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.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Preoperative risk factors for the early failure of the Kasai portoenterostomy in patients with biliary atresia.

PURPOSE: Biliary atresia is managed surgically by the Kasai portoenterostomy (KP). It has been reported by some groups that the outcomes of patients who have an early failed KP requiring a liver transplant (LTx) within the first year of life are worse than the outcomes of patients who undergo a primary LTx. The aim of this study was to identify preoperative parameters that could help predict what patients are at risk for the early failure of the procedure. MATERIALS AND METHODS: We conducted a retrospective chart review of all patients who underwent a KP between January 2008 and May 2018. The following preoperative parameters were analyzed: age at KP, anatomical variant of the biliary atresia, degree of liver fibrosis, CMV status, and PELD score. The main outcome of the study was the early failure of the KP (EF-K), which was defined as the need for LTx before 1 year of age, or BA-related death before 1 year of age. Second, we analyzed the risk factors associated with death without LTx within the first year of life. RESULTS: A total of 58 patients were included in the analysis. The native liver survival (NLS) was 56.5% and 48% at 1 and 5 years post KP, respectively. Overall survival (OS) was 79% and 76% at 1 and 5 years post KP, respectively. Early failure of KP occurred in 23 (39.7%) patients. OS in this group was 47% and 40% at 1 and 5 years, respectively. On the contrary, the OS of the remaining 35 (60.3%) patients was 100% at 1 and 5 years (P < 0.0001). When we compared all preoperative parameters, the only predictor of EF-K was the PELD score. When we analyzed the cases in the EF-K group who died without LTx, we found that the significant predictors were the cystic variant, a degree of liver fibrosis >4, and the PELD score. Nevertheless, on multivariate analysis, only PELD score was found as a statistically significant variable. CONCLUSION: Due to bad prognosis found in EF-K patients, we believe that it could be reasonable to offer them a primary LTx. PELD score was found to be the strongest preoperative parameter that allows predicting which patient will likely have an early failed KP. Further prospective and multicenter studies are needed to reinforce these results.

Childhood liver tumors in Argentina: Incidence trend and survival by treatment center. A report from the national pediatric cancer registry, ROHA network 2000-2015.

BACKGROUND: Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE: To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS: Newly diagnosed liver tumors cases are registered in the Argentine Pediatric Oncology Hospital Registry (ROHA) with an estimated coverage of 91% of national cases. Age-standardized incidence rate per millon (ASR) was calculated based on the National Vital Statistics Reports. Five-year overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare subgroup survival. RESULTS: Two hundred seven cases of hepatoblastoma (HB) and 73 of hepatocellular carcinoma (HCC) were identified. ASR of liver tumors was 1.8/million (95% confidence Interval [CI], 1.6-2.0) per year. ASR was 1.4 (1.2-1.6) for HB and 0.4 (0.3-0.5) for HCC. For HB, the highest incidence was found in the northwest region including the Altiplano. OS was 60.4% (53.4-66.8) for HB and 36.1% (25.2-47.2) for HCC. Five-year survival rate of children with metastatic HB treated at liver transplant hospitals (LTH) was 54.2% (30.3-73.0) compared to 13.3% (2.2-34.6) for those seen at other hospitals (OH) (P = .02), while for HCC this rate was 46.3% (30.7-60.6) at LTH compared to 17.5% (3.1-41.9) at OH (P = .01). CONCLUSIONS: The incidence rate of pediatric liver tumors was stable over the 16-year study period. Patients may benefit if at treatment initiation they are evaluated jointly with LTH specialists to define treatment strategies.

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.

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.

Magnetic Compression Anastomosis (Magnamosis) for Functional Undiversion of Ileostomy in Pediatric Patients.

INTRODUCTION: Magnamosis forms a compression anastomosis using self-aligning magnetic Harrison rings. The device has been approved by the Food and Drug Administration for first-in-human testing and has been applied in adults for intestinal anastomosis during urologic reconstructions. We now report the first cases of magnamosis to functionally undivert the fecal stream from a previously created loop ileostomy in pediatric patients. MATERIALS AND METHODS: Case 1: A 4-year-old male underwent a diverting loop ileostomy for malignant bowel obstruction. The obstruction gradually resolved with chemotherapy, and persistently high stomal output and malnutrition prompted undiversion. Case 2: A 16-year-old female with iloecolonic polyposis underwent ileoproctectomy with J pouch and diverting ileostomy. The magnamosis functional undiversion (FUN) technique involves introducing a Harrison ring through each stomal limb under general anesthesia with X-ray guidance. Magnets are each tied with sutures that exit the stoma and are then tied to each other externally. The device is removed when patency is detected. RESULTS: The introduction procedure took less than 20 minutes and there were no complications. Enteral feeding was initiated 24 and 6 hours postoperatively, and distal passage of stool occurred by the fourth and fifth days, respectively. Magnets were removed 14 and 15 days postoperatively, without evidence of leak. CONCLUSION: We conclude that the magnamosis undiversion procedure is a safe, minimally invasive way to gradually refunctionalize the excluded distal bowel after previous diverting ostomy.

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.

Ultrasonography, laboratory, and cholangiography correlation of biliary complications in pediatric liver transplantation.

The aim of this study is to correlate the US, laboratory, and cholangiography findings in pediatric liver transplant patients with biliary complications, trying to identify reliable decision-making tools for the management of these complications. Retrospective review was carried out of US results in 39 consecutive patients, from 2011 to 2013, with biliary complications after LT, documented by PTC. According to US biliary dilation, patients were classified as: mild, moderate, and severe, and according to laboratory findings as: normal or abnormal serum bilirubin and level of serum GGT. Data were correlated with PTC findings, divided in three groups: mild, moderate, and severe/occlusive BDS. There was no statistically significant correlation between the US findings and the laboratory findings and between US findings with PTC. There was a statistically significant correlation between GGT and cholangiography. In our series, abnormal US could not predict the severity of BDS on PTC. Bilirubin results were not able to predict the US findings either. GGT results demonstrated a statistically significant correlation with the severity of BDS found on PTC. These findings emphasize the role of GGT in the evaluation and decision of biliary interventions in pediatric liver transplant recipients.

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.

A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans.

During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.

Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program.

INTRODUCTION: Hepatitis A virus (HAV) infection is a vaccine-preventable disease. The most severe complication in children is fulminant hepatic failure (FHF), estimated to occur in 0.4% of cases; patients with FHF often require a liver transplant (LT). Following another outbreak of HAV infection in Argentina during 2003-2004, a one-dose HAV universal immunization (UI) program was started in 2005, resulting in a reduction in the incidence of HAV infection. We have investigated the impact of HAV UI on the trends in the occurrence of FHF and LT in children. METHODS: All pediatric cases of FHF admitted to four pediatric centers in Buenos Aires during March 1993-July 2005 were retrospectively reviewed, and data of cases during August 2005-December 2008 were collected. Information about demography, HAV infections and vaccination status, diagnostic data for FHF using the Pediatric Acute Liver Failure criteria, clinical laboratory results, encephalopathy, the severity of liver disease using the Pediatric End Stage Liver Disease score, assessment of patients on the LT waiting list using King's College Criteria for LT, treatment given for FHF (pre- and post-transplant), and clinical outcome were collected using a case report form. The frequency and outcomes of HAV-associated FHF and LT cases before and after UI were analyzed. RESULTS: During the pre-immunization period, March 1993-July 2005, 54.6% (N = 165) of FHF cases were caused by HAV; HAV-associated FHF cases peaked during 2003-2004. During the post-immunization period, August 2005-December 2008, only 27.7% (N = 18) of FHF cases were caused by HAV infection; only one of these patients had received the HAV vaccine (one dose only). The number of HAV-associated FHF cases decreased from 2005, and no cases were reported from November 2006-December 2008. Multivariate analyses showed that the association of FHF with HAV infection rather than other etiologies decreased with increasing age (P = 0.03), UI against HAV (P = 0.002), and anti-actin antibodies (P = 0.002), and increased with increasing weight (P = 0.0004). CONCLUSIONS: The number of children with HAV-associated FHF in Argentina has strongly decreased since the initiation of the UI program. Further monitoring is required to confirm the long-term health and economic benefits of UI against HAV infection.

[Neonatal hemochromatosis. A cause of liver failure in utero. Report of two cases and review of the literature]. / Hemocromatosis neonatal. Una causa de fallo hepático in útero. Presentación de dos casos y revisión de la bibliografía.

Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra- hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. It's a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.

Hemocromatosis Neonatal: una causa de fallo hepático in utero: presentación de dos casos y revisión de la bibliografía / Neonatal Hemochromatosis: a cause of liver failure in utero: report of two cases and review of the literature

La hemocromatosis neonatal es una entidad clínico patológicaque presenta fallo hepático grave, se inicia in útero, asociada a siderosis intrahepática y extrahepática, que respeta el sistema reticulo endotelial.Su causa se desconoce pero se debería a un manejo anormal del hierro fetoplacentario con enfermedad hepática perinatal, relación genética familiar o sería consecuencia de una enfermedad gestacional aloinmunitaria. Es un síndrome con características comunes más que una simple entidad patológica, con transmisión materna y alta recurrencia en la misma progenie. La muerte se produceen los primeros días o semanas de vida por fallomultiorgánico. Presentamos dos recién nacidos con hemocromatosis neonatal. El primero falleció por fallo multiorgánico y el segundo permitió el trasplante hepático. Desde 1993, se emplea un cocktail antioxidantequelantedel hierro, junto al tratamiento de soporteestándar del fallo hepático, pero su uso es polémico. En 2002, una comunicación preliminar sugiere que el tratamiento con inmunoglobulinas endovenosas en la segunda mitad de la gestación, en mujeres con el antecedente de un hijo con hemocromatosis neonatal probada, previene las formas recurrentes letales de la enfermedad. Este trastorno se debe sospechar en todo fallo hepático grave al nacer, acompañado de valores séricos de ferritina elevados; pero debe confirmarse por un aumento de los depósitos hepáticos de hierro y siderosis extrahepática demostrables por resonancia magnética nuclear, en la biopsia de glándulas salivales o en la autopsia. La hemocromatosis neonatal es la indicación específicamás frecuente de trasplante hepático en los primeros 3 meses de vida, que parecería ser el tratamiento de elección por considerar desde el momentoque el soporte médico, incluida la terapia antioxidante-quelante del hierro, sea inefectivo, antes de que surjan complicaciones neurológicas irreversibles (AU)

Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. Itãs a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.(AU)

Hemocromatosis Neonatal: una causa de fallo hepático in utero: presentación de dos casos y revisión de la bibliografía / Neonatal Hemochromatosis: a cause of liver failure in utero: report of two cases and review of the literature

La hemocromatosis neonatal es una entidad clínico patológicaque presenta fallo hepático grave, se inicia in útero, asociada a siderosis intrahepática y extrahepática, que respeta el sistema reticulo endotelial.Su causa se desconoce pero se debería a un manejo anormal del hierro fetoplacentario con enfermedad hepática perinatal, relación genética familiar o sería consecuencia de una enfermedad gestacional aloinmunitaria. Es un síndrome con características comunes más que una simple entidad patológica, con transmisión materna y alta recurrencia en la misma progenie. La muerte se produceen los primeros días o semanas de vida por fallomultiorgánico. Presentamos dos recién nacidos con hemocromatosis neonatal. El primero falleció por fallo multiorgánico y el segundo permitió el trasplante hepático. Desde 1993, se emplea un cocktail antioxidantequelantedel hierro, junto al tratamiento de soporteestándar del fallo hepático, pero su uso es polémico. En 2002, una comunicación preliminar sugiere que el tratamiento con inmunoglobulinas endovenosas en la segunda mitad de la gestación, en mujeres con el antecedente de un hijo con hemocromatosis neonatal probada, previene las formas recurrentes letales de la enfermedad. Este trastorno se debe sospechar en todo fallo hepático grave al nacer, acompañado de valores séricos de ferritina elevados; pero debe confirmarse por un aumento de los depósitos hepáticos de hierro y siderosis extrahepática demostrables por resonancia magnética nuclear, en la biopsia de glándulas salivales o en la autopsia. La hemocromatosis neonatal es la indicación específicamás frecuente de trasplante hepático en los primeros 3 meses de vida, que parecería ser el tratamiento de elección por considerar desde el momentoque el soporte médico, incluida la terapia antioxidante-quelante del hierro, sea inefectivo, antes de que surjan complicaciones neurológicas irreversibles

Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. It’s a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.