"Current state and prospects in managing liver transplanted children".

Pediatric liver transplantation (LTx) has revolutionized life chances and perspectives of children with liver disease. Following rapid establishment of the therapeutic concept in the early years of pediatric transplant medicine, more aspects beyond plain survival become increasingly important. In addition to improving the short to medium-term survival rates, researchers are focusing on themes such as rehabilitation, adherence and quality of life, long-term graft fibrosis and dysfunction, as well as the consequences of long-term immunosuppression. Also, more protocol biopsy data are available to evaluate increasing graft fibrosis. To manage their conditions, patients will need access to highly experienced pediatric liver transplant centers where clinical research will examine modulators of renal disease, endocrine and cardiovascular comorbidity and the development of graft fibrosis and malignancies. Assessment and evaluation of health-related quality of life and factors which influence clinical tolerance, adherence and transition from child to adult care will also be investigated. The analysis of multi-national registry data and more than 40years of experience with large patient cohorts will provide important clues to treatment and will thus get increasing attention. In the future, longitudinal assessment of the outcome for pediatric LTx patients should include more functional aspects than plain survival rates or laboratory parameters.

Mortalidad infantil en un hospital de nivel terciario. Limitación de esfuerzo terapéutico, correspondencia clínico-patológica y precisión diagnóstica / Infant mortality in a third level paediatric hospital. therapeutic effort limitation, clinical-pathological agreement and diagnostic accuracy

Objetivo: Analizar la mortalidad en un hospital infantil de tercer nivel y alta complejidad. Material y métodos: Se revisaron los fallecidos en el Hospital Infantil La Paz durante los años 2007, 2008 y 2009. Se analizaron datos epidemiológicos, diagnósticos clínicos y de autopsia y su correspondencia, y si se llegaba a un diagnóstico etiológico definitivo. La limitación del esfuerzo terapéutico y la previsibilidad del fallecimiento también fueron recogidas. Las variables fueron prospectivamente definidas al inicio. Resultados: Se estudiaron 253 fallecimientos (6,08 por mil ingresos). El 43,4% eran menores de 1 mes y el 63,9% menores de un año. La patología neonatal y la hemato-oncológica fueron las causas más frecuentes. Fallecieron en las tres unidades de cuidado intensivo el 87%. Se practicó autopsia a 53% de los fallecidos y se detectó un 7,8% de nuevos hallazgos significativos, aunque solo en un caso podría el tratamiento haber modificado el pronóstico. Limitación de esfuerzo terapéutico y cuidado paliativo se instauró en el 41,9%. El fallecimiento era esperado al inicio del proceso en 83,9%, En 92% se consideró que existía un diagnóstico definitivo y en 86,4% un diagnóstico etiológico de los procesos que condujeron al fallecimiento. Conclusiones: El análisis de la mortalidad hospitalaria permite evaluar la calidad de la asistencia pediátrica y detectar resultados adversos. La autopsia continúa proporcionando información relevante. La limitación de esfuerzo terapéutico y cuidado paliativo es una medida cada vez más frecuente en la edad pediátrica. El número de niños que muere sin diagnóstico etiológico sigue siendo alto(AU)

Objective: To study infant and child mortality in a third level children's hospital treating highly complex patients. Patients and methods: All children dying in the period 2007- 2009 at La Paz Children's Hospital were evaluated. Epidemiological data, autopsy rate, clinical and autopsy diagnoses and their correspondence and the number of, patients with precise final diagnoses were analysed. Therapeutic effort limitation and palliative care were also evaluated as well as if the final result was expected according to the initial disease or clinical condition of the patients. All the variables were prospectively defined at the start of the study period. Results: A total of 253 cases (6.08‰ admissions) were analysed. The two leading causes of death were disorders related to prematurity and low birth weight, and haematology oncology malignant diseases. Most patients (87%) died in an intensive care unit (neonatal or paediatric). During the study period 134 autopsies (53%) were performed, and new clinically significant findings were observed in 12 of these (7.8%) but in only one case the treatment could have possibly modified the prognosis (class I discrepancy). Therapeutic effort limitation and palliative care were implemented in 41.9%. Death was initially expected in 83.9% of cases. An accurate final diagnosis was defined in 92%, and the aetiology of the disease was considered to be identified in 86.4% of all deaths. Conclusions: Hospital mortality analysis is useful to evaluate the quality of the paediatric care and to detect adverse results that could be corrected. Paediatric autopsy continues to provide clinically significant data for paediatricians and families. Therapeutic effort limitation and palliative care is increasingly applied in paediatric end of life care. The number of infants and children dying without a final aetiological diagnosis is still considerably high(AU)

Liver transplantation in children with cystic fibrosis: experience in our centre and preliminary results with a combined en bloc liver-pancreas graft.

