Normalization of C1 Inhibitor in a Patient with Hereditary Angioedema.

Hereditary angioedema is a potentially life-threatening autosomal dominant condition, causing attacks of angioedema due to failure to regulate bradykinin. Nearly all cases of hereditary angioedema are caused by mutations in the gene encoding C1 inhibitor, SERPING1. C1 inhibitor is a multifunctional protein produced in the liver that regulates the kallikrein-kinin system at multiple points. An infant with genetically confirmed hereditary angioedema and low C1 inhibitor levels (but without previous episodes of angioedema) underwent liver transplantation for biliary atresia, an unrelated condition. Liver transplantation led to normalization of the C1 inhibitor level and function. To our knowledge, this represents the first patient to be potentially cured of hereditary angioedema.

Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause.

BACKGROUND: Since January 2022, there has been an increase in reports of cases of acute hepatitis of unknown cause in children. Although cases have been reported across multiple continents, most have been reported in the United Kingdom. Investigations are ongoing to identify the causative agent or agents. METHODS: We conducted a retrospective study involving children referred to a single pediatric liver-transplantation center in the United Kingdom between January 1 and April 11, 2022. These children were 10 years of age or younger and had hepatitis that met the case definition of the U.K. Health Security Agency for confirmed acute hepatitis that was not hepatitis A through E and did not have a metabolic, inherited or genetic, congenital, or mechanical cause, in the context of a serum aminotransferase level greater than 500 IU per liter. We reviewed medical records and documented demographic characteristics, clinical features, and results of liver biochemical, serologic, and molecular tests for hepatotropic and other viruses, as well as radiologic and clinical outcomes. The outcomes were classified as an improving condition, liver transplantation, or death. RESULTS: A total of 44 children had hepatitis that met the confirmed case definition, and most were previously healthy. The median age was 4 years (range, 1 to 7). Common presenting features were jaundice (in 93% of the children), vomiting (in 54%), and diarrhea (in 32%). Among the 30 patients who underwent molecular testing for human adenovirus, 27 (90%) were positive. Fulminant liver failure developed in 6 patients (14%), all of whom received a liver transplant. None of the patients died. All the children, including the 6 who received liver transplants, were discharged home. CONCLUSIONS: In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established.

The Outcome of A Centralization Program in Biliary atresia: 20 years and beyond.

OBJECTIVE: Biliary atresia (BA) is a rare disease and reported outcomes of surgical management, typically a Kasai portoenterostomy (KPE), vary considerably across the world. Centralization has been proposed to improve this. SUMMARY BACKGROUND DATA: A national centralization programme was started in Jan. 1999, involving 3 English units with co-located liver transplant facilities. As the program has now reached the 20-year point, the main aim was to update outcome statistics and identify trends. METHODS: Prospective registry and database. The main measures of outcome were (i) time to KPE, (ii) Clearance of Jaundice (CoJ), defined as reaching a bilirubin value of <20µmol/L (≈1.5 mg/dL), and (iii) actuarial native liver survival (NLS) and overall survival (OS). Data are quoted as median (IQR) and non-parametric statistical comparison used with P<0.05 regarded as significant. RESULTS: 867 infants were born with BA and managed between January 1999 and December 2019. Death occurred without intervention (n=10, 1.1%) or were subject to primary transplant (n=26, 3.0%); leaving 831 (95.9%) infants who underwent KPE at median age of 51 (IQR 39-64) days. Age at KPE reduced over the period (P=0.0001) becoming 48(35-57) days in the last 5-year era. CoJ was achieved in 505/831 (60.6%), also increasing over the period (P=0.002). 42 (5.0%) died post-KPE and 384 were transplanted, leaving 405 alive with their native livers at last follow-up. Of the 412 children transplanted, there were 23 (5.6%) deaths, leaving 387 alive. 5-year and 10-year native liver survival were 51.3% (95% CI 54.8-47.8) and 46.5% (95% CI 50.1 - 42.9) and overall survival were 91.5% (95% CI 93.2 - 89.4) and 90.5% (95% CI 92.3 - 88.2%) respectively. CONCLUSIONS: There have been continued improvements in efficiency over the period of centralization with a significant reduction in time to KPE and improved CoJ following KPE. Overall survival in this disease remains >90%.

Biliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.

BACKGROUND & AIMS: Biliary atresia (BA) is poorly understood and leads to liver transplantation (LT), with the requirement for and associated risks of lifelong immunosuppression, in most children. We performed a genome-wide association study (GWAS) to determine the genetic basis of BA. METHODS: We performed a GWAS in 811 European BA cases treated with LT in US, Canadian and UK centers, and 4,654 genetically matched controls. Whole-genome sequencing of 100 cases evaluated synthetic association with rare variants. Functional studies included whole liver transcriptome analysis of 64 BA cases and perturbations in experimental models. RESULTS: A GWAS of common single nucleotide polymorphisms (SNPs), i.e. allele frequencies >1%, identified intronic SNPs rs6446628 in AFAP1 with genome-wide significance (p = 3.93E-8) and rs34599046 in TUSC3 at sub-threshold genome-wide significance (p = 1.34E-7), both supported by credible peaks of neighboring SNPs. Like other previously reported BA-associated genes, AFAP1 and TUSC3 are ciliogenesis and planar polarity effectors (CPLANE). In gene-set-based GWAS, BA was associated with 6,005 SNPs in 102 CPLANE genes (p = 5.84E-15). Compared with non-CPLANE genes, more CPLANE genes harbored rare variants (allele frequency <1%) that were assigned Human Phenotype Ontology terms related to hepatobiliary anomalies by predictive algorithms, 87% vs. 40%, p <0.0001. Rare variants were present in multiple genes distinct from those with BA-associated common variants in most BA cases. AFAP1 and TUSC3 knockdown blocked ciliogenesis in mouse tracheal cells. Inhibition of ciliogenesis caused biliary dysgenesis in zebrafish. AFAP1 and TUSC3 were expressed in fetal liver organoids, as well as fetal and BA livers, but not in normal or disease-control livers. Integrative analysis of BA-associated variants and liver transcripts revealed abnormal vasculogenesis and epithelial tube formation, explaining portal vein anomalies that co-exist with BA. CONCLUSIONS: BA is associated with polygenic susceptibility in CPLANE genes. Rare variants contribute to polygenic risk in vulnerable pathways via unique genes. IMPACT AND IMPLICATIONS: Liver transplantation is needed to cure most children born with biliary atresia, a poorly understood rare disease. Transplant immunosuppression increases the likelihood of life-threatening infections and cancers. To improve care by preventing this disease and its progression to transplantation, we examined its genetic basis. We find that this disease is associated with both common and rare mutations in highly specialized genes which maintain normal communication and movement of cells, and their organization into bile ducts and blood vessels during early development of the human embryo. Because defects in these genes also cause other birth defects, our findings could lead to preventive strategies to lower the incidence of biliary atresia and potentially other birth defects.

Reduced Presentation of Biliary Atresia During the COVID-19 Lockdown: A Population Based Observational Study.

OBJECTIVE: The aim of this study was to assess whether there has been a change in presentations of biliary atresia (BA) in England and Wales during the first and second coronavirus disease 2019 (COVID-19) lockdowns (January-June 2020 and 2021). DESIGN: This population study assessed all confirmed cases of BA, from January 2020 to December 2021 across the 3 UK pediatric liver centers originating from England and Wales. Data was then compared to the incidence of confirmed BA cases from January to December 2017, 2018, and 2019. RESULTS: During January-June 2020 and 2021, there were only 8 and 12 presenting cases of BA in England and Wales, compared to 16, 13, and 18 for the same time periods in 2017, 2018, and 2019, respectively. This difference was significant in a two-sided t test for 2020 ( P = 0.035) but not for 2021 ( P = 0.385). There was no difference in the mean days to Kasai procedure in January-June 2020 and 2021 compared to 2017-2019; however average time to Kasai after the lockdown periods was significantly higher. CONCLUSIONS: There was a significant reduction in the presenting cases of BA during the first COVID-19 lockdown, with an increased time for BA referrals after the pandemic lockdowns were lifted in England and Wales.

Addressing extreme size mismatch in pediatric intestinal transplantation: Outcomes of intestinal length reduction.

BACKGROUND: Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy. METHODS: A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR. RESULTS: Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar. CONCLUSION: LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts.

Cigarette smoking as a risk factor for ischaemic stroke in young South Asian male migrants to Qatar: The BRAINS study.

BACKGROUND: The incidence of stroke in the Middle East is high, given its relatively young population. Smoking is a well-recognized risk factor for ischaemic stroke, and its high regional prevalence may partly account for this increased stroke risk. This research aims to determine whether young male South Asian migrants in Qatar were adversely affected by stroke depending on their smoking status. METHODS: Data from the ongoing international prospective BRAINS study was analysed. Male South Asian migrants to Qatar with a history of ischaemic stroke were recruited. Multivariate regression analysis was used to estimate the effects of comorbidities, such as BMI, hypertension, diabetes, hypercholesterolemia, alcohol consumption, and ischemic heart disease, on the association of age of stroke onset and smoking status. RESULTS: We identified 778 (mean age 49.5±10.2) migrant male workers of South Asian descent with ischaemic stroke in Qatar, of which 41.3% of the sample were current smokers. Compared to non-smokers, current smokers suffered a stroke 2.03 years earlier (95%CI: 0.60-3.46, P=0.005). Multivariate regression analysis demonstrated that only current smoking status was associated with an earlier age of stroke onset (ß=2.03, SE=0.74, P=0.006). CONCLUSION: Smoking is associated with at least a two-year earlier onset of ischaemic stroke in male South Asian migrants to the Middle East. Our study has important implications for the public health management of migrants in host countries.

Long-term outcomes of pediatric liver transplantation using organ donation after circulatory death: Comparison between full and reduced grafts.

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

Acute-on-chronic liver failure: A 20-year retrospective review of a tertiary paediatric liver centre.

AIM: Acute-on-chronic liver failure (ACLF) is an acute deterioration of pre-existing chronic liver disease related to a precipitating event. We characterised paediatric ACLF at Birmingham Children's Hospital (BCH) utilising European Association of Liver Disease CLIF criteria, including prevalence, triggers and outcomes. METHODS: All BCH patients from 2000 to 2020 with CLD who underwent initial liver transplant or died on the transplant waiting list or whilst too unwell to be listed were reviewed. RESULTS: From 2000 to 2020, 24 (4%) children with ACLF were identified. Death occurred in 18 (75%). Transplant occurred in 9 (36%), 3 of which died. ACLF triggers were sepsis organism negative 11 (46%), sepsis organism positive 8 (33%) and GI bleed 5 (17%). Bilirubin at the time of transplant/death in those with ACLF who lived compared with those who died was 529 umol/L (381) versus 665 (210) (p=0.38), creatinine 138 umol/L (147) versus 67 (46) (p=0.41), PT 33 sec (14) versus (32 (15) (p = 0.72), Grade 3, 4 hepatic encephalopathy 1 (17%) versus 10 (56%) (p = 0.17), vasopressor use 1 (17%) versus 17 (94%) (p = 0.001) and ventilation 3 (50%) versus 17 (94%) (p = 0.035). CONCLUSION: Acute-on-chronic liver failure whilst infrequent has high rates of mortality. The use of vasopressors and ventilation is more frequent in those who die from ACLF.

The flexibility and convenience of using a standard orthopaedic table in peri-articular knee fractures: Allowing ligamentotaxis and improving imaging accessibility.

