Pediatric Liver Transplant Program Research Articles

Impact of donor <i>CYP3A5</i> genotype on pharmacokinetics of tacrolimus in South African paediatric liver transplant patients

Background. In the paediatric liver transplant programme in Johannesburg, South Africa (SA), tacrolimus is the calcineurin inhibitor of choice, comprising an essential component of the immunosuppression regimen. It is characterised by a narrow therapeutic index and wide interpatient variability, necessitating therapeutic drug monitoring of whole-blood concentrations. Pharmacogenetic research, although not representative of SA population groups, suggests that single-nucleotide polymorphisms within the cytochrome P450 3A5 (CYP3A5) gene contribute to the variability in tacrolimus dosing requirements. The rs776746 polymorphism, CYP3A5*3, results in a splice defect and a non-functional enzyme. Clinically, to reach the same tacrolimus concentration-to-dose ratio (CDR), expressors (CYP3A5*1/*1 and *1/*3) require a higher tacrolimus dose than non-expressors (*3/*3). Objectives. To compare the pharmacokinetics of tacrolimus in paediatric liver transplant recipients with their donors’ CYP3A5 genotypes, considering both donor and recipient characteristics. Methods. Blood samples from 46 living liver donors were collected, their genomic DNA was extracted, and their CYP3A5 genotype was established (polymerase chain reaction and restriction fragment length polymorphism analysis, validated by Sanger sequencing). The relationship of donor and recipient characteristics with the mean tacrolimus CDR was analysed using a general linear model. Non- confounding significant variables were included in a multiple regression model. Results. The study showed that all expressor donors genotyped as CYP3A5*1/*1 were of black African self-reported race and ethnicity. During the first 15 days post-transplant, we found that children who received grafts from donor CYP3A5 expressors (CYP3A5*1/*1 and *1/*3) had significantly lower mean tacrolimus CDRs compared with those who received grafts from donor CYP3A5 non-expressors (*3/*3); the recipients of CYP3A5 expressor grafts therefore require higher doses of oral tacrolimus to achieve the same therapeutic target range. In addition, graft-to-recipient weight ratio and the CYP3A5 donor genotypes were independent factors that significantly (p<0.05) affected mean tacrolimus CDRs in recipients. Conclusion. In this study, we showed that all CYP3A5*1 homozygote donors were of black African self-reported race and ethnicity, and tacrolimus CDRs in paediatric living-donor liver transplant recipients were significantly affected by donor graft size and donor CYP3A5 genotypes. Information from this study may inform the development of an Afrocentric tacrolimus precision-medicine algorithm to optimise recipient safety and graft outcomes.

Combining living and deceased donation for pediatric first isolated liver transplantation: A win-win even in countries with high deceased donor donation rates.

Split and living donor liver transplantations are both key surgical strategies for development of pediatric liver transplant programs. Often, however, teams tend to prioritize only one preferentially. In the context of a very active national split liver graft allocation program (Italy), retrospective study of 226 consecutive pediatric first isolated liver transplants performed by a single team using organs from both deceased and living donors. Clinical characterisitics and outcome were compared. In the context of a steadily slowly decreasing split graft offer, living donation activity steadily increased. Deceased and living donation accounted for 52.6% and 47.4% of transplantations, respectively. Both strategies were equally used for transplanting patients up to 30 kg of weight, while deceased donors were predominantly used for older recipients. Technical variants represented 86% of all transplants, with 183 conisting of left lateral segment grafts (76 split liver grafts and 107 left grafts from living donors). Outcome of both surgical strategies was similar, with excellent outcomes at early, mid-, and long-term. Splitting livers of deceased donors and using living donation were complementary and non-competitive strategies for developping pediatric liver transplant activity. Implementing both activities in parallell allowed to maintain stable the number of annual transplant in Italy and allowed to reach superior outcomes. This analysis provides evidence that living donation plays a role in Italy despite an existing very active "mandatory-split" national policy.

Challenges faced in establishing a pediatric liver transplant program in a lower-middle-income country with free healthcare service.