AIM OF THE STUDY: Cystic fibrosis (CF) is a multisystemic disease, with some patients developing end-stage liver disease (ESLD), requiring liver transplantation (LT). These children usually present with severe mutations of the CFTR gene. Almost 100% of patients with severe mutations develop exocrine pancreatic insufficiency, leading later to endocrine insufficiency. Immunosuppression accelerates the development of insulin-dependent diabetes (IDD) in transplanted children with CF. Our aims were: (1) to analyze our experience with CF-related ESLD children who received LT, and the relationship to the development of IDD; (2) to report our preliminary results with en bloc liver-pancreas transplantation (CLPT). METHODS: 9 children (6M/3F) with CF and ESLD underwent LT between 1993 and 2010; median age and weight were 12.3 years (range: 5.4-17.0) and 36.7 kg (range: 14.2-58.5), respectively. 4 patients received a whole graft, 4 had reduced grafts (1 split) and 1 underwent CLPT. Immunosuppression followed the protocols at the time of transplantation. RESULTS: Liver function was restored in all patients and none of them needed re-transplantation. Median follow-up was 105 months (range: 4-206). 1 child died of respiratory failure at 23 months after transplantation while awaiting pulmonary transplantation. Survival (Kaplan-Meier) at 105 months was 87.5%. 4 children already had IDD before transplantation and 3 developed diabetes immediately after transplantation. 2 had not developed IDD at the end of the study: the youngest at the time of LT (5.4 years, follow-up 7.1 years) and the girl who had had CLPT and who recovered normal exocrine and endocrine pancreatic function after transplantation. CONCLUSIONS: LT is a realistic option to treat CF-related ESLD children. IDD is common in these patients. En bloc liver-pancreas transplantation is an appealing option, since it simultaneously restores exocrine function and prevents IDD. This procedure has clear technical advantages over simultaneous isolated liver and pancreas transplantation.

[Infant mortality in a third level paediatric hospital. therapeutic effort limitation, clinical-pathological agreement and diagnostic accuracy]. / Mortalidad infantil en un hospital de nivel terciario. Limitación de esfuerzo terapéutico, correspondencia clínico-patológica y precisión diagnóstica.

OBJECTIVE: To study infant and child mortality in a third level children's hospital treating highly complex patients. PATIENTS AND METHODS: All children dying in the period 2007- 2009 at La Paz Children's Hospital were evaluated. Epidemiological data, autopsy rate, clinical and autopsy diagnoses and their correspondence and the number of, patients with precise final diagnoses were analysed. Therapeutic effort limitation and palliative care were also evaluated as well as if the final result was expected according to the initial disease or clinical condition of the patients. All the variables were prospectively defined at the start of the study period. RESULTS: A total of 253 cases (6.08‰ admissions) were analysed. The two leading causes of death were disorders related to prematurity and low birth weight, and haematology oncology malignant diseases. Most patients (87%) died in an intensive care unit (neonatal or paediatric). During the study period 134 autopsies (53%) were performed, and new clinically significant findings were observed in 12 of these (7.8%) but in only one case the treatment could have possibly modified the prognosis (class I discrepancy). Therapeutic effort limitation and palliative care were implemented in 41.9%. Death was initially expected in 83.9% of cases. An accurate final diagnosis was defined in 92%, and the aetiology of the disease was considered to be identified in 86.4% of all deaths. CONCLUSIONS: Hospital mortality analysis is useful to evaluate the quality of the paediatric care and to detect adverse results that could be corrected. Paediatric autopsy continues to provide clinically significant data for paediatricians and families. Therapeutic effort limitation and palliative care is increasingly applied in paediatric end of life care. The number of infants and children dying without a final aetiological diagnosis is still considerably high.

[Orthotopic liver transplantation in children younger than one year]. / Trasplante hepático en menores de un año.

BACKGROUND: Orthotopic liver transplantation (OLT) in children younger than one year is associated to higher waiting list mortality and alternative graft sources are required. We present our experience with this particular group of age. METHODS: Infants younger than one year who received an OLT between 1986 and 2005 were reviewed focused on graft and children survival depending on period and type of graft. Periods were 1:1986-1995; 2:1996-2000 and 3:2001-2005. We also evaluate cold ischemia time (CIT), graft lost causes and differences between CIT and anhepatic time (AT) depending on graft type. RESULTS: Eighty-three children received 103 OLT. Liver transplant indications were 59 (72%) biliary atresia, 8 (10%) metabolic causes, 6 (8%) liver failure, 3 (4%) cirrhosis and 7 (6%) miscelaneous. Patient and graft survival after 5 years was increased depending on period: 45% and 65% on period 1, 70% and 80% on period 2, 94% y 97% on period 3 (p < 0.0198). Thirty-seven grafts were reduced lobes (42%); 8 (21%), 17 (45%) and 12 (35%) during periods 1, 2 and 3 respectively and their 5 years survival rate was 68%. Twenty-four were whole grafts (31%); 11 (45%), 10 (45%) and 3 (14%) during periods 1, 2 and 3 and their 5 years survival rate was 63%. Fourteen grafts were living-related donor (16%); 1 (7%), 2 (14%) and 11 (79%) during periods 1, 2 and 3 and their 5 years survival rate was 93%. Eight (11%) were split; 0, 1 (12%) and 7 (90%) during periods 1, 2 and 3 and their 5 years survival rate was 100%. Average CIT depending on graft was: living donor 5,5 hours (IQR: 4-7), split 6,1 hours (IQR: 5-8), whole 9.2 hours (IQR: 6-11) and reduced 8.5 hours (IQR: 6-11) (p < 0.05). Average AT depending on graft was: living donor 1 hour (IQR: 0.5-1.5), split 1 hour (IQR: 0.5-1.4), whole 1,1 hours (IQR: 0.5-1.5) (p > 0.1). Twenty-four grafts were lost (28%): 10 (41%) were surgical related causes and 6/10 (60%) of them were whole grafts. CONCLUSIONS: Survival rates in children younger than one year are similar to another groups of age. There was a significant increase on graft survival according to transplantation group experience. A higher rate of graft lost is associated to whole grafts. Most frequent reasons of graft lose were related to sepsis and immunosuppresion. A significant shortening of CIT is observed in related living donor and split grafts.

Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

Trasplante hepático en menores de un año / Orthotopic liver transplantation in children younger than one year

Introducción. El trasplante hepático (TH) en menores de 1 año es técnicamente difícil, se asocia a mayor mortalidad en lista de espera y necesita técnicas alternativas por la escasez de órganos. Presentamos nuestra experiencia con el TH en este grupo de edad. Material y métodos. Revisamos en las historias de los menores de un año que recibieron un TH entre 1986 y 2005 indicaciones de TH, supervivencia del niño y el injerto según tipo de injerto y etapa (1:1986-1995; 2:1996-2000 y 3:2001-2005), causas de pérdida de injerto y diferencia de tiempo de isquemia fría (TIF) y tiempo de fase anhepática según tipo de injerto. Resultados. Ochenta y tres niños recibieron 103 TH; 59(72%) por atresia de vías biliares, 8(10%) por causas metabólicas, 6(8%) por fallo hepático, 3(4%) por cirrosis y 7(6%) por otras causas. La supervivencia a los 5 años del injerto y del niño aumento significativamente según etapa: 45% y 65% en la etapa 1, 70% y 80% en la etapa 2, 94% y 97% en la etapa 3 (p 0,1). Se perdieron 24 (28%) injertos: 10 (41%) por causas relacionadas con la cirugía y 6/10(60%) en higados enteros. Catorce injertos (58%) se perdieron por razones no relacionadas con la cirugía en forma de rechazo o sepsis. La tasa de retrasplante fue 9/20 (45%) con 1´6 injertos por niño, 7/30 (23%) con 1,2 injertos por niño, 2/33 (6%) con 1´06 injertos por niño en las etapas 1,2 y 3. Conclusiones. El TH en menores de 1 año obtiene resultados iguales o mejores que en otros grupos de edad. Existe un aumento de la supervivencia del injerto y del paciente así como una menor tasa de retrasplante con la experiencia del grupo. Hay más pérdidas del injerto relacionadas con la cirugía en hígados enteros. Las razones mas frecuentes de pérdidas del injerto estuvieron relacionadas con sepsis e inmunosupresión. El TIF es significativamente menor en injertos de donante vivo y Split (AU)

Background. Orthotopic liver transplantation (OLT) in children younger than one year is associated to higher waiting list mortality and alternative graft sources are required. We present our experience with this particular group of age. Methods. Infants younger than one year who received an OLT between 1986 and 2005 were reviewed focused on graft and children survival depending on period and type of graft. Periods were 1:1986-1995; 2:1996- 2000 and 3:2001-2005. We also evaluate cold ischemia time (CIT), graft lost causes and differences between CIT and anhepatic time (AT) depending on graft type. Results. Eighty-three children received 103 OLT. Liver transplant indications were 59 (72%) biliary atresia, 8 (10%) metabolic causes, 6 (8%) liver failure, 3 (4%) cirrhosis and 7 (6%) miscelaneous. Patient and graft survival after 5 years was increased depending on period: 45% and 65% on period 1, 70% and 80% on period 2, 94% y 97% on period 3 (p 0,1). Twenty-four grafts were lost (28%): 10(41%) were surgical related causes and 6/10 (60%) of them were whole grafts. Conclusions. Survival rates in children younger than one year are similar to another groups of age. There was a significant increase on graft survival according to transplantation group experience. A higher rate of graft lost is associated to whole grafts. Most frequent reasons of graft lose were related to sepsis and immunosuppresion. A significant shortening of CIT is observed in related living donor and split grafts (AU)

Shunt porto cava congénito. Malformación de Abernethy / Congenital portosystemic shunt. The abernethy malformation

Introducción. El shunt portosistémico congénito (SPSC) es una patología muy poco frecuente, descrita por primera vez en 1793 por John Abernethy. Existen dos tipos de SPSC: tipo I (shunt termino-lateral) en el que existe ausencia total de flujo portal intrahepático y tipo II (shunt laterolateral) con flujo portal parcialmente conservado. Los SPSC tipo I se presentan predominantemente en el sexo femenino y se asocian con múltiples malformaciones como poliesplenia, malrotación y cardiopatía. Los tipo II, aún más raros, afectan a ambos sexos y no suelen presentar malformaciones asociadas. La encefalopatía hepática es una complicación posible en ambos tipos de SPSC en la edad adulta. El trasplante hepático es el único tratamiento descrito para el SPSC tipo I cuando se vuelve sintomático, mientras que la ligadura del shunt es una opción quirúrgica para el tipo II. Objetivo. Analizar nuestra experiencia en el diagnóstico y manejo de pacientes con esta malformación. Material y métodos. Presentamos cuatro casos de SPSC, tres tipo I y uno tipo II, diagnosticados en nuestro servicio entre enero de 1997 y marzo de 2005. Resultados. De los cuatro casos que presentamos, 3 son varones y 1 mujer, diagnosticados entre los 0 y 28 meses de edad. Tres casos de SPSC son tipo I, 2 varones y una mujer que fue diagnosticada prenatalmente en la semana 12 de gestación. El único paciente con shunt tipo II es varón. La sintomatología inicial en los 2 chicos con SPSC tipo I fue esplenomegalia e hiperesplenismo, con desarrollo ponderoestatural normal. Ninguno presentó cardiopatía. Uno de ellos tiene retraso psicomotor leve, rasgos dismórficos y telangiectasias faciales. Éste presenta una coagulación normal con disfunción hepática crónica (transaminasas elevadas) y nódulos de regeneración en las pruebas de imagen, mientras que el segundo presenta hipoprotrombinemia con tendencia al sangrado capilar (hematomas y epistaxis) con función hepática conservada. Ambos han desarrollado hipertensión portal leve y presentan signos de esteatosis en la biopsia hepática. En el caso femenino tipo I tiene cardiopatía asociada, una comunicación interauricular y desarrollo de ictericia neonatal fisiológica. Su estudio de función hepática es normal, pero en la ecografía se observan calcificaciones intrahepáticas. El paciente con SPSC tipo II tiene además un hipospadias y no presenta clínica relacionada con la malformación portal. En los cuatro casos el diagnóstico fue sugerido por ecografía convencional y Doppler, y confirmado por angiorresonancia magnética. Todos los pacientes siguen un estrecho control clínico y radiológico, sin que hasta el momento hayan precisado tratamiento quirúrgico del shunt o trasplante hepático. Conclusiones. El diagnóstico de este tipo de malformaciones se realiza a veces de forma accidental, aunque hay que tenerlo presente en niños con hepatopatías inespecíficas. La angiorresonancia magnética es el mejor método para el diagnóstico. Se debe realizar seguimiento de estos pacientes debido al riesgo de encefalopatía hepática y la posible morbimortalidad asociada a la hipertensión portal, aunque la cirugía no se indica habitualmente hasta la edad adulta (AU)

Background. Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. Objective. To analyse our experience in diagnosis and management of portosystemic shunts. Methods. We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between january-1997 and march-2005 in our department. Results. We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type I boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound.Type II child associates hypospadias but he has no clinical sign or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. Conclusions. Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis method for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood (AU)

[Congenital portosystemic shunt. The Abernethy malformation]. / Shunt porto cava congénito. Malformación de Abernethy.

BACKGROUND: Congenital portosystemic shunt (CEPS) is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. OBJECTIVE: To analyse our experience in diagnosis and management of portosystemic shunts. METHODS: We report 4 cases of CEPS (3 type I and 1 type II) diagnosed between January-1997 and March-2005 in our department. RESULTS: We present 4 patients with ages at diagnosis ranging from 0 to 28 months, 3 type I CEPS (2 boys and 1 girl) and 1 boy type II. The type I girl was prenatally diagnosed at 12 weeks of gestation. Initial clinical signs in type 1 boys were splenomegaly and hypersplenism, both with normal pondo-statural growth. No polysplenia or cardiac anomalies were assessed. One of them presented mild developmental delay, dismorphic features and facial telangiectasias. He had normal coagulation tests with chronic hepatic dysfunction (high transaminases) and regenerative nodular lesions were seen by imaging techniques. The other type I patient had hypoprothrombinemia, tendency to capillary bleeding (haematomas and epistaxis) with preserved liver function. Both patients have developed mild portal hypertension and present steatosis signs at liver biopsy. The type I girl presents a 21 trisomy and associates a cardiac anomaly (interauricular communication). Her hepatic function test are normal but liver calcifications can be seen by ultrasound. Type II child associates hypospadias but he has no clinical sigh or symptom related to the shunt. In our three cases diagnosis was suggested by conventional and Doppler ultrasound and confirmed by angio-resonance imaging. All our patients are included in a meticulous clinical and radiological follow-up with no need of surgical treatment for the shunt until now. CONCLUSIONS: Although diagnosis of these malformations could be casual we have to think about CEPS in children presenting unspecific liver disease. Magnetic angio-resonance imaging is actually the best diagnosis methods for CEPS. These patients have a high risk for developing hepatic encephalopathy and portal hypertension, so a careful follow-up is required although surgery is not usually needed until adulthood.

Trasplante hepático pediátrico / Pediatric liver transplantation

No disponible

[Childhood cholestasis and bile transporters]. / Colestasis infantil y transportadores biliares.

Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults.

[Pediatric liver transplantation]. / Trasplante hepático pediátrico.

There are no differences in results between pediatric liver transplantation and liver transplantation in adults. The reverts of the liver disease prior to transplantation (particularly the need of intensive care is the best predictor of perspective mortality. Therefore, liver transplantation in children should be indicated prior a severe decompensation of the disease.

Colestasis infantil y transportadores biliares / Childhood cholestasis and bile transporters

La identificación de los sistemas de transporte involucrados en la secreción de la bilis y de los genes que los codifican ha permitido conocer la etiología en la mayoría de los niños afectos de colestasis intrahepática familiar. Las mutaciones en ATP8B1 ocasionan un defecto de FIC1, una flipasa de aminofosfolípidos, y causan un espectro de enfermedad variable, desde colestasis intrahepática progresiva a colestasis benigna recurrente, debido a alteraciones en la composición lipídica de las membranas y a una expresión disminuida del factor nuclear FXR. Las mutaciones en ABCB11 originan el defecto de la bomba canalicular de sales biliares BSEP, con manifestaciones clínicas tempranas y evolución a insuficiencia hepatocelular en la infancia. Las mutaciones en ABCB4 causan una alteración en el transportador de fosfolípido a bilis MDR3, y un espectro de enfermedad variable, con daño ductal progresivo a cirrosis en niños, o con litiasis biliar, colestasis gravídica o cirrosis tardía en adultos

Identification of the transport systems involved in bile secretion and of the genes codifying these systems has allowed the etiology of familial intrahepatic cholestasis to be determined in most affected children. Mutations in ATP8B1 cause a defect in FIC1, an aminophospholipid flipase, and give rise to a variable spectrum of disease, ranging from progressive intrahepatic cholestasis to benign recurrent cholestasis, due to alterations in the lipid composition of the membranes and decreased expression of the nuclear factor FXR. Mutations in ABCB11 cause a defect of the canalicular bile salt export pump (BSEP), with early clinical manifestations and progression to hepatocellular failure in childhood. Mutations in ABCB4 cause an alteration in the MDR3 phospholipid transporter, and a variable spectrum of disease from progressive ductal injury to cirrhosis in children, and gallstones, cholestasis of pregnancy, or late cirrhosis in adults

Comparative study between living and cadaveric donors in pediatric liver transplantation.

UNLABELLED: We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). MATERIAL AND METHODS: The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment (n = 22), left lobe (n = 3), and right lobe (n = 2). In the CDLT group, the grafts were split in situ (n = 10), hepatic reduction (n = 9) and whole liver (n = 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes >2000 U/L), surgical complications, rejection, and resource consumption. RESULTS: Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT (P = NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (P = NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P = .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT (P < .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. CONCLUSIONS: The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.

Intestinal transplantation in children: differences between isolated intestinal and composite grafts.

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.

[The multifocal hepatic hemangioendothelioma. Is always a benign tumor?]. / Hemangioendotelioma multifocal hepático infantil. Es siempre un tumor benigno?

UNLABELLED: The hepatic multicentric haemangioma is defined by its extension, affecting all the mass of the liver. The high mortality associated with it is mostly related with the complications produced by its enormous size (haemodynamic, platelet trapping, spontaneous rupture and bleeding). There is a general belief that is a benign tumor with possibility of spontaneous regression and cure. AIM: Retrospective analysis of our recent cases of MHH with the purpose of: 1 degrees) To show the evolution and results. 2 degrees) To realize if the "benign character" of the tumor is real or if some cases may be considered as malignant tumors. MATERIAL AND METHODS: 10 cases of MHH treated in the last 10 years. In 9 the age of presentation was less than 6 months and one patient was diagnosed at 3 and half years. The diagnosis was confirmed by image techniques in 7 cases and by biopsy in 3. In 7 patients extrahepatic vascular lesions were associated prior to the treatment. Methylprednisolone was given to all the cases and alpha-2-interferon was administered to the patients that not responded to the steroids. Vincristine was added to 2 patients. In two cases the hepatic artery embolization was tried and one patient had a liver transplant. RESULTS: Four children had at least one episode of congestive cardiac insufficiency, two patients suffered a consumption coagulopathy (Kasabach Merrit syndrome), and one presented acute hepatic failure. In six children it has been complete regression of the tumor, one more is still under treatment and three died. The dead were produced by the malignant behavior of the tumor in one case (tumoral rupture of a MHH recurrence in the transplanted liver), and possibly in other (intracranial haemorrhage and hepatic failure in a liver transplantation candidate without demonstrated extrahepatic extension in the previous studies, but with multiorgan dissemination at autopsy. In both cases it was impossible to discover signs of histologic or biologic malignancy neither in the primitive lesion nor in the metastasis. CONCLUSIONS: 1a) The regression of the MHH, spontaneous or induced by the treatment is frequent. 2a) Some cases of MHH are aggressive and develop local recurrences and distant metastasis. 3a) The discrimination between MHH of "benign" or "malignant" behaviour is not possible. 4a) Despite of the unpredictable biological conduct of the tumor, the liver transplantation must be considered as an option in the symptomatic cases that not respond to the conventional treatment.

[Prognostic factors in pediatric liver transplantation. Multivariate analysis]. / Factores pronósticos del trasplante hepático pediátrico. Análisis multivariante.

AIM: To analyze independent risk factors associated with poor graft and patient survival in a series of 292 pediatric liver transplants (PLT) performed in 234 children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and patient survival analysis in 45 variables related to pretransplant patient status, surgical technique and donor conditions. 2. Variables found with univariate analysis to be associated with outcome were entered into a stepwise backward proportional hazard model (Cox), to determine independent prediction of outcome. RESULTS: 11 variables influence the graft survival: recipient age, z-score recipient height, UNOS status, recipient and donor weight, transplant for immune hepatitis, platelet transfusion during the transplant, blood index > 4 during the surgery, type of arterial reconstruction, retransplantation and era of the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000). Four of those variables are independent in the multivariate analysis: UNOS 1 status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient < 3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and era (OR of first and second versus third era respectively 3.93 and 2.81). The independent variables influencing the patient survival were: children receiving more than one graft children less than 3 years old and transplant era. CONCLUSIONS: Liver transplant in small children is associated with an increased risk of graft loss and patient dead. The experience of the hospital in pediatric liver transplantation improves the results, particularly in small children.

Pediatric living donor liver transplantation.

AIM: The aim of this study was to analyze the results of living donor in a pediatric liver transplantation program. PATIENTS: Twenty-six living donor liver transplantations were performed in children from 0.5 to 14.8 years of age. The main indication was biliary atresia (72%) followed by tumors (2 hepatoblastomas and 1 hepatocarcinoma). Left lateral segments were used in 23 (1 transformed into a monosegment), 1 left lobe was used in 1, and right lobes were used in 2. Arterial reconstruction employed saphenous venous grafts in the first 3 cases and end-to-end anastomoses with a microsurgical technique in the following 22 cases. RESULTS: There has been no major morbidity in the donors, with a median hospitalization of 6 days. Four grafts have been lost; 2 in the first 3 cases. In only 1 case, the graft loss was related to the procedure saphenous venous graft thrombosis). Early biliary complications were frequent (23%). Six month, 1 year, and 5 year graft and patient survival rates were 91%, 85%, and 85% and 100%, 96%, and 96%, respectively. CONCLUSIONS: Living donor liver transplantation is an excellent option for transplantation in children.

Hipertensión portal prehepática como complicación tardía del trasplante hepático pediátrico / Prehepatic portal hypertension after pediatric liver transplantion

Algunos niños sometidos a trasplante hepático (TH) desarrollan a largo plazo hipertensión portal prehepática (HPP) y plantean problemas hasta ahora poco conocidos; muchas de las lecciones aprendidas con el manejo de estos enfermad pueden tener además aplicación fuera del trasplante. Objetivos: 1. Analizar la incidencia y factores de riesgo de HPP tras TH. 2, Valorar los resultados con los diferentes tratamientos utilizados. Material y métodos. Estudio retrospectivo sobre 164 niños que sobrevivieron más de un año tras TH. Análisis univariante de posibles factores de riesgo asociados a multivariante (regresión logística) para aquéllos que en el análisis univariante tuvieron significación. Se analizan otros factores asociados y las indicaciones y resultados de dos tipos de tratamiento: dilatación neumática percutánea y shunt quirúrgico (esplenorrenal y meso-portal o shunt de Rex). Resultados. Nueve niños desarrollaron Hpp sintomática (hemorrágica en 8, ascitis en 1), asociada en 2 a trastorno linfoproliferativo postrasplante y a estenosis biliar anastomótica en uno. La edad al primer trasplante (menores de un año), peso (menores de 10 Kg) y necesidad de retrasplante fueron en el análisis univariante las variables asociadas con riesgo incrementado de HPP. Fueron casi significativas el diagnóstico (atresia biliar), y el grado de urgencia del TH. En el análisis multivariante, la necesidad de retrasplantes es la única variable independiente que incrementa el riesgo (riesgo relativo; 4,5 intervalo de confianza 95 por ciento: 1,29-18,87). Al diagnóstico, tres caos mostraron estenosis portal, y ausencia de permeabilidad con trasformación cavernomatosa de la porta en cinco. La hPP fue ocasionada en un caso por desconexión de vena esplénica ( que de momento no requiere tratamiento); los tres casos de estenosis portal fueron dilatados con éxito por abordaje percutáneo, y los dos de los 5 casos de trombosis portal han sido derivados quirúrgicamente; uno mediante shunt esplenorrenal y otro mediante shunt de Rex (primer caso realizado en España); los restantes tres casos están estables y pendientes de solución quirúrgica. La función hepática es normal en los 9 casos. Conclusiones. La HPP puede complicar a largo plazo en pronóstico del TH pediátrico. Diagnosticada en fase de estenosis portal, la dilatación neumática es el tratamiento de elección, debiendo ser tratados los restantes quirúrgicamente. En estos casos, el shunt más fisiológico y la mejor opción es el de Rex (AU)