Tibial plateau and distal femoral fractures are common injuries presenting a significant operative challenge. Complexity of the fracture often needs multi-planar surgical access. A combined two-staged procedure is frequently suggested both in supine and prone position to address this issue. However, this will significantly increase the operative time and eventually impact the outcome, in addition to the complications associated with prone positioning. In this study we used a standard orthopaedic table to position these patients in order to grant access to the postro-medial and a postro-lateral structures while the patient stays in supine setup, at the same time, giving the flexibility to change the alignment from valgus to varus and vice versa. This facilitates fracture reduction while addressing the anatomical structure of the knee. A further advantage is the unobstructed imaging access throughout the surgical fixation. This facilitates the reduction in operative time hence leading to a better outcome in these difficult fractures. We tested this positioning technique in more than 40 patients over a 4-year period at two different centres in the United Kingdome. We found that this approach is safe, reproducible and relatively easy to set up in the two centres.

Liver Tumours in Children: The Hepatologist's View.

ABSTRACT: Diagnostic and therapeutic innovations have changed the way we now approach liver tumours in children and adolescents. Novel imaging tools, increasing awareness, and surveillance has led to early diagnosis of benign and malignant liver tumours. Multidisciplinary interventions have favourably altered the natural course in some liver tumours. The role of liver transplantation is expanding and has become fully integrated into today's therapeutic algorithms. Transarterial locoregional and ablation therapies have been successful in adults and are being explored in children to facilitate resectability and improve outcome. For the first time, North American, Japanese, and European experts have designed a global trial to optimize management of malignant liver tumours and aim to find signature molecular profiles that will translate to individualised treatment strategies.This article aims to offer an overview of recent advances in our understanding of liver tumours in children. It focuses on the paediatric hepatologist's view and their role in the multidisciplinary management of benign and malignant liver tumours.

Outcome after ex situ or ante situm liver resection with hypothermic perfusion and auto-transplantation: A single-centre experience in adult and paediatric patients.

BACKGROUND: Evolving surgical technology and medical treatment have led to an expansion of indications to enable resection of large hepatic tumours with involvement of other abdominal structures. METHODS: Twelve extended liver and abdominal resections, either ex situ with auto-transplantation of the liver remnant or ante situm with veno-venous bypass (VVBP) were performed between 2016 and 2018. We describe our preoperative assessment, compare surgical strategies and assess outcomes. RESULTS: The median age of the 10 adult patients was 50.5 years with a majority suffering from sarcoma-like tumours. The two paediatric patients were 3 and 8 years of age, both with hepatoblastoma. Two patients underwent ex situ resections with auto-transplantation of the liver remnant, and nine patients had ante situm tumour removal with the use of VVBP in four. All patients achieved a good immediate liver function. Local infection and acute kidney injury were found in two patients. One patient underwent biliary reconstruction for bile leak. Tumour recurrence was seen in seven patients (58.3%), with four lung metastases. Five patients died from tumour recurrence (41.7%) during the follow-up. CONCLUSION: Extreme liver resections should be performed in experienced centres, where surgical subspecialties are available with access to cardiovascular support. Additionally, experience in split and living-donor liver transplantation is beneficial.

What is the long-term outlook for young people following liver transplant? A single-centre retrospective analysis of physical and psychosocial outcomes.

