[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)

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)

[Liver transplantation in infants younger than one year of age]. / Trasplante hepático en niños menores de un año.

BACKGROUND: The development of the surgical techniques of hepatic division has maken that the young age (less than one year old) is no longer considered a risk factor in the pediatric liver transplant (TH). AIM: To show our experience with the TH in children younger than one year, comparing these results with the rest of the series and in second place to analyze if a bigger experience improves the results of the TH in this group of patients. METHODS: 44 patients that received a TH with less than a year of age are reviewed. Among them, 27 were in the last five years. The survival indexes of the graft and the patient are determined at 1, 5 and 10 years comparing them with three rest of the series. RESULTS: The grafts and patients survival was slightly inferior in the less than one year old, although in the last five years it improved 71.4% vs 82.1% at one year follow-up, and 61.9 in front of 74.5% at five years. The clinical situation of the patients that were transplanted before the year of life was worse: 43% (UNOS III, IV) in front of 13.1% in the same stadiums in the rest of the serie. In the younger patients, 54% of the grafts were reduced, versus 21% in the older. There were not a higher rate of complications in the young group. CONCLUSIONS: In spite of the difficulties of the TH in children younger than one year of age, the results are not very different from those obtained in the rest of the patients. In these results the experience of the transplant center have a great influence.

[Prognosis in children with biliary atresia successfully treated with Kasai's operation]. / Pronóstico de los niños con atresia biliar tratados con éxito con la operación de Kasai.

BACKGROUND: The Kasai procedure, portoenteroanastomosis (PEA) didn't reach international spreading until the seventy's decade, making difficult to find long-term results from children with ABE successfully treated with this technique. At our institution in the last fifteen years all the therapeutics procedures for these patients can be offered, including the liver transplant. AIM: To show the evolution of our patients with ABE treated with the PEA and that survive long-term without being transplanted. METHODS: The clinical course of 22 patients that survive more than 10 years after the PEA with their own liver is reviewed. The hepatic survival indexes of (success, death or transplant) are beyond the tenth year. The problems raised during the follow-up are analysed. RESULTS: From 99 patients with ABE treated primarily in our center, 22 reached the 10 year-old age after the PEA without a liver transplant. In the follow-up, seven if the these finally needed the transplant. Their median age was 12.2 year-old (range: 10.5-13.8) for a progressive hepatocellular damage in 5 cases associated to syndrome hepatopulmonar in two cases. The other fifteen patients have a compensated hepatopathy. Five of them do not have hyperesplenisme and the serum bilirrubine levels are lower than 1.3 mg/dL. The medium age of these patients at the end of the follow-up was 14.8 years. CONCLUSIONS: In spite of the reestablishment of the biliary flow with the PEA, few are the patients with ABE that preserve their hepatic function lapsed long periods of time. Nevertheless the prognosis of these patients is excellent.

Pronóstico de los niños con atresia biliar tratados con éxito con la operación de Kasai / Prognosis of children with biliary atresia succesfully treated with the Kasai procedure

Introducción. La portoenteroanastomosis (PEA) u operación de Kasai no alcanzó difusión internacional hasta la década de los setenta, por lo que es difícil encontrar resultados a largo plazo de los niños diagnosticados de atresia biliar extrahepática (ABE) tratados con éxito mediante dicha técnica. Asimismo, desde hace quince años en nuestro centro se pueden ofrecer a estos pacientes todas las modalidades terapéuticas incluido el trasplante hepático. Objetivo. Mostrar la evolución de nuestros pacientes con ABE tratados con éxito con la PEA y que sobreviven largo plazo sin ser trasplantados. Material y métodos. Revisamos la evolución de 22 pacientes que sobrevivieron más de 10 años tras la PEA conservando su propio hígado. Determinamos los índices de supervivencia hepática (suceso, muerte o trasplante) más allá del décimo año. Analizamos los problemas que se plantean en su seguimiento. Resultados. De 99 pacientes con ABE tratados primariamente en nuestro centro, 22 alcanzaron la edad de 10 años tras la PEA sin precisar un trasplante hepático. Siete de ellos durante su seguimiento precisaron un trasplante hepático con una edad media de 12,2 años (rango: 10,513,8) por daño hepatocelular progresivo en cinco casos asociado a síndrome hepatopulmonar en dos. Los quince restantes presentan una hepatopatía compensada, sin hiperesplenismo en cinco casos y cifras de bilirrubina sérica inferiores a 1,3 mg/dL en 11 casos. La edad media de estos pacientes en el momento final del seguimiento era de 14,8 años. Conclusiones. A pesar del restablecimiento del flujo biliar con la PEA, pocos son los pacientes con ABE que preservan su función hepática transcurridos largos períodos de tiempo. Sin embargo, el pronóstico de estos pacientes es excelente. (AU)

[Pre-hepatic portal hypertension as a late complication of liver transplantation in children]. / Hipertensión portal prehepática como complicación tardía del trasplante hepático pediátrico.

