Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation.

AIMS: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. METHODS: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. RESULTS: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CLMAX  = 4.1 L/h) at 4.6 days post-transplantation (T50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h-1 ) and a 24% reduction in bioavailability (FNS ) at 14 days post-transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first-pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50 ). CONCLUSION: A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post-transplant time on clearance and the sedation status may be considered in routine dosing management.

Prognostic Factors in Pediatric Early Liver Retransplantation.

The most common indications for early liver retransplantation (eRe-LT) are vascular complications and primary nonfunction (PNF). These patients are usually in a critical clinical condition that can affect their chances of survival. In fact, the survival of these patients is usually lower compared with the patients undergoing a first transplant. To the best of our knowledge, no specific series of pediatric patients undergoing eRe-LT has been published to date. Therefore, the aim of this study is to report the results of eRe-LT and to analyze factors potentially related to success or failure. Our work is of a retrospective cohort study of patients who underwent eRe-LT at the Juan P. Garrahan Pediatric Hospital of Buenos Aires, Argentina, between May 1995 and December 2018 (n = 60). Re-LT was considered early when performed ≤30 days after the previous LT. A total of 40 (66.7%) patients were enrolled due to vascular causes and 20 (33.3%) were enrolled because of PNF. Of all the relisted patients, 36 underwent eRe-LT, 14 died on the waiting list, and 10 recovered without eRe-LT. A total of 23 (63.9%) patients died after eRe-LT, most of them due to infection-related complications. Survival rates at 1 and 5 years were 42.4% and 33.9%, respectively. On univariate logistic regression analysis, Pediatric End-Stage Liver Disease (PELD)/Model for End-Stage Liver Disease (MELD) scores, transplant era, and advanced life support at eRe-LT were found to be related to 60-day mortality. However, on multivariate analysis, era (odds ratio [OR], 9.3; 95% confidence interval [CI], 1.19-72.35; P = 0.033) and PELD/MELD scores (OR, 1.07; 95% CI, 1-1.14; P = 0.036) were significantly associated with 60-day patient mortality. This study found that the level of acuity before retransplant, measured by the requirement of advanced life support and the PELD/MELD score at eRe-LT, was significantly associated with the chances of post-eRe-LT patient survival.

Changing Etiologies and Prognostic Factors in Pediatric Acute Liver Failure.

After the implementation of universal hepatitis A virus vaccination in Argentina, the outcome of pediatric acute liver failure (PALF) remains unknown. We aimed to identify variables associated with the risk of liver transplantation (LT) or death and to determine the causes and short-term outcomes of PALF in Argentina. We retrospectively included 135 patients with PALF listed for LT between 2007 and 2016. Patients with autoimmune hepatitis (AIH), Wilson's disease (WD), or inborn errors of metabolism (IEM) were classified as PALF-chronic liver disease (CLD), and others were classified as "pure" PALF. A logistic regression model was developed to identify factors independently associated with death or need of LT and risk stratification. The most common etiologies were indeterminate (52%), AIH (23%), WD (6%), and IEM (6%). Overall, transplant-free survival was 35%, whereas 50% of the patients underwent LT and 15% died on the waiting list. The 3-month risk of LT or death was significantly higher among patients with pure PALF compared with PALF-CLD (76.5% versus 42.5%; relative risk, 1.8 [1.3-2.5]; P < 0.001), and 3 risk factors were independently associated with worse outcome: international normalized ratio (INR) ≥3.5 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.2]), bilirubin ≥17 mg/dL (OR, 4.4; 95% CI, 1.9-10.3]), and pure PALF (OR, 3.8; 95% CI, 1.6-8.9). Patients were identified by the number of risk factors: Patients with 0, 1, or ≥2 risk factors presented a 3-month risk of worse outcome of 17.6%, 36.6%, and 82%, respectively. In conclusion, although lacking external validation, this simple risk-staging model might help stratify patients with different transplant-free survival rates and may contribute to establishing the optimal timing for LT.

Prognostic factors for event-free survival in liver transplantation for hepatoblastoma: A single-center experience.

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Twenty percent of the cases may remain unresectable after neoadjuvant chemotherapy and, for these patients, liver transplant (LT) is an accepted therapeutic option. To analyze the risk factors to event-free survival (EFS) that influence the clinical outcome of patients with HB receiving LT, we retrospectively analyzed 21 patients with HB who underwent LT between January 1, 2005, and May 1, 2018. Overall survival (OS) was 90%. The univariate analysis shows that the AFP level at the time of LT was associated with a higher risk of EFS. With a ROC curve analysis, we established a cutoff point value of AFP levels at 16 000 ng/dL, with a sensitivity of 71.43% and a specificity of 85.71%. Multivariate analysis showed that patients with higher values of pretransplant AFP (>16 000 ng/dL) had a significantly higher risk of EFS than those transplanted with lower levels (HR: 10.180; 95% CI: 1.54-66.97; P = .02). Efforts should be made to improve the selection of candidates for LT for unresectable HB, aiming at a better definition of chemoresistance as a risk factor of poor outcomes.

Identification of Factors Affecting Tacrolimus Trough Levels in Latin American Pediatric Liver Transplant Patients.

Tacrolimus is the cornerstone in pediatric liver transplant immunosuppression. Despite close monitoring, fluctuations in tacrolimus blood levels affect safety and efficacy of immunosuppressive treatments. Identifying the factors related to the variability in tacrolimus exposure may be helpful in tailoring the dose. The aim of the present study was to characterize the clinical, pharmacological, and genetic variables associated with systemic tacrolimus exposure in pediatric liver transplant patients. De novo transplant patients with a survival of more than 1 month were considered for inclusion and were genotyped for cytochrome P450 3A5 (CYP3A5). Peritransplant clinical factors and laboratory covariates were recorded retrospectively between 1 month and 2 years after transplant, including alanine aminotransferase (ALT), aspartate aminotransferase, hematocrit, and tacrolimus predose steady-state blood concentrations collected 12 hours after tacrolimus dosing. A linear mixed effect (LME) model was used to assess the association of these factors and the log-transformed tacrolimus dose-normalized trough concentration (logC0/D) levels. Bootstrapping was used to internally validate the final model. External validation was performed in an independent group of patients who matched the original population. The developed LME model described that logC0/D increases with increases in time after transplant (ß = 0.019, 95% confidence interval [CI], 0.010-0.028) and ALT values (ß = 0.00030, 95% CI, 0.00002-0.00056), whereas logC0/D is significantly lower in graft CYP3A5 expressers compared with nonexpressers (ß = -0.349, 95% CI, -0.631 to -0.062). In conclusion, donor CYP3A5 genotype, time after transplant, and ALT values are associated with tacrolimus disposition between 1 month and 2 years after transplant. A better understanding of tacrolimus exposure is essential to minimize the occurrence of an out-of-range therapeutic window that may lead to adverse drug reactions or acute rejection.

Survival Time to Biopsy-Proven Acute Rejection and Tacrolimus Adverse Drug Reactions in Pediatric Liver Transplantation.

BACKGROUND: Despite advances in surgical procedures and the optimization of immunosuppressive therapies in pediatric liver transplantation, acute rejection (AR) and serious adverse drug reaction (ADR) to tacrolimus still contribute to morbidity and mortality. Identifying risk factors of safety and efficacy parameters may help in optimizing individual immunosuppressive therapies. This study aimed to identify peritransplant predictors of AR and factors related to the risk of ADR to tacrolimus in a large Latin American cohort of pediatric liver transplant patients. METHODS: We performed a retrospective cohort study in a pediatric liver transplant population (n = 72). Peritransplant variables were collected retrospectively including demographic, clinical, laboratory parameters, genomic (CYP3A5 donor and recipients polymorphism), and tacrolimus trough concentrations (C0) over a 2-year follow-up period. Variability in tacrolimus C0 was calculated using percent coefficient of variation and tortuosity. ADR- and AR-free survival rates were calculated using the Kaplan-Meier method, and risk factors were identified by multivariate Cox regression models. RESULTS: Cox-proportional hazard models identified that high tortuosity in tacrolimus C0 was associated with an 80% increased risk of AR [hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.01-3.22; P < 0.05], whereas steroid in maintenance doses decreased this risk (HR, 0.56; 95% CI, 0.31-0.99; P < 0.05). Forty-six patients experienced at least one ADR including hypomagnesemia, nephrotoxicity, hypertension, malignancies, and tremor as a first event. Multivariate analysis showed that C0 values 10 days before the event (HR, 1.25; 95% CI, 1.21-1.39; P < 0.0001) and CYP3A5 expresser recipients (HR, 2.05; 95% CI, 1.03-4.06; P < 0.05) were independent predictors of ADR. CONCLUSIONS: Tacrolimus C0 values, its variability, and CYP3A5 polymorphisms were identified as risk factors of AR and tacrolimus ADR. This knowledge may help to control and reduce their incidence in pediatric liver transplant patients. Prospective studies are important to validate these results.

Waiting list outcome of Peld/Meld exceptions: A single-center experience in Argentina.

As PELD/MELD-based allocation policy was adopted in Argentina in 2005, a system of exception points has been in place in order to award increased waitlist priority to those patients whose severity of illness is not captured by the PELD/MELD score. We aimed to investigate the WL outcome of patients with granted PELD/MELD exceptions. A retrospective cohort study was conducted in children under 18 years old. WL outcomes were evaluated using univariable analysis. From 07/2005 to 01/2014, 408 children were listed for LT. There were 304 classified by calculated PELD/MELD. During this time, 85 (30%) PELD/MELD exceptions were granted. In this cohort, 89.4% (76 of 85) were transplanted and 7.1% (6 of 85) died while on the WL. The remaining 3 pts (3.5%) were removed from the WL due to other causes. We compared the impact of PELD/MELD exceptions in those 85 patients to outcomes in 87 non-exception patients with PELD/MELD ≥19 points. Patients with the exception had significantly better access to WL and lower WL mortality. Our data suggest that children listed by PELD/MELD exceptions had an advantage compared to children with CLD with equivalent PELD/MELD listing priorities.

Pharmacoepidemiology of tacrolimus in pediatric liver transplantation.

AEs during immunosuppressive treatment with tacrolimus are very common. We retrospectively evaluated FK safety and efficacy in a large pediatric liver transplant cohort in Latin America. During 2-year follow-up, we analyzed data from patients who underwent liver transplantation over the period 2010-2012 and recorded FK exposure, AEs, and AR episodes. AEs were classified according causality and severity. Tacrolimus exposure before and during AE was compared using Wilcoxon matched-pairs test. Kaplan-Meier curves were used for survival analysis. In total, 46 patients (out of 72 patients) experienced 69 AEs, such as hypomagnesemia (49%), PTLD (6%), hypertension (6%), and/or nephrotoxicity (22%). 43% of AEs were classified as moderate or serious, and 89% were assigned as probable or definitive. Patients who had one or more AR episodes accounted for 65%. The 12-month acute rejection-free survival was 41% (95% CI, 30.1%-53.1%). A significant difference was observed in FK trough concentrations before and during hypomagnesemia and nephrotoxicity (P<.05). This study is the first report of FK safety in a large group of pediatric liver transplant patients in Latin America. Children experience AEs, even in protocols with low FK doses. Therapeutic monitoring is an important tool to manage immunosuppressive schemes containing tacrolimus in vulnerable populations.

Split liver transplantation: Report of right and left graft outcomes from a multicenter Argentinean group.

Grafts from split livers (SLs) constitute an accepted approach to expand the donor pool. Over the last 5 years, most Argentinean centers have shown significant interest in increasing the use of this technique. The purpose of this article is to describe and analyze the outcomes of right-side grafts (RSGs) and left-side grafts (LSGs) from a multicenter study. The multicenter retrospective study included data from 111 recipients of SL grafts from between January 1, 2009 and December 31, 2013. Incidence of surgical complications, patient and graft survival, and factors that affected RSG and LSG survival were analyzed. Grafts types were 57 LSG and 54 RSG. Median follow-up times for LSG and RSG were 46 and 42 months, respectively. The 36-month patient and graft survivals for LSG were 83% and 79%, respectively, and for RSG were 78% and 69%, respectively. Retransplantation rates for LSG and RSG were 3.5% and 11%, respectively. Arterial complications were the most common cause of early retransplantation (less than 12 months). Cold ischemia time (CIT) longer than 10 hours and the use of high-risk donors (age ≥ 40 years or body mass index ≥ 30 kg/m2 or ≥ 5 days intensive care unit stay) were independent factors for diminished graft survival in RSG. None of the analyzed variables were associated with worse graft survival in LSG. Biliary complications were the most frequent complications in both groups (57% in LSG and 33% in RSG). Partial grafts obtained from liver splitting are an excellent option for patients in need of liver transplantation and have the potential to alleviate the organ shortage. Adequate donor selection and reducing CIT are crucial for optimizing results.

Results after the adoption of a MELD/PELD-based liver allocation policy in Argentina.

In July 2005, Argentina switched from a categorical liver allocation system to a MELD/PELD-based policy for patients with CLD. To analyze WL outcomes and survival after LT in children. From January 2000 to December 2010, 923 children were registered. Two consecutive five-yr periods were analyzed and compared: Era I (January 2000-July 2005) (n = 379) and Era II (July 2005-December 31, 2010) (n = 544). All data were prospectively collected and analyzed using the Kaplan-Meier method. After adopting the MELD/PELD system, WL registrations increased by 44% (from 379 to 544) and the number of LT increased by only 24% (from 278 to 365). However, three-month WL mortality rate (32% to 18%, p < 0.0001, HR 2.002 CI 95% 1.5-2.8) decreased significantly. No significant differences were observed between Era 1 and II in one-yr post-LT survival (77.5% vs. 84.1%, p = 0.3053) and in acute re-LT rate (9% vs. 5%, p = 0.1746). Under the MELD/PELD-based allocation system in Argentina, mortality on the WL significantly decreased in children with CLD without affecting post-LT survival, although reduced access to LT was observed.

Cambio cultural en cirugía pediátrica: de la teoría a la práctica / Cultural change in pediatric surgery: from theory to practice

Introduccion: La implementación de cambios organizacionales en los servicios de cirugía pediátrica implica la necesidad de una transformación cultural de los cirujanos y de la organización hospitalaria. Luego del análisis situacional realizado en el año 2008 en nuestro servicio se implementó un cambio organizacional a través de una gestión por proceso con un enfoque sistémico. El objetivo de este trabajo es describir los resultados del cambio cultural realizado. Población y métodos: estudio retrospectivo tipo antes-después de los cambios realizados luego del año 2009. Para evaluar los resultados se compararon los trasplantes realizados a partir del cambio a un igual número de trasplantes previos. Se compararon en base a indicadores de productividad y performance. Los principios guías de las acciones de cambio fueron generar una visión compartida, crear un lenguaje en común, impulsar la participación, el compromiso y la creatividad, y medir los resultados. Resultados: se aumento la productividad, se mejoró la performance y se ampliaron los servicios ofrecidos al paciente. Conclusiones: el proceso de cambio instaurado implico la implementación de un sistema de aprendizaje continuo basado en la estrategia de Planificar/Hacer/Chequear y Actuar. Esta experiencia inicial ha demostrado una mejora en los indicadores de productividad y performance. Resta dilucidar la sustentabilidad de los cambios, su efecto en la satisfacción de los equipos tratantes y pacientes, así como la posibilidad de reproducir esta experiencia en servicios quirúrgicos pediátricos.

ntroduction: The implementation of organizational changes in departments of pediatric surgery warrant the need for culteral transformation of the surgeons and the hospital organization. After a situational assessment conducted in 2008, an organi-zational change was implemented in our department through a planned systemic change process. The aim of this study was to describe the results of the cultural change achieved. Population and methods: A retrospective before-and-after study of the changes introduced since 2009 was conducted. To evaluate the results, transplants performed since the in-troduction of the changes (case group:A) were compared to a similar number of transplants performed previously (control group:B). The groups were compared according to markers of productivity (n of trasplants/period) and performance (post-rasplant survival). Action guidelines were to create a shared vision and common language, to encourage participation, commitment, and creativity, and to measure results. Results: Productivity increased (A: 61 Tx in 23 months, B: 61 Tx in 28 months), performance improved (survival A: 83.5%. vs B: 78%), and services offered to the patients were enhanced. Conclusions: The established change process resulted in the implementation of a continuous learning system based on the strategy of Plan/Do/Check and Act (Deming circle). The initial experience has shown improved markers of productivity and performance. Future evaluation will elucidate sustainability of the changes, their effect on treating-team and patient satisfac-tion, as well as the possibility to reproduce the experience in pediatric surgery departments.

Post-transplant lymphoproliferative disorder after pediatric liver transplantation: characteristics and outcome.

UNLABELLED: Post-Transplant Lymphoproliferative Disorder (PTLD) is a life threatening complication in organ transplant recipients. Risk factors include primary Epstein-Barr virus infection, intensity of immunosupression and cytomegalovirus infection. OBJECTIVES: To evaluate the incidence, clinical presentation, risk factors, histopathologic appearance and outcome of pediatric liver recipients with PTLD at our institution. METHOD: Retrospective, descriptive and observational analysis. Between November 1992 and December 2005, 383 liver transplants were performed. The diagnosis of PTLD was based on clinical history and physical examination and confirmed by histologic appearance and immunohistologic staining. Knowles' classification was used for histopathologic diagnosis. RESULTS: The incidence of PTLD was 5.7% (n: 22p). The average onset after tansplantation (OLT) was 24.9 months. Clinical manifestations were malaise, anorexia, fever of more than 3 days, peripheral adenopathy, tonsillar hypertrophy, abdominal mass, hepatosplenomegaly, snoring, interstitial pulmonary infiltrate, G.T.-tract bleeding, rash, submaxilar mass. Histopathologic diagnosis were Plasmocytic Hyperplasia (n: 10), Polymorphic Lymphoproliferative Disorder (n: 8), Non-Hodgkin Lymphoma (n: 4). Mortality was 18%. CONCLUSION: The clinical presentations were protean and not specific. A high index of suspicion is important for early diagnosis as it correlates with more benign lesions and more favorable outcume. The lower mortality rate in our series is concordant with that reported in more recent articles.

Bipartición hepática: resultados iniciales / Split liver transplantation

Introducción: Debido a la escasez de donantes cadavéricos se han desarrollado técnicas quirúrgicas para aumentar el pool de donantes. Una de ellas es la bipartición hepática (BH). Objetivo: Analizar los resultados y evolución alejada de una serie de BH. Lugar: Hospitales públicos. Material y Método: Entre enero de 1992 y julio de 2004 fueron realizados 613 trasplantes hepáticos. De ellos 35 (5,7 por ciento) fueron realizados con una BH. Se analizan complicaciones quirúrgicas, supervivencia del injerto y del paciente al año y los 5 años. Los resultados se agrupan según el injerto utilizado (seccionectomía lateral izquierda, SLI y triseccionectomía derecha, TSD). Resultados: 22 injertos fueron implantados en pacientes pediátricos y 13 en adultos. Se utilizaron 15 TSD y 20 SLI. TSD: Tres pacientes (20 por ciento) presentaron necrosis del segmento 4, dos (13,3 por ciento) fueron reoperados por hemoperitoneo. Existieron 2 trombosis arteriales (13,3 por ciento). Cuatro pacientes (26,6 por ciento) presentaron complicaciones biliares, 2 fístulas y 2 estenosis no anastomóticas. El seguimiento medio fue 45 meses. La supervivencia actuarial al año del injerto y paciente fue 66 por ciento y 73 por ciento y a los 5 años 55 por ciento y 61 por ciento. SLI: Tres pacientes fueron reoperados por hemoperitoneo. Se presentaron 3 trombosis arteriales, 2 portales y 9 (45 por ciento) complicaciones biliares: 7 fístulas y 2 estenosis. El tiempo medio de seguimiento fue 61 meses, con una supervivencia del injerto al año del 65 por ciento y a los 5 años del 59 por ciento. La supervivencia del paciente al año y a los 5 años fue 70 por ciento. Conclusiones: La BH es posible y se puede realizar con un índice aceptable de complicaciones similares a las del trasplante con hígado entero y donante vivo

Mortality risk score in liver transplantation: changes over time in its predicting power.

UNLABELLED: Since the onset of our liver transplantation program in 1992, 362 transplants were performed in 338 children. A risk score for predicting mortality was designed and implemented over time. The description of a method utilized to design the risk score, changes in mortality rate over 12 yr and the analysis of factors that might have influenced these changes are presented and discussed in this paper. PATIENTS AND METHODS: Cox regression analysis was applied to a retrospective sample of 110 patients with liver cirrhosis, transplanted between 1992 and 2000. A risk score was prepared using beta coefficients of the two significant variables related to survival time: age (1.08, p=0.02) and bilirubin levels (0.93, p=0.03), and two groups were identified: low- and high-risk score. The score was applied in two consecutive samples: 2000-2002 and 2002-2004. RESULTS: In the first sample (1992-2000), we found 69 and 41 as low- and high-risk patients, with a median survival time of 93.13 and 2.93 months (p=0.0001). In the 2000-2002 sample, a median survival time of 41.7 and 2.33 months (p=0.03) was found for low- and high-risk groups, respectively. In the third sample (2002-2004), there was a remarkable decrease in mortality in the high-risk group (n=29) and the score did not discriminate between high- and low-risk groups (p=0.35). CONCLUSION: A scoring system to identify risk levels in liver transplantation patients is an operative and powerful tool during a given period of time but it has to be updated as risk factors will vary following the team's learning curve.

[Evolution of children one year post liver transplant]. / Evolución de niños post-trasplante hepático luego del primer año de sobrevida.

Orthotopic liver transplantation is the only definitive mode of therapy for children with end-stage liver disease. However, it remains challenging because of the necessity to prevent long-term complications. The aim of this study was to analyze the evolution of transplanted patients with more than one year of follow up. Between November 1992 and November 2001, 238 patients underwent 264 liver transplantations. A total of 143 patients with more than one year of follow up were included. The median age of patients +/- SD was 5.41 years +/- 5.26 (r: 0.58-21.7 years). All children received primary immunosuppression with cyclosporine. The indications for liver replacement were: fulminant hepatic failure (n: 50), biliary atresia (n: 38), cirrhosis (n: 37), chronic cholestasis (n: 13) and miscellaneous (n: 5). The indications for liver re-transplantation were: biliary cirrhosis (n: 7), hepatic artery thrombosis (n: 4) and chronic rejection (n: 3). Reduced-size liver allografts were used in 73/157 liver transplants, 14 of them were from living-related donors and 11 were split-livers. Patient and graft survival rates were 93% and 86% respectively. Death risk was statistically higher in retransplanted and reduced-size grafted patients. Growth retardation and low bone density were recovered before the first 3 years post-transplant. The incidence of lymphoproliferative disease was 7.69%. De novo hepatitis B was diagnosed in 7 patients (4.8%). Social risk did not affect the outcome of our population. The prevention, detection and early treatment of complications in the long-term follow up contributed to improve the outcome.

Variantes anatómicas de la arteria hepática: la importancia de su reconocimiento en la cirugía digestiva / Anatomic variants of the hepatic artery: importance for the digestive surgery

Objetivo: describir las variantes anatómicas de la arteria hepática, resaltar su importancia en la cirugía digestiva y sugerir pautas para su reconocimiento tanto pre como intraoperatorio. Lugar de aplicación: dos hospitales públicos de alta complejidad. Diseño: longitudinal, retrospectivo, descriptivo. Población: 414 hígados para ser implantados en receptores de Trasplante Hepático, 374 fueron obtenidos de donante cadavéricos y 40 segmentados laterales izquierdo de donante vivo relacionado. Método: se disecaron y clasificaron de acuerdo a su disposición anatómica (según la clasificación propuesta por Michels y modificada por Hiatt) todas las arterias hepáticas de 374 hígados obtenidos de donante cadavérico y 40 de donante vivo relacionado. Resultados: encontramos un 70,7 por ciento de variantes tipo I (distribución normal), 10,6 por ciento tipo II (rama izquierda de la coronaria estomáquica), 7 por ciento tipo III (rama derecha de la Mesentérica superior), 4,8 por ciento tipo IV (triple arteria), 2 por ciento tipo V (hepática común de Mesentérica), 0,8 por ciento tipo VI (hepática común directa de aorta) y 4 por ciento otras variantes no clasificadas. Conclusión: las variantes anatómicas de la arteria hepática son más frecuentes de lo que uno puede esperar y rondan entre el 25 y 40 por ciento. Es importante su estudio preoperatorio y su reconocimiento intraquirúrgico para evitar lesiones de alguna de sus ramas que deriven en consecuencias graves e irreversibles tanto sobre la vía biliar como el hígado