LT is a successful treatment for end-stage liver disease. The long-term outcome of patients transplanted in childhood has not previously been widely reported. This project assessed the long-term impact of transplantation in patients surviving >15 years. Retrospective data on growth, end-organ damage and psychosocial development were collected in young people transplanted from 1985 to 2000 in a single centre. Clinical notes were reviewed, and patients interviewed at clinic follow-up. 224 patients were transplanted between 1985 and 2000. 143 recipients (63.8%) survived >15 years with a median survival of 19.52 years. The majority were well, and only 10% had abnormal graft function (biochemical/synthetic), the main cause of which was chronic hepatitis (6%). Renal dysfunction and the necessity for renal transplant were identified in 32.8%, of whom 16.7% of patients had a cGFR <70 mL/min/1.73 m2 and 6% of patients had either undergone or awaiting renal transplant. This cohort was healthier than the average age-matched UK population in terms of body mass index (9% obese), smoking and alcohol consumption. 92% of patients had completed or were in education (93/123 had completed education and 20/123 remained in school). 63.7% of patients had been transitioned into adult services, and 46.3% of these patients were employed. 67.5% were in a relationship, one patient was divorced, and 10.6% of patients had one or more children. 11 patients had symptoms that corresponded to a DSM IV diagnosis of depression. Four patients had anorexia nervosa. Developmental delay was identified in 9 out of 99 patients. The development of malignancy, including PTLD, occurred in 10/143 (7%) patients at a median time post-transplant of 2.76 years (range 0.76-9.06 years). Epstein-Barr infection was implicated in 75% of these malignancies. We conclude the long-term outcome of LT in childhood is good with 63.8% surviving into adulthood and over 60% transferring into adult services. Graft dysfunction and end organ damage are minimal. Our cohort is healthier than the general population, and the majority have completed education, sought employment and formed relationships with peers, contributing well to society.

Atypical malignancies after intestinal transplantation in children: A European single-centre experience.

BACKGROUND: Post-transplant malignancies, that is, lymphomas, are a recognized complication in intestinal transplant recipients but are mostly secondary to EBV infection. There is an increased risk for malignancies in unusual sites in intestinal transplant recipients as compared to other solid organ transplants and the general population. OBJECTIVE: To evaluate the incidence, course, and outcome of unusual malignancies in children after ITx. METHODS: Retrospective analysis of children who underwent ITx for primary digestive disorders at Birmingham Children's Hospital between January 1989 and December 2017. RESULTS: Ninety-eight intestinal transplants were performed in 90 children (49 males and 41 females) with an underlying primary digestive disorder. Median age was 2.7 years (0.6-16.2), and median weight was 14.5 kg (5.7-53.2) at the time of transplant. Within this cohort, we identified four cases of unusual malignancies at rare sites of presentation. One patient developed cerebral PTLD, two patients were diagnosed with SMT, located at the stomal orifice and in cervicothoracic paravertebral area, respectively, and the last patient developed a retroperitoneal angiosarcoma. Unfortunately, the overall patient outcome was poor in all but one child with SMT, who currently survives with cytotoxic T-cell therapy. CONCLUSION: Unusual malignancies can occur in approximately 5% of children following ITx. A high index of suspicion is required for a timely diagnosis and adequate treatment.

The surgical management for isolated scaphotrapeziotrapezoid (STT) osteoarthritis : a systematic review of the literature.

We performed a systematic review to find out the safety and efficacy of various procedures for isolated scaphotrapeziotrapezoid osteoarthritis. Eleven articles were included. The most common procedure was arthroplasty with pyrocarbon implant (28%), followed by resection of distal pole of scaphoid with proximal trapezium and trapezoid resection (18%). The other procedures included trapeziectomy with ligament reconstruction and tendon interposition (LRTI) (14%), arthroscopic resection of distal scaphoid (11%), trapezium and trapezoid resection with LRTI (10%) and arthrodesis (10%). Complications were noted in 18 (15%) patients. The most common complication (7.5%) was asymptomatic dorsal intercalated segmental instability (DISI) followed by dislocation of the pyrocarbon implant (3%). Fusion resulted in decreased range of motion and grip strength. The distal scaphoid resection was related to high rate of DISI. Although the pyrocarbon implant has a higher dislocation rate which requires revision surgery, this complication is avoidable with good surgical technique. Arthroplasty with pyrocarbon implant may be the first choice in younger patients.

Utility of a routine bench cholangiogram for ex situ split liver procedure.