UNLABELLED: In the long-term after liver transplantation (LT), some children develop prehepatic portal hypertension (PPH) and raise problems not very well known yet; many of the lessons learned with the management of these patients may be useful outside the LT. AIM: 1. To analyze the incidence and risk factors of PPH after LT. 2. To evaluate the results with the different treatments used. METHODS: Retrospective study over 164 children surviving more than 1 year after LT. Univariant analysis of possible risk factors associated and multivariant (logistic regression), for those that had significance in the univariant analysis. Other factors associated are analyzed as well as the indications and results of two types of treatment: percutaneous pneumatic dilatation and surgical shunt (splenorenal and Rex shunt). RESULTS: 9 children developed symptomatic PPH (hemorrhage in 8, ascites in 1), associated to lymphoproliferative post-LT disease in 2, and to anastomotic biliary stricture in 1. The age at first LT (children under 1 year old), weight (below 10 kg), and need of retransplantation (reLT) were in the univariant analysis the associated variables with increased risk of PPH. The diagnosis (biliary atresia) and the emergency status of the LT were almost significative. In the multivariant analysis, the need of reLT is the only independent variable that increases the risk (relative risk: 4.5, confidence interval 95%: 1.29-18.87). At diagnosis 3 cases showed portal estenosis, and 5 showed absence of permeability with cavernomatous transformation. The PPH was caused in one case because of the esplenic vein disconnection (treatment not required at the moment); the three cases of portal estenosis were dilated percutaneously with success, and 2 of the 5 cases with portal thrombosis have been surgically shunted: one by an splenorenal shunt and the other by a Rex shunt (first case done in Spain); the other 3 cases are stable waiting for a surgical solution. The hepatic function is normal in the 9 cases. CONCLUSIONS: The PPH can complicate the prognostic of the pediatric LT in the long term. The treatment depends on the permeability of the portal trunk. Whenever possible, percutaneous dilatation should be attempted; should surgery be required, the Rex shunt is the best option.

La operación de Kasai en la era del trasplante hepático. ¿Técnica curativa o sólo paliativa? / Kasai's operation in liver transplantation era. Curative teciinique or only paliative?

La evolución de niños con atresia de vías biliares (AB) que restablecen el flujo biliar tras la operación de Kasai, pero que desarrollan a largo plazo fallo hepático, confirma el concepto actual de la AB como proceso panhepático y plantea la cuestión de si la operación de Kasai es curativa o sólo paliativa.Objetivos.1. Valorar la eficacia de la portoenteroanastomosis (PEA) en el tratamiento de la AB. 2. Analizar el papel de la PEA en la era actual del trasplante hepático (TH).Material y métodos. De una serie de 148 casos de AB se han seleccionado aquéllos tratados exclusivamente en nuestro hospital desde el diagnóstico (n = 92). Se analizó (Kaplan-Meier) la supervivencia del hígado propio (suceso: muerte o TH) y su relación (logrank) con: sexo, edad a la PEA, tipo anatómico de AB, asociación a síndrome de polisplenia, tamaño de conductillos en porta hepatis, restablecimiento precoz de flujo biliar tras PEA, uso de técnicas de derivación y época (década). Se comparó también la supervivencia de los enfermos (suceso: muerte) entre aquéllos cine tuvieron acceso a TH en caso de necesitarlo (grupo 1, n = 69), y aquéllos que por la fecha de fallecimiento sólo pudieron ser tratados con PEA (grupo 11, n = 23; inicio del programa de TH: enero de 1986).Resultados. Al final del seguimiento 32 niños conservan su hígado original, 22 fallecieron y 38 fueron trasplantados. De 85 niños tratados inicialmente mediante PEA, el restablecimiento del flujo biliar fue completo en 40 (47 por ciento), parcial en 13 (15 por ciento) y nulo en 32 (38 por ciento). A 1, 5, 10 y 20 años, la proporción de niños que conserva el hígado propio es de 91 por ciento, 49 por ciento, 38 por ciento y 21 por ciento, respectivamente, siendo el restablecimiento precoz del flujo biliar el único que se relaciona con un mejor pronóstico (supervivencia del hígado propio a 5, 10 y 20 años, respectivamente, de 89 por ciento, 86 por ciento y 51 por ciento con restablecimiento completo, 58 por ciento, 19 por ciento y 0 por ciento en restablecimiento parcial, y 10 por ciento, 3 por ciento y 0 por ciento en ausencia de flujo, p < 0,001). Son diferentes (p < 0,001) las supervivencias de los enfermos entre los grupos 1 y 11: 92 por ciento vs 74 por ciento a 1 año, 78 por ciento vs 35 por ciento a 5 años, y 76 por ciento vs 30 por ciento a 10 y 20 años, a pesar de ser similares las correspondientes a los hígados originales (76 por ciento, 54 por ciento. 35 por ciento en grupo 1 vs 74 por ciento, 35 por ciento y 30 por ciento en grupo 11, a 1, 5 y 10 años,respectivamente). Conclusiones. El restablecimiento del flujo biliar tras PEA puede conseguirse en centros con experiencia en aproximadamente la mitad de los casos de AB. Aunque a menudo no suponga la curación de la enfermedad, retrasa la indicación de TH y permite conservar el hígado propio durante muchos años con una calidad de vida razonablemente buena. El buen pronóstico actual de la AB se debe al uso combinado y secuencial de la PEA y TH (AU)

Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass.

Familial hypercholesterolemia is the result of mutations in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL). In the homozygous form of the disease (HFHC), cellular LDL receptors either do not form, or, when present, cannot bond LDL and mediate its cellular uptake LDL, and the cholesterol that it transports accumulate in plasma, producing severe premature atherosclerosis and death from coronary artery disease usually before the age of 20. Currently, the only effective treatment is liver transplantation, which, alone or in association with medications, normalizes plasma cholesterol levels. The authors report the cases of 2 siblings with HFHC who underwent portocaval shunt at the ages of 2.5 and 1.5 years, respectively. Portocaval shunt produced an immediate, but insufficient decrease in cholesterol (by 40% and 35%, respectively), leaving them with cholesterol concentrations of about 500 mg/dL. One year later they each underwent ileal bypass without obtaining any significant response. Liver transplantation at the ages of 18 and 16 years, respectively, reduced plasma cholesterol concentrations to 129 and 225 mg/dL, respectively. The earlier operations seriously increased the technical difficulty of liver transplantation and did not produce a favorable effect on the natural course of the disease, so portocaval shunt and ileal bypass are not indicated in HFHC, not even for the purpose of delaying liver transplantation.

Long-term survival expectancy after liver transplantation in children.

PURPOSE: The aim of this study was to assess the long-term survival rate in children who have undergone orthotopic liver transplantation (OLT) in the last 13 years. METHODS: The records of 198 consecutive patients under 18 years of age who underwent 249 OLTs between 1986 and 1998 were reviewed. Actuarial patient survival rates were assessed at 1, 3, 5, and 10 years in the whole series, in the last 5 years, and in patients surviving more than 1 year. Age, weight, and indications were analyzed, as well as type and incidence of posttransplant complications. The median follow-up period was 41 months (0 to 154 months). RESULTS: Biliary atresia was the most common indication (41.9%) followed by alpha-1 antitrypsin deficiency (8.1%), Alagille syndrome (7.6%), and fulminant hepatic failure (6.6%). One hundred forty-six patients (58.6%) were below 5 years, and 46 patients were (18.5%) younger than 1 year at operation. Sixty-eight patients (27.3%) weighed less than 10 kg. One hundred seventy whole organs and 70 reduced, 5 living-related donor, and 4 split-liver allografts were used. Hepatic artery thrombosis (n = 18), primary nonfunction (n = 15), and chronic rejection (n = 14) were the most common causes for allograft failure. Fourteen patients (7%) had posttransplant lymphoproliferative disorders (PTLD) at a median time of 28 months (4 to 124 months) postoperation (3 died). The 1-, 3-, 5-, and 10-year actuarial patient survival rates are 80%, 76%, 74%, and 74%, respectively; over the last 5 years it is 88% at 1 year and 82% at 3 and 5 years. For patients surviving more than 1 year, 3-, 5-, and 10-year actuarial survival rates are 95%, 93%, and 93%, respectively. CONCLUSIONS: (1) Overall results of OLT improve with increasing experience. (2) Children who survive more than 1 year after OLT have an excellent prognosis, although long-term complications of immunosuppression can be expected.

[Kasai operation in the age of liver transplantation. Healing or merely palliative technique?]. / La operación de Kasai en la era del trasplante hepático. Técnica curativa o sólo paliativa?