Liver transplant is the cure for children with liver failure. Sri Lanka is a lower-middle-income country with a predominant free, state health system. Pediatric liver transplant program in Sri Lanka is still in the budding state where the initial experience of the program is yet to be documented. A retrospective review was performed including the clinical characteristics of all pediatric liver transplant recipients of Colombo North Centre for Liver Diseases since the inception of the program from June 2020 to May 2023. There were 14 PLT performed in 3 years. The median recipient age and weight were 8 years (6 months-15 years) and 23.3 kg (6.4-49.2), respectively. The majority were boys (64%). All were from low-income backgrounds. Indications for LT were acute liver failure (5/14), decompensated chronic liver disease (5/14), and acute on chronic liver failure (4/14). Underlying liver diseases were Wilson disease (6/14), autoimmune liver disease (3/14), biliary atresia (2/14) and progressive familial intrahepatic cholestasis type 3 (1/14), and unknown etiology (2/14). The majority were living donor liver transplants (86%). Of the living donors, 42% (5/12) were Buddhist priests. There were three immediate deaths and two late deaths. The 3-month survival was 78%, and overall survival was 64%. Living donor transplants carried a higher success rate (92%) compared to diseased donor transplants (0%; 2/2). Initial experience of pediatric liver transplant program of Sri Lanka is promising despite being established in a free healthcare system amidst the crisis circumstances.

Examining need and capacity for the development of a pediatric liver transplantation program in Kenya.

In Africa, pediatric liver transplantation (PLT) is currently only performed in Egypt and South Africa, leaving those who require treatment in Kenya to travel abroad. The aim of this study was to determine whether sufficient capacity and need exists in Kenya to establish a safe and sustainable PLT program. A descriptive analysis of the intensive care unit (ICU) beds, surgical workforce, current hepatobiliary volume, and estimated prevalence of pediatric liver disease (PLD) was conducted across 17 hospitals in Kenya between July and September 2020. Data were collected from medical superintendents, directors of surgical departments, or nominated proxies at Kenyan Level 5 and 6 hospitals via a web-based survey. A total of 165 ICU beds were reported at 17 facilities, with 15 facilities reporting five or more beds. About 39% of general surgeons at responding hospitals performed hepatobiliary procedures, and 30% performed pediatric surgeries. Only 10% of surgeons had pediatric training. Over half (57%) of hospitals performed hepatobiliary procedures; at the maximum, 1-5 cases were performed per week including cholecystectomy to Kasai portoenterostomy and hepatectomy. Across 13 hospitals, there were an estimated 192-570 cases of PLD seen per month. The most common PLDs were hepatitis B, neonatal hepatitis, cirrhosis, and acute hepatic failure. Overall, two hospitals possessed the minimum workforce and resources to attempt PLT. In Kenya, ICU bed availability, pediatric surgical training, and hepatobiliary volume are limited. However, the high prevalence of PLD demonstrated a significant need for PLT across all Kenyan hospitals.

Examining Need and Capacity for the Development of a Pediatric Liver Transplantation Program in Kenya

Introduction: Pediatric liver transplantation (LT) in Africa is currently only performed in Egypt and South Africa, and Kenyans requiring treatment must travel abroad. The aim of this study was to determine whether sufficient capacity and need exists in Kenya to establish a safe and sustainable pediatric LT program.

Increased use of split liver grafts in adult recipients following implementation of a pediatric liver transplant program.

Split liver transplantation (SLT) is a strategy to address organ shortage, but is a technically more demanding procedure than whole graft liver transplantation (LT). We aimed to determine the outcomes following SLT in adult recipients as well as to highlight the impact that having a pediatric LT program has on SLT implementation. All SLTs conducted at a single-center from 2010 to 2019 were identified. Patient data was obtained through retrospective review of the electronic medical record. Kaplan-Meier analysis assessed primary outcomes of 1-,3-, and 5-year graft and patient survival. We identified 37 SLTs performed at our institution from 2010 to 2019. Twenty-four donated livers resulted in 21 extended right lobes and 16 left lateral segments for adults and pediatrics recipients, respectively. Eighty-one percent (30/37) of the SLTs were performed after introduction of the combined pediatric program in 2016. 13/24 donor livers were split with both grafts allocated and used at our institution and 92% occurred after introduction of the pediatric program. Graft survival rates at 1-, 3-, and 5-years were 94% in adult recipients and 100% for all time periods in pediatric recipients. Actuarial post-transplant patient survival was 100% at 1-, 3-, and 5-years in both. The introduction of a pediatric liver transplantation program resulted in more than a fourfold increase in the number of SLTs performed at our center. Increase in allocation and use of both grafts at our institution was also seen.

An Overview of Paediatric Liver Transplant in Hospital Selayang: 2002 to 2015

Introduction: Hospital Selayang started the liver transplant program in 2002. We report a total of 81 liver transplant cases until year 2015. Among these, paediatric cases constitute almost half. This report aims to review the demography and outcome of paediatric liver transplant cases. Methodology: Case notes of all paediatric patients underwent liver transplant from year 2002 to 2015 were retrospectively reviewed. Results: A total of 38 paediatric cases received liver transplantations from year 2002 to 2015. Age at transplantation ranged from 11 months to 16 years old (mean age 6 years) and weight ranged from 6.47 to 63 kilogram (mean 18kg). There were 20 males and 18 females, 20 of them were Malay, whereas Chinese and Indian were 13 and 4 respectively. Eighteen cases were living-related and 20 cases were cadaveric liver transplants. For recipient blood group, O+ is the commonest. Biliary atresia was the most common indication for liver transplant (22 cases; 58%), followed by intrahepatic cholestasis disorders (5 cases; 13%) and metabolic disease (4 cases; 10%). Post transplantation, there were 6 (16%) biliary complications, 12 (32%) vascular complications, 26 (68%) developed early onset infection, 13% had acute rejection and 2 graft failure. Out of the 38 transplants, 79% of them survive after 1 year, and 69.7% survive after 5 years. The common causes of mortality were sepsis and vascular complications. Conclusion: Despite limited resources, a successful paediatric liver transplant programme has been established in Hospital Selayang with good survival rate.

Pediatric liver transplantation activity in a high-volume program during the COVID-19 pandemic in Brazil.

BackgroundThe impact of the COVID pandemic on liver transplant (LT) programs varied among countries. Few data are available about that impact in pediatric liver transplant (PLT) programs. This study aimed at comparing the data of our program in Brazil (2019 vs. 2020).MethodsRetrospective cohort study.ResultsOne hundred and seventy‐four PLT were performed in the period (93% living donors). Patients were divided into two groups according to the LT date: pre‐COVID‐19 period (march/2019–February/2020) and COVID‐19 period (March/2020–February 2021). In the pre‐COVID‐19 period, 97 LTs were performed, and 77 LTs were performed in the COVID‐19 period. Patients in the COVID‐19 period were younger (10.9 months vs. 16 months, p 0.009), had higher PELD scores (15 vs. 14, p 0.04), more ascites (66.2 vs. 51.5%, p 0.03), and more frequently hospitalized before LT (27.3 vs. 17.5%). However, there was no difference in post‐LT complications, retransplantation nor survival rates. Six (6.2%) patients from pre‐COVID‐19 period were COVID positive at a median of 15.5 months (14–17.5), and 6 (7.8%) patients from COVID‐19 period were COVID positive at a median of 3 months (20 days–6 months) from LT. There was neither mortality nor complications in those patients. Four (33%) were hospitalized, and one had prolonged intubation. Four (33%) were asymptomatic, 4 (33%) had upper airways symptoms, and the remaining had gastrointestinal symptoms.ConclusionOverall, PLT was not affected during COVID‐19 period. Even though patients from COVID‐19 period were sicker, there was no significant impact in LT outcomes. All the recipients who tested positive for COVID had a favorable outcome.

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.

Liver Transplantation in Croatia: "David Among Goliaths".

Liver Transplantation in Croatia: "David Among Goliaths".

Genetic disease and intellectual disability as contraindications to transplant listing in the United States: A survey of heart, kidney, liver, and lung transplant programs.

Discrimination based on disability is prohibited in organ transplantation, yet studies suggest it continues in listing practices for intellectual disability and genetic diseases. It is not known if this differs between adult and pediatric programs, or by organ type. We performed an online, forced-choice survey of psychosocial listing criteria for adult and pediatric heart, kidney, liver, and lung transplant programs in the United States. Of 650 programs contacted, 343 (52.8%) submitted complete. A minority of programs had formal listing guidelines for any condition considered (Down Syndrome, Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, DiGeorge Syndrome, and Wolf Hirschhorn Syndrome; and mild [IQ<70] and severe [IQ<35] intellectual disability), although a majority had encountered most. Pediatric programs were significantly (P<.02) more lenient in the level of contraindication to listing for all genetic conditions considered except Duchenne Muscular Dystrophy, and for mild and severe intellectual disability. Level of contraindication differed significantly by organ type (heart, lung, liver, and kidney) for Duchenne Muscular dystrophy (P=<.001), Becker Muscular Dystrophy (P<.001), DiGeorge Syndrome (P<.001), Wolf-Hirschhorn syndrome (P=.0012), and severe intellectual disability (P<.001). There is significant variation among transplant programs in availability of guidelines for as well as listing practices regarding genetic diseases and intellectual disability, differing by both adult vs pediatric program, and organ type. Programs with absolute contraindications to listing for specific genetic diseases or intellectual disability should reframe their approach, ensuring individualized assessments and avoiding elimination of patients based on membership in a particular group.

Routine Postoperative Antithrombotic Therapy in Pediatric Liver Transplantation: Impact on Bleeding and Thrombotic Complications.

Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are serious causes of morbidity and mortality after pediatric liver transplantation. To reduce thrombotic complications, routine antithrombotic therapy consisting of 1 week heparin followed by 3 months acetylsalicylic acid, was implemented in our pediatric liver transplant program in 2003. This study aimed to evaluate incidences of bleeding and thrombotic complications since the implementation of routine antithrombotic therapy and to identify risk factors for these complications. This retrospective cohort study includes 200 consecutive pediatric primary liver transplantations performed between 2003 and 2016. Uni- and multivariate logistic regression analysis, Kaplan-Meier method, and Cox regression analysis were used to evaluate recipient outcome. HAT occurred in 15 (7.5%), PVT in 4 (2.0%), and venous outflow tract thrombosis in 2 (1.0%) recipients. Intraoperative vascular interventions (odds ratio [OR] 14.45 [95% confidence interval [CI] 3.75-55.67]), low recipient age (OR 0.81 [0.69-0.95]), and donor age (OR 0.96 [0.93-0.99]) were associated with posttransplant thrombosis. Clinically relevant bleeding occurred in 37%. Risk factors were high recipient age (OR 1.08 [1.02-1.15]), high Child-Pugh scores (OR 1.14 [1.02-1.28]), and intraoperative blood loss in mL/kg (OR 1.003 [1.001-1.006]). Both posttransplant thrombotic (hazard ratio [HR] 3.38 [1.36-8.45]; p = 0.009) and bleeding complications (HR 2.50 [1.19-5.24]; p = 0.015) significantly increased mortality. In 200 consecutive pediatric liver transplant recipients receiving routine postoperative antithrombotic therapy, we report low incidences of posttransplant vascular complications. Posttransplant antithrombotic therapy seems to be a valuable strategy in pediatric liver transplantation. Identified risk factors for bleeding and thrombotic complications might facilitate a more personalized approach in antithrombotic therapy.

Healthcare transition in pediatric liver transplantation: The perspectives of pediatric and adult healthcare professionals.

Transition from pediatric to adult services of young people with a liver transplant is an important priority due to increasing numbers of young people surviving into adulthood. There is increased incidence of graft loss and non-adherence following transfer to adult services. Although studies have considered the views and perceptions of young people who have undergone liver transplantation and their parents about transition, there is currently no qualitative research with healthcare professionals working in the field of liver transplantation. The aim of this study was to elicit the views of this group of stakeholders about barriers and facilitators of an effective transition process. Semi-structured interviews were carried out with 11 HCPs from pediatric and adult liver transplant programs and from a range of professional backgrounds. Interviews were transcribed verbatim and analyzed using thematic analysis. Four themes were identified: "non-adherence and psychosocial issues," "need for better psychological support," "the role of parents," and "the emotional impact of transition on healthcare professionals." Within these themes, professionals described factors which hindered or promoted an effective transition process. Screening tools which address psychological and social aspects of the lives of young people should be used in routine practice to identify patients requiring psychosocial support and to identify those at risk of non-adherence. All staff involved with transition should be trained in the use of psychosocial screening strategies. The development of a formal referral pathway so that young people can access psychological support in adult services is recommended.

Medical Contraindications to Transplant Listing in the USA: A Survey of Adult and Pediatric Heart, Kidney, Liver, and Lung Programs.

Listing practices for solid organ transplantation are variable across programs in the USA. To better characterize this variability, we performed a survey of psychosocial listing criteria for pediatric and adult heart, lung, liver, and kidney programs in the USA. In this manuscript, we report our results regarding listing practices with respect to obesity, advanced age, and HIV seropositivity. We performed an online, forced-choice survey of adult and pediatric heart, kidney, liver, and lung transplant programs in the USA. Of 650 programs contacted, 343 submitted complete responses (response rate = 52.8%). Most programs have absolute contraindications to listing for BMI > 45 (adult: 67.5%; pediatric: 88.0%) and age > 80 (adult: 55.4%; pediatric: not relevant). Only 29.5% of adult programs and 25.7% of pediatric programs consider HIV seropositivity an absolute contraindication to listing. We found that there is variation in absolute contraindications to listing in adult programs among organ types for BMI > 45 (heart 89.8%, lung 92.3%, liver 49.1%, kidney 71.9%), age > 80 (heart 83.7%, lung 76.9%, liver 68.4%, kidney 29.2%), and HIV seropositivity (heart 30.6%, lung 59.0%, kidney 16.9%, liver 28.1%). We argue that variability in listing enhances access to transplantation for potential recipients who have the ability to pursue workup at different centers by allowing different programs to have different risk thresholds. Programs should remain independent in listing practices, but because these practices differ, we recommend transparency in listing policies and informing patients of reasons for listing denial and alternative opportunities to seek listing at another program.

Use of genetic risks in pediatric organ transplantation listing decisions: A national survey.

There is a limited supply of organs for all those who need them for survival. Thus, careful decisions must be made about who is listed for transplant. Studies show that manifesting genetic disease can impact listing eligibility. What has not yet been studied is the impact genetic risks for future disease have on a patient's chance to be listed. Surveys were emailed to 163 pediatric liver, heart, and kidney transplant programs across the United States to elicit views and experiences of key clinicians regarding each program's use of genetic risks (ie, predispositions, positive predictive testing) in listing decisions. Response rate was 42%. Sixty-four percent of programs have required genetic testing for specific indications prior to listing decisions. Sixteen percent have required it without specific indications, suggesting that genetic testing may be used to screen candidates. Six percent have chosen not to list patients with secondary findings or family histories of genetic conditions. In hypothetical scenarios, programs consider cancer predispositions and adult-onset neurological conditions to be relative contraindications to listing (61%, 17%, and 8% depending on scenario), and some consider them absolute contraindications (5% and 3% depending on scenario). Only 3% of programs have formal policies for these scenarios, but all consult genetic specialists at least "sometimes" for results interpretation. Our study reveals that pediatric transplant programs are using future onset genetic risks in listing decisions. As genetic testing is increasingly adopted into pediatric medicine, further study is needed to prevent possible inappropriate use of genetic information from impacting listing eligibility.

Trends in transfusion practice over 20years in paediatric liver transplant programme.

We investigated changes to transfusion practices over time in paediatric liver transplant centre and evaluated the effect of transfusion practice to mortality. A pilot retrospective study included two cohorts each with 101 sequential paediatric LT recipients: an Early group (1994-1998) and a Recent group (2009-2013). Demographic characteristics and data on the intraoperative transfusion of red blood cells (RBC), fresh-frozen plasma (FFP), platelets and cryoprecipitate were collected. Postoperative laboratory results were also obtained, together with donor and data regarding 1- and 5-year survival. Appropriate intergroup comparisons, univariate and multivariate analysis were made and P≤0·05 was considered statistically significant. There were no significant group differences in demographic data (except patient height). Despite the fact that median total blood loss did not differ between groups (111ml/kg in both groups), the Early group had greater levels of intraoperative RBC transfusion (75 vs. 59ml/kg, respectively, P=0·04) and less use of FFP (53 vs. 62ml/kg, respectively, P=0·01). Overall we noted a lower 1- and 5-year survival in the Early group (88·2% vs. 96%, P=0·04 and 82·4% vs. 89·1%, P=0·01, respectively). Univariate, but not multivariate regression analyses demonstrated that higher PELD score, RBC and FFP transfusion, and inclusion in the Early group were contributing factors to 1-year higher mortality. This retrospective analysis of blood loss and replacement in paediatric LT patients demonstrates that the majority of our patients suffer major haemorrhage and require large-volume RBC and FFP replacements. In our pilot study, large volume of RBC and FFP replacement did not contribute to mortality. Paediatric LT involves a number of multidisciplinary teams. Thus, all care-related factors and combinations thereof that may contribute to outcome and should be evaluated in the future.

Superior Outcomes and Reduced Wait Times in Pediatric Recipients of Living Donor Liver Transplantation.

Living donor liver transplantation (LDLT) is increasingly used to bridge the gap between the current supply and demand imbalance for deceased donor organs to provide lifesaving liver transplantation. Outcomes of 135 children who underwent LDLT were compared with 158 recipients of deceased donor liver transplantation (DDLT) at the largest pediatric liver transplant program in Canada. Recipients of LDLT were significantly younger than deceased donor recipients (P ≤ 0.001), less likely to require dialysis pretransplant (P < 0.002) and had shorter wait time duration when the primary indication was cholestatic liver disease (P = 0.003). The LDLT donors were either related genetically or emotionally (79%), or unrelated (21%) to the pediatric recipients. One-, 5-, and 10-year patient survival rates were significantly higher in LDLT (97%, 94%, and 94%) compared with DDLT (92%, 87%, and 80%; log-rank P = 0.02) recipients, as were graft survival rates (96%, 93%, and 93% for LDLT versus 89%, 81.4%, and 70%, respectively, for DDLT; log-rank P = 0.001). Medical and surgical complications were not statistically different between groups. Graft failure was higher in recipients of DDLT (odds ratio, 2.60; 95% confidence interval, 1.02, 6.58) than in the LDLT group after adjustment for clinical characteristics and propensity score. Living donor liver transplantation provides superior outcomes for children and is an excellent and effective strategy to increase the chances of receiving a liver transplant.

Development of a Pediatric Liver Transplant Program in a Developing Country

According to national transplant statistic in Colombia, Pediatric liver transplantation represent 20% (n=53) of the total of liver transplant performed in 2015. These numbers are growing in consequence with the improving clinical and surgical experience in this area, starting from liver reduction, split and living donation. Here in, we present our experience in the development as we consider, a complete liver pediatric transplant program in our institution. Materials and Methods Data represents a prospective cohort study of pediatric liver transplants, performed from 2007 to 2017 at Fundación Cardioinfantil, Bogota, Colombia. Data is presented according to the type of donor (Deceased: Reduced/Split, Living), age of the recipient and influence of a highly experience center support and accompaniment. Results and Discussion A total of 98 pediatric liver transplants were performed at our institution during this cohort. Fifty five percent of the patients received a transplant from a living donor. The main indications for transplantation were biliary atresia (42%), acute liver failure (9%), malignancy (8%) and cryptogenic cirrhosis (8%). Forty percent of the transplants were performed in children under 10kg. Main complications were arterial stenosis/thrombosis (3%), suprahepatic or portal vein thrombosis/stenosis (8%) and biliary complication (29%). The rate of 1-year biopsy proven acute moderate or severe rejection was 17%. There was a greater survival among living donor recipients (92% vs 72.9%; p 0.012) influenced by the learning curve and the support of a highly experienced center (before 71.4% vs after 87.1%; p 0.06). Conclusion Survival at our center is high compared with that obtained in similar studies in other countries. The support of a highly experienced center is important in order to achieve better results. Key words: Pediatric liver transplantation.

A Ten Year Retrospective Review of Infections in the First 12 Months Post Paediatric Liver and Liver-Kidney Transplantation at a Single Centre in Johannesburg, South Africa

Introduction Two paediatric liver transplant centres exist in South Africa, one in Johannesburg and the other in Cape Town. The programme in Johannesburg at Wits Donald Gordon Medical Centre (WDGMC) began in 2005 and is now the largest volume paediatric liver transplant unit in the country. WDGMC also hosts the only live donor paediatric liver transplant programme in sub-Saharan Africa. This research determined the incidence and profile of infectious events in the first year after transplantation. Materials and Methods This retrospective record review included paediatric liver and liver/kidney transplants from 2005-2015. The paediatric population was defined as any recipient <18 years of age on the day of transplant. Only laboratory confirmed infections were included. Ethics approval was obtained from the University’s Institutional Review Board. Information was sourced from clinical records and pathology reports. Statistical analysis was carried out using SAS version 9.4 with a 5% significance level. Results and Discussion There were 69 transplants in 65 patients.Most were female (42/69;61%), median age was 49 months (IQR 27-152) and biliary atresia was the most common indication for transplant (42%).A total of 253 infections occurred, mainly in the first three months after transplant. The most common site was bloodstream, followed by the abdomen and urinary tract. Bacterial infections occurred most commonly (193/253;76.3%). Of these, gram negative organisms predominated (120/193; 62.2%) and klebsiella species (50/120; 41.7%) was most frequently identified. In the gram positive group (72/193; 37.3%), enterococcus faecium predominated (25/72; 34.7%). Drug resistance was higher in the gram negative group (75.0%; 36/48) when compared to the gram positives (22.9% (11/48). Prevalence of viral infection was 16.6% (42/253) and fungal was 7.1% (18/253). Candida parapsilosis was the most commonly identified fungus. TB prophylaxis is not routinely administered and there was only one case of mycobacterial infection. This is the first study of its kind from sub-Saharan Africa. Gram negative infections were the most common, mirroring findings from the USA and Israel. What differed was that candida parapsilosis, not albicans, was the most frequently identified fungus and the most common primary site of infection was not the abdomen, but rather the bloodstream. Risk factors that may predispose to infection are severe malnutrition at the time of transplant and delayed referrals of young children with advanced disease. Conclusion Our findings suggest that standard TB prophylaxis may not be warranted, even in a country with high TB infection rates. This research has resulted in an urgent policy review in the transplant unit which has prioritised the nutritional status of children pre-transplant and implemented stringent infection control measures to prevent bloodstream infections. Study data were collected and managed using REDCap1 electronic data capture tools hosted at University of the Witwatersrand. This research was supported by Wits Donald Gordon Medical Centre, Johannesburg, South Africa. Data capture performed by the medical student group, Chanceplant from the University of the Witwatersrand.

A Report on the Positive Response to an Outdoor Nature Challenge of a Snow Camp for Young Liver Transplant Patients

ObjectivesMore than two decades have passed since the first living donor liver transplantation was performed in Japan in 1989. There are many reports about problems in adherence to taking medication and medical follow-ups in children who received liver transplants, because there is no transition strategy for those children and parents or guardians. The objective of this study is to measure the effect of nature and outdoor activity to improve children's medical adherence. MethodsWe recruited participants from 9-year-old children who are attending the outpatient liver transplant clinic in a stable condition (no event such as rejection or surgical procedure within 6 months). We took participants to a snow camp and measured its effect by using the IKIRU CHIKARA (IKR) tool, which contain 28 items divided into 3 categories: psychosocial ability, moral fitness, and physical ability. Children were tested on three occasions, before, just after, and 1 month after the camp. ResultsEight patients participated in the snow camp and 7 patients were eligible for the study. The average age was 12.6 with a range 10 to 17 years. There were 3 girls and 4 boys. The average IKR scores before, just after, and 1 month after the camp were 127.9, 131.5, and 126.6, respectively. ConclusionAn outdoor activity such as a snow camp can be safely conducted, and it is an acceptable option to incorporate within a pediatric liver transplant program. There were no significant changes in IKR scores during this short observation. Longer observation is needed to measure the effect of nature and outdoor activities.