BACKGROUND: Biliary complications can result in a significant morbidity for split liver graft recipients. Biliary drainage for segment 1 and 4 is highly variable and could be the source of bile leaks. Use of a bench cholangiogram (BCH) can accurately define the segmental biliary system and identify any significant biliary radicles that need retention or repair during bench preparation of split grafts. This study evaluates the clinical relevance of routine BCH in split liver transplantation (SLT). METHODS: Retrospective review of 100 BCH images performed during ex situ deceased donor SLT between January 2009 and January 2015. The radiographs were reviewed by two surgeons and the biliary anatomy was compared using Huang and Reichert classification. RESULTS: 100 BCH images were reviewed. Variant anatomy was frequently identified in the intrahepatic bile duct system, the number and drainage patterns of segment 1&4 duct was diverse. BCH results guided the line of parenchymal transection to obtain a single segment 2&3 duct in 15 cases. A surgical intervention in the form of suture ligation of significant segment 1 or 4 duct at bench preparation was performed in 6 cases. BCH images guided surgical control of post-operative bile leak in 3 patients. CONCLUSION: Bench cholangiogram is a useful tool to guide liver parenchymal transection and potentially reduce the incidence of biliary complications.

Similarities and Differences in Allocation Policies for Pediatric Liver Transplantation Across the World.

OBJECTIVES: We aimed to investigate national allocation policies for pediatric liver transplantation (LT). METHOD: A survey was prepared by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Hepatology Committee in collaboration with the North American Studies of Pediatric Liver Transplantation consortium. The survey was sent to pediatric hepatologists and transplant surgeons worldwide. National data were obtained from centrally based registries. RESULTS: Replies were obtained from 15 countries from 5 of the world continents. Overall donation rate varied between 9 and 35 per million inhabitants. The number of pediatric LTs was 4 to 9 per million inhabitants younger than 18 years for 13 of the 15 respondents. In children younger than 2 years mortality on the waiting list (WL) varied between 0 and 20%. In the same age group, there were large differences in the ratio of living donor LT to deceased donor LT and in the ratio of split liver segments to whole liver. These differences were associated with possible discrepancies in WL mortality. CONCLUSIONS: Similarities but also differences between countries were detected. The described data may be of importance when trying to reduce WL mortality in the youngest children.

Hepatopulmonary Syndrome in Children: A 20-Year Review of Presenting Symptoms, Clinical Progression, and Transplant Outcome.

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

Transjugular Intrahepatic Portosystemic Shunt Insertion for the Management of Portal Hypertension in Children.

OBJECTIVES: the aim of the study was to describe our 20-year experience with transjugular intrahepatic portosystemic shunt (TIPSS) procedures for children with resistant portal hypertension (PHTN). METHODS: Retrospective review of all children that had a TIPSS performed at Birmingham Children's Hospital from January 1, 1995 to January 1, 2015. RESULTS: Forty children underwent 42 attempted TIPSS for resistant PHTN with recurrent variceal bleeding (n = 35), refractory ascites (n = 4), and hypersplenism (n = 1). Median age at operation was 12 years (range 7 months-17 years). Thirty-four procedures were elective and 8 were emergency cases. TIPSS was established in 33 cases (79%). Median portal venous pressure reduction was 10 mmHg. Variceal bleeding ceased in 27 (96%) and ascites improved in all. Clinical improvement following TIPSS enabled 7 children to be bridged to transplantation and 7 others to become suitable for transplantation. The 1-year and 5-year survival with TIPSS was 57% and 35%, respectively. Child-Pugh score C was an independent risk factor for adverse outcome (Likelihood ratio (LR) = 8.0; 95% confidence interval (CI) 2.7 to 23.5; P = 0.001). There were 6 major complications: hepatic artery thrombosis and infarction (n = 1), hepatic artery pseudoaneurysm (n = 1), bile leak (n = 1), and hepatic encephalopathy (n = 3). Encephalopathy was resistant to medical treatment in 2 cases, necessitating staged closure in 1. Ten patients (30%) required intervention to maintain TIPSS patency. The 1-year and 5-year freedom from reintervention was 71% and 55%, respectively. CONCLUSIONS: A TIPSS is highly successful in controlling symptoms in children with resistant PHTN and facilitating liver transplantation. It is technically demanding and not without risk. Patients must be appropriately selected and counselled.