AIM: To assess the results of portoenteroanastomosis (PEA) and liver transplantation (OLT) in extrahepatic biliary atresia (EHBA). METHODS: Out of a series of 148 EHBA, 92 cases primarily treated by us were selected. Survival with the native liver (end point = death or OLT) and its relationship with the age at PEA, type of EHBA, ductal size and bile flow restablishment were assessed. Patient survival was compared in those patients who had access to OLT when needed (Group I, n = 69) and those in whom only PEA was available (Group II, n = 23). (OLT program started in january 1986). RESULTS: At the end of follow-up, 32 children are alive with their native livers, 22 died and 38 had OLT. 40/85 patients who underwent PEA had complete restablishment of bile flow (47%). The no failure rate (survival of the native liver) at 1, 5, 10 and 20 years, was 91%, 49%, 38% and 21%, respectively. Bile flow restablishment was the only predictor significantly associated with good prognosis (survival of native liver at 5, 10 and 20 years of 89%, 86% and 51%, respectively). Differences in survival were significant (p < 0.001) between patients in groups I and II at 1 year (92% vs 74%), 5 years (78% vs 35%), 10 years (76% vs 30%) and 20 years (76% vs 30%). CONCLUSIONS: Bile flow restablishment after PEA can be obtained in experienced centers in about 50% of cases of EHBA. The combined and sequential use of PEA and OLT allows excellent long-term survival in EHBA.

[Pediatric liver transplantation: now the patients are different and the problems are different as well]. / Trasplante hepático pediátrico: los enfermos son ahora diferentes y los problemas también son distintos.

AIM: 1. To show how in a program of pediatric liver transplantation (PLT) with 12 years of experience, the continuous use of technical innovations has allowed to improve the results and to treat the most complex cases. 2. To point out that when the immediate results of the transplant improve and the evolution time get longer, the late complications become the main source of concern. MATERIAL AND METHODS: The graft survival and the incidence of early surgical complications was compared between the first 100 PLT and the last 100 PLT (Total 235 PLT). The patients survival was also compared between the first and the last 5 years. In every case it was analyzed the age and weight of the children at the time of the transplant and the type of graft (full or reduced liver). The incidence of late complications in the global series was also analyzed, especially the posttransplant lymphoproliferative disease (PTLD) and the late biliary and vascular complications. RESULTS: There are significant differences between the first 100 PLT and the last 100 PLT in relation with the age of the patients (6.8 +/- 0.6 vs 4.2 +/- 0.5 years), the number of children younger than 1 year (4 vs 28), weight (22.4 +/- 1.2 vs 16.9 +/- 1.7 kg), number of PLT in children under 10 kg (7 vs 43), use of reduction techniques (7 vs 49), rate of hepatic artery thrombosis (12% vs 3%), and rate of early biliary complications (13% vs 4%). The 5 years survival of the graft was 51% in the first 100 PLT vs 65% in the last 100 PLT, and the 5 years patients survival was 70.1% in the first 5 years of the program vs 79.6% in the last 5 years. Among the late complications in the global series, 13 cases of PTLD (2 deaths) have special relevance, 6 cases of late anastomotic biliary stricture, 4 cases of portal stenosis, 1 arterial thrombosis, 1 death due to a fulminant sepsis and another death because of a colitis with multiple hepatic abscess. CONCLUSIONS: 1. The result of PLT improve, despite of the fact that in the last years the difficulty of the surgical procedures have increased (the patients are younger, with less weight and the reduction techniques are used more frequently). 2. The late complications have a significant influence in the prognosis, being that influence not completely established yet.

Late biliary complications in pediatric liver transplantation.

PURPOSE: The aim of this study was to review the biliary complications occurring in late follow-up after liver transplantation in children. METHODS: The medical records of 135 children who received orthotopic liver transplantations (OLT) and had graft survival of more than 1 year were reviewed. Technical variants using a reduced-size graft were applied in 32 (23.7%). For biliary reconstruction, 15 patients had choledochocholedochostomy and 120 a Roux-en-Y loop. Biliary reoperation in the early post-OLT period was needed in 24 patients (17.7%). Routine checking of liver function and duplex Doppler ultrasonography (DDS) were performed during the follow-up period, which averaged 58 months. Late biliary complication was defined as that occurring after the first hospital discharge. RESULTS: Late biliary complications occurred in 18 children (13.3%); 16 showed symptoms or analytical disturbances in liver function tests. The Diagnoses included uncomplicated cholangitis (n = 6), anastomotic biliary stricture (n = 7), ischaemic damage of the biliary tree (n = 3) including one late (28 months) hepatic artery thrombosis leading to an intrahepatic biloma. and bile leak after T-tube removal (n = 2). The six children with uncomplicated cholangitis had no repeat episodes in follow-up despite persistent aerobilia. Six patