outcomes were analysed. Pretransplant imaging was reviewed to assess liver appearance, spontaneous visceral portosystemic shunting (SPSS), splenomegaly, splenic artery (SA) size, and aneurysms. Results: Thirty-four patients who underwent LT for BA fulfilled the inclusion criteria, at a median age of 24 years. The main indicators for LT were synthetic failure and recurrent cholangitis. In total, 57.6% had significant enlargement of the SA, 21% had multiple SA aneurysm, and SPSS was present in 72.7% of the patients. Graft and patient survival at 1, 5, and 10 years was 97.1%, 91.2%, 91.2% and 100%, 94%, 94%, respectively Conclusions: Good outcomes after LT for BA in young patients can be achieved with careful donor selection and surgery to minimise the risk of complications. Identification of anatomical variants and shunting are helpful in guiding attitude at the time of transplant.

BACKGROUND Severe HPS increases morbidity and mortality after LT in children. We reviewed the combined experience of LT for HPS in children from two LT centers in Europe and Asia. METHODS All children with "proven" HPS as per ERS Task Force criteria (detailed in manuscript) who underwent LT were categorized into M (PaO2 ≥80 mmHg), Mo (PaO2 = 60-79 mmHg), S (50-59 mmHg), and VS (PaO2

Here, we describe a case of occlusive hepatic artery thrombus in a liver procured from an 18-year-old deceased donor after circulatory death. The donor had died of multiple trauma following a road traffic collision. Occlusive thrombus was found at the hepatic artery bifurcation during back-table preparation. Consequently, the liver transplant did not proceed. We suggest careful assessment of hepatic arteries of all donor livers before transplant, particularly those from donors who are involved in deceleration injuries. Transplanting such livers may lead to primary nonfunction.

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short‐term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6‐118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124‐179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1‐, 5‐, and 10‐year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.

The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC.LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria.346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively).LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.

Introduction Postoperative diaphragmatic hernia (DH) is a rare but potentially life-threatening complication following pediatric liver transplantation (LT). In the current literature, a total of 49 such hernias have been reported in 17 case series. We present eight additional cases, three of which reoccurred after surgical correction, and review the current literature with a focus on recurrence. Materials and Methods The study sample included children ( Results For the eight children with DH, the mean age at LT was 28.0 (5–132) months. All patients with a DH received left lateral segment split grafts except one, who received a full left lobe. The mean weight at time of LT was 11.8 (6.6–34) kg. Two patients had a primary abdominal muscle closure, and six had a temporary silastic mesh closure. All eight children presented with a right posterolateral DH. The small bowel was herniated in the majority of cases. Symptoms reported included nausea, vomiting, and respiratory distress. Two patients were asymptomatic, and discovery was incidental. All patients underwent prompt primary surgical repair. Three DH hernias (37.5%) recurred despite successful surgical correction. Conclusion DH following liver transplant with technical variant grafts may be underreported and is prone to recur despite surgical correction. A better understanding of the pathophysiology and more thorough reporting may help increase awareness. Early detection and prompt surgical management are the cornerstones of a successful outcome.

Aims Survival 20-years after paediatric liver transplantation is >80%. A correlation of this success is that long-term complications are becoming more evident. The aim of this study was to evaluate the long-term medical and psychosocial outcomes of paediatric post-liver transplant patients. Methods Cohort study of paediatric liver transplant patients in a tertiary UK transplant centre, between 1985 and 2004. Patients surviving to 10-years post-transplantation with normal liver biochemistry were included. Demographic data including indications for transplantation and complication rates were collected. All children underwent protocol liver biopsy at 10-years. Electronic case notes were reviewed for long-term physical and psychosocial outcomes. Results 84 patients survived to 10 years post-transplant. Median age at transplantation was 1.3 years, with median duration of follow-up of 20.2 years. Most common indication for liver transplantation was extrahepatic biliary atresia (51.2%). Mortality rate after 10 years was 2%. The observed acute and chronic rejection rates were 33.3% and 21.4%, respectively. A significant proportion (66.7%) of children demonstrated mild graft fibrosis at 10-years, despite having normal liver biochemistry. Long-term psychosocial consequences were significant. Roughly 26% of children had emotional and behavioral problems – depression and anxiety being the commonest. Higher rates of psychosocial disorders (35.7%, p=0.59) were seen in patients who required re-transplantation. Substance abuse including smoking and heavy alcohol consumption was lower than the national average – 9.5% and 3.6% respectively. Education and employment rates were comparable to the national average – 38% and 27%, respectively. In our cohort, 31% were in transition clinics. We report 23% with chronic renal dysfunction 20-years post-transplantation, on standard immunosuppression regimens. eGFR values were calculated using cystatin-C values. Only 3 patients had a BMI of >30, with a mean BMI of 20.4 in our cohort. Conclusion Whilst survival is excellent at 20 years, there is an emergent long-term impact of transplantation. Liver histology was abnormal in a significant proportion of our cohort despite normal liver biochemistry. Our findings demonstrate the importance of assessing physical health, specifically with regard to renal function and growth, as these children transition to adult services. The overarching impact of transplantation on the psychosocial wellbeing of survivors should form a key part of assessment post-transplantation.

Background We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum. Methods Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates. Results Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction. Conclusions The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.

Background: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and easily removable due to long retrieval wires deployed within the duodenum. Methods: 62 patients who had this stent inserted were prospectively analysed. Results: 81% of patients had long-term resolution of their stricture with a significant improvement in liver function tests. Complication rates were 15% with one patient requiring biliary reconstruction. Conclusions: This type of FCSEMS is effective and safe at resolving anastomotic strictures.

Introduction: On January 30, 2020 the World Health Organization (WHO) declared the 2019-CoV outbreak in China as a global public health emergency and subsequently, a pandemic on March 11th. It was considered that intestinal failure and intestinal transplant patients might have a higher risk of severe complications from the COVID-19 disease, multidisciplinary intestinal failure teams had to adapt their clinical approaches in order to keep this vulnerable group of patients as safe as possible during the pandemic;but data was lacking. Therefore, in order to improve our knowledge, we designed a voluntary, international survey aiming to address the impact of the COVID-19 disease in intestinal failure and transplant patients worldwide. Patient and Methods: A retrospective, observational, multicenter survey was sent to all centers registered at the Intestinal Rehabilitation and Transplant Association (IRTA). The survey contained three modules: the 1st one consisted of 14 questions about the hospital's activity during the COVID-19 pandemic. The 2nd one, contained 43 questions, was about intestinal failure patient management and outcome and the 3rd one (52 questions) focused on intestinal transplant patients. We used the Google Form platform. We aim to present the preliminary results of the first module. Statistical analysis was performed with the IBM SPSS Statistic version 25.0® program. Results: 13/42 (41%) centers responded;including centers from France, Netherlands, Italy, United States, UK, Sweden, Germany and Argentina. Only 2 centers reported moratorium on intestinal (IT) or multivisceral transplant (MVT), with a mean of 3 months (±4) [Table 1]. Since the pandemic started, 2 institutions reported 4 patients with intestinal rehabilitation or on TPN diagnosed with COVID-19 while 7 centers hospitals claimed to have had 9 patients post-IT/MTV affected by the disease. While 7 centers had their routine follow up and 'protocol biopsies' in the post-IT/MTV affected, none reported higher rates of rejection or complications. At the same time, 8 centers (77%) were affected by a mean of 15% decrease in referrals for new evaluations of intestinal failure or transplantation (compared to 2019) [Figure 1]. All centers adapted to utilizing telemedicine to follow up on IT/MVT patients Conclusions: Many aspects of healthcare have been impacted by the COVID-19 pandemic. The survey showed that the number of affected patients has been lower than expected, the reduced number of centers required transient moratorium of their activity, but a secondary observation was that despite the availability of telemedicine, and probably related to the lockdown, there has been a significant reduction in the referrals for evaluation of intestinal failure and transplant patients, that may have the deleterious effect of the delay of treatment in health care system.

Background Patient and graft survival 20-years after pediatric liver transplantation (pLT) are excellent. In children, attainment of normal growth, education and social adaptation to be an independent adult are equally important. This is particularly relevant for children who receive liver transplant at a young age, where infantile-onset liver disease, surgery and immunosuppression can adversely affect growth and neurodevelopment. The aim of this study was to evaluate the long-term physical and psychosocial outcomes of pLT recipients with normal graft function. We coin the term ‘meaningful survival'. Methods We performed a cross-sectional study of pLT recipients who received transplants between 1985 and 2004. A 20-year evaluation of physical health (growth, renal function), mental wellbeing and social outcomes (substance abuse, adherence, education, employment) was performed. All patients included were considered to have normal graft function. Findings Eighty-four patients met study criteria. Median age at transplantation was 1.3 years (IQR 0·7–3·3 years), with median duration of follow-up of 20.2 years (18·0–23·5). At median of 20-years, 19 patients (23%) had chronic renal dysfunction and 3 patients (4%) had a BMI of >30 (mean 20·4). Evaluation of long-term psychosocial outcomes demonstrated 22 patients (26%) with mental health disorders. Substance abuse was lower than national average. 62 patients (74%) were in education, employment or training. Overall, only 26% of our cohort achieved a composite outcome of ‘meaningful survival'. Interpretation This is the largest reported long-term study of biopsychosocial outcomes of pLT recipients with normal liver biochemistry, with follow-up upon completion of physical growth and senior school education. Importantly, despite normal liver function, many patients did not demonstrate ‘meaningful survival'. We must refocus our efforts towards better understanding the long-term outcomes of children. A ‘meaningful survival' rather than mere survival should be our goal. Funding None.

BACKGROUND This is the largest UK-based study on the effect of recipient body mass index (BMI) and its extremes (BMI

Background & AimsThe current shortage of livers for transplantation has increased the use of organs sourced from donation after circulatory death (DCD). These organs are prone to higher incidence of graft failure, but the underlying mechanisms are largely unknown. Here we aimed to find biomarkers of liver function before transplantation to better inform clinical evaluation.MethodsMatched pre- and post-transplant liver biopsies from DCD (n=24) and donation after brain death (DBD, n=70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. First, a discrimination analysis DCD vs DBD was used to parse metabolites associated to DCD. Then a data-driven approach was used to predict Immediate Graft Function (IGF). The metabolites were tested in models to predict survival.ResultsFive metabolites in the purine pathway were selected and investigated. The ratios of: adenine monophosphate (AMP), adenine, adenosine and hypoxanthine to urate, differed between DBD and DCD biopsies at pre-transplantation stage (qConclusionsAt liver pre-transplantation stage, a panel composed of purine metabolites and ALT in tissue could improve prediction of IGF and survival.Lay summaryNew liver function biomarkers could help clinicians assess livers before transplantation. Purines are small molecules that are found in healthy livers, and in this work we found that their levels changed critically in livers from cardiac death donors. Measuring them before transplantation improved the prediction of the liver’s immediate graft function.Graphic abstractHighlightsThe ratios of purine metabolites to urate differ between DCD and DBD in liver tissue at pre-transplantation.The ratios of purine metabolites to urate and ALT pre-transplantation can improve prediction of IGF after transplantation.Purine metabolites ratios to urate stratified 6-year survival outcome better than clinical data and donor class.

Background Liver transplantation for patients with Propionic Acidaemia (PA) remains a therapeutic option. Method Retrospective review of patients with PA who underwent liver transplantation at a tertiary liver centre between 1995 and 2015. Results Fourteen children were identified, 8 of whom were male, with median age at presentation 3 days (0–77). Pre-transplant median protein restriction was 1 g/kg/day (0.63–1.75). 86% had developmental delay; 71% required supportive feeding. Frequent metabolic decompensations were the main indication. Median age at transplantation was 2 years (0.8–8). Thirteen received cadaveric grafts (4 auxiliary) and 1 live-related donor. Two-year patient survival was 86% but overall study and graft survival was 79% and 69% respectively. Three died: at 43 days (biliary peritonitis), 225 days (acute on chronic rejection) and 13.5 years (post-transplant lymphoproliferative disease). Of 11 survivors, 5 had at least one episode of acute cellular rejection, 2 sustained metabolic stroke and 3 developed cardiomyopathy. Median follow-up duration was 4 years (2–22). All liberalised protein intake and 9 had no further metabolic decompensations (median episodes pre-transplant 4 (1–30) and post-transplant 0 (0–5)). All survivors made developmental progress, though delayed when compared with unaffected children. Plasma glycine and propionylcarnitine remained elevated but reduced post-transplant. Discussion Liver transplantation in PA significantly reduces frequency of metabolic decompensations, liberalises protein intake and should be considered in selected cases.

Liver transplantation remains the treatment of choice for patients with end-stage liver disease. However, allograft availability continues to be a problem, and extending the criteria for organ acceptance is key. Deceased donors after electrical accidents, as well as electricity-traumatized allografts, are not common but should be considered suitable. This study describes 2 cases of heart-beating organ donors with electrical injury to the liver. In 1 case, the electric shock was the cause of death; in the second case, the injury was caused by defibrillation at organ procurement. Both allografts had sustained sizeable electrical injury, and both resulted in excellent early posttransplant outcomes. These cases demonstrate that electrocution is not a contraindication to donation and that electricity-traumatized allografts may remain transplantable after careful assessment. Education of all staff in the management of such donors can optimize utility of such allografts.

Hepatocellular cancer (HCC) is an established indication for liver transplantation. This group is often allocated a donor after cardiac death (DCD) liver as a solution for waiting times. There are concerns that this approach may oncologically disadvantage HCC recipients. The aim of this study was to determine whether DCD transplantation was associated with poorer cancer-related survival in HCC.Study population was from a single institute (2001-2014) with an HCC listing diagnosis. Variables related to recipient, tumor, and graft were analyzed to determine association with HCC death.There were 347 recipients listed for HCC of which 91 received a DCD. Donor after cardiac death and donor after brain stem death (DBD) had equivalent 1-, 3-, and 5-year overall (P = 0.115) and cancer-specific survival (P = 0.7). On univariate analysis recipient age, sex, model for end stage liver disease, viral etiology had no bearing on the risk of HCC death. Neither did the graft variables of type (DCD vs DBD), donor age, steatosis, cold ischemic time, peak aspartate transaminase, day 5 bilirubin or international normalized ratio after transplant. Only tumor variables of alpha-fetoprotein, number, total diameter, microvascular invasion, and differentiation were predictors of HCC death. On multivariate analysis, predictors of HCC death remained tumor number (P = 0.002), total diameter of tumor(s) (P0.001), microvascular invasion (P = 0.025), and poor differentiation (P = 0.021).Donor liver quality in terms of graft type (DCD) has no influence on cancer related survival in transplant for HCC (hazards ratio, 1.143; 95% confidence interval, 0.528-2.423; P = 0.752).

The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q &lt, 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q &lt, 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.

Primary abdominal wall closure after intestinal and multivisceral transplantation may not be possible because of loss of abdominal domain and/or graft size/abdominal cavity mismatch. Traditional closure techniques for the open abdomen may not be valid in these circumstances because of severe scarring of the abdominal wall from multiple previous surgeries in this particular group of patients. We present our initial experience with the use of non-vascularized abdominal rectus muscle fascia in two patients who underwent deceased donation and living-related combined liver and small bowel transplantation, respectively, and who could not be closed primarily. The donor fascia was attached to the recipient fascia in both patients. In either case, there was not enough skin cover for closure, the wound was left open, and a negative pressure dressing was applied. In both cases, over a period of 6 months after placement of the non-vascularized abdominal rectus muscle fascia, the wound contracted, granulation tissue gradually covered the wound, and healing occurred, giving an intact abdominal wall. The abdominal rectus muscle fascia from a deceased donor can be used in a definite procedure for closure of the abdominal wall either at the time of transplant or later when a suitable rectus muscle fascia graft becomes available.

Introduction Biliary anastomotic strictures (AS) occur in around 30% of patients following liver transplantation and are treated by endoscopic dilatation and plastic stent (PS) insertion. However, AS frequently recur and patients require multiple procedures. The Kaffes stent (KS, Taewoong Medical) is a removable, covered metal stent designed to be deployed across AS. Methods To examine outcomes in patients with AS, we compared a recent cohort of patients treated using KS with a historical cohort of patients who received PS. Results The 22 patients (12 females) treated by KS had mean age 55 (range 22–69) years; 11 patients had DBD and 11 DCD grafts; mean cold ischaemia time was 9.6±3.3 hours. Four patients had failed previous treatment with PS. To date, 16 patients have had KS removed. The 69 patients (20 female) treated by PS were similar, mean age 51 (range 28–79) years; 47 patients had DBD and 22 DCD grafts; mean cold ischaemia time was 8.9±3.1 hours. AS resolved after one deployment of KS in 14 out of 16 patients (88%) compared to 26 out of 69 patients (38%) receiving their first PS (Relative Risk of persistent stricture (KS vs PS)=0.2, 95% CI 0.05–0.74; p=0.016; number to treat by KS for one benefit=2, 95% CI 1.3–4.0). There were no complications, including stent migration, after KS compared to 6 (8.4%) in the PS group (3 cholangitis, 2 pancreatitis, and 1 bleeding). All KS were removed successfully, although 1 stent needed 2 attempts because of wire migration. Following initial ERCP, PS patients required more ERCPs (mean 2.71 vs 1.13 more; p Conclusion Our data indicate that the KS is a promising Method for managing post-transplant AS because the majority of strictures are treated by deployment of a single stent at first ERCP.

Citrullinemia or ASS deficiency in its classical form presents in the neonatal period with poor feeding, hyperammonemia, encephalopathy, seizures, and if untreated can be fatal. Despite advances in medical therapy, neurocognitive outcomes remain suboptimal. LT has emerged as a potential management option. A retrospective single-center review identified 7 children with a median age of 1.1 years (range, 0.6-5.8) at referral. Five children presented clinically, and 2 were treated prospectively from birth due to positive family history. All patients received standard medical and dietary therapy prior to LT. The indications for LT were frequent metabolic decompensations in 4, elective in 2, and ALF in 1. The median age at LT was 2.4 years (range, 1.3-6.5). Five patients received 6 left lateral segment grafts, one a live unrelated donor left lateral segment as an APOLT graft, and one a cadaveric whole liver graft as APOLT. One child required retransplantation due to hepatic artery thrombosis. Graft and patient survival were 86% and 100%, respectively. Median follow-up is 3.1 years (range, 0.1-4.1), and the median age at follow-up is 5.5 years (range, 4.0-9.8). There have been no metabolic decompensations in 6 children, while 1 patient (with APOLT) developed asymptomatic hyperammonemia with no clinical or histological signs of liver injury, requiring additional medical therapy. Our medium-term experience following LT in citrullinemia is favorable, demonstrating a positive transformation of the clinical phenotype.

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n = 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n = 182) and caval replacement techniques (n = 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n = 4) or retransplant (n = 1), and the remainder (n = 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P = 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically not possible. Liver Transpl 21:914-921, 2015. © 2015 AASLD.

Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with 30% steatosis (n = 4), A-PSF had no beneficial effect. After isolation (n=4

Living-related liver transplantation (LRLT) was developed to increase the donor pool of size-matched organs for children. In the UK only one centre performed LRLT between 1993 and 2008. This study reports the clinical and histological outcomes following adult-to-paediatric LRLT at our centre.Forty-six LRLTs were reviewed. Recipients had a mean age, weight and PELD score of 2.4years (range 0.5-11years), 11.0kg (3.7-32.3kg) and 11.7 (-20.3 to 49.1) respectively. The incidence of post-transplant paediatric morbidity, abnormal liver function tests and histological abnormalities was reviewed.Patient and graft survival rates were 97.8%, 95.1% and 95.1%, and 97.8%, 92.1% and 71.7% at 1, 5 and 10years post-transplant respectively. Three children were re-transplanted at 44, 100 and 119months post-transplant. Nine children developed neuropsychological problems, 6 experienced educational difficulties, 5 developed post-transplant lymphoproliferative disorder and 5 suffered height or weight growth2 centile. Normal LFTs were found in 41.7%, 50%, 68% and 64.7% of children at median follow-up of 6, 13, 61 and 85months respectively. Liver histology showed hepatitis, acute rejection, non-specific changes, biliary pathology, vascular pathology and chronic rejection in 32.9%, 29.5%, 13.4%, 10.1%, 6% and 2% of biopsies respectively.The prevalence of paediatric morbidity and histological abnormalities emphasize the need for specialist and long-term follow-up following LRLT in children.

The following is the first report of a pediatric organ donor with caval agenesis and the subsequent use of this liver for transplantation. Caval embryology and potential implications of utilizing a donor liver with caval agenesis are reviewed.

AIM To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use. METHODS The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated. RESULTS DCD graft survival predictors were primary indication for transplant (P = 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10 h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively. CONCLUSION The DCD-RI score independently predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P < 0.001).

Primary hyperoxaluria type 1 (PH1) is an inherited metabolic disease that culminates in ESRF. Pre-emptive liver transplantation (pLTx) treats the metabolic defect and avoids the need for kidney transplantation (KTx). An institutional experience of pediatric PH1 LTx is reported and compared to the literature. Between 2004 and 2015, eight children underwent pLTx for PH1. Three underwent pLTx with a median GFR of 40 (30-46) mL/min/1.73 m(2) and five underwent sequential combined liver-kidney transplantation (cLKTx); all were on RRT at the time of cLKTx. In one case of pLTx, KTx was required eight and a half yr later. pLTx was performed in older (median 8 vs. 2 yr) and larger children (median 27 vs. 7.75 kg) that had a milder PH1 phenotype. In pediatric PH1, pLTx, ideally, should be performed before renal and extrarenal systemic oxalosis complications have occurred, and pLTx can be used "early" or "late." Early is when renal function is preserved with the aim to avoid renal replacement. However, in late (GFR < 30 mL/min/1.73 m(2) ), the aim is to stabilize renal function and delay the need for KTx. Ultimately, transplant strategy depends on PH1 phenotype, disease stage, child size, and organ availability.

The objective of this study was to identify peritransplant predictors of early graft survival and posttransplant parameters that could be used to predict early graft outcomes after pediatric liver transplantation (PLT). The response of children to liver dysfunction after liver transplantation (LT) is poor. No data have been reported for early predictors of poor graft survival, which would potentially be valuable for rescuing children at risk after LT. A retrospective cohort study of 422 PLT procedures performed from 2000 to 2010 at a single center was conducted. Multiple peritransplant variables were analyzed. Univariate and multivariate analyses using receiver operating characteristic curves were performed to identify predictors of early graft loss (ie, at 30, 60, and 90 days). The number needed to treat (NNT) was calculated when the risk factors were identified. Comparisons with the Olthoff criteria for early graft dysfunction in adults were performed. The overall 30-, 60-, and 90-day graft survival rates were 93.6%, 92.6%, and 90.7%, respectively. A recipient age of 0 to 2 or 6 to 16 years, acute liver failure, and a posttransplant day 7 serum bilirubin level > 200 μmol/L were risk factors for graft loss in the 3-strata Cox models. The product of the peak aspartate aminotransferase (AST) level, day 2 international normalized ratio (INR) value, and day 7 bilirubin level [with 30-, 60-, and 90-day areas under the receiver operating characteristic curve (AUROCs) of 0.774, 0.752, and 0.715, respectively] and a day 7 bilirubin level > 200 μmol/L (with 30-, 60-, and 90-day AUROCs of 0.754, 0.661, and 0.635, respectively) provided excellent prediction rates for early graft loss (30-days for Day-7-bilirubin level > 200) in the pediatric population (sensitivity = 72.7%, specificity = 96.6%, positive predictive value = 95.5%, negative predictive value = 78%). The NNT with early retransplantation when the day 7 bilirubin level was >200 μmol/L was 2.17 (unadjusted) or 2.76 (adjusted for graft survival). In conclusion, 2 scores-the product of the peak AST level, day 2 INR value, and day 7 bilirubin level and a posttransplant day 7 bilirubin level > 200 μmol/L-have been identified as clinically valuable tools with high accuracy for predicting early graft loss. A more aggressive attitude to considering early retransplantation in this group may further improve survival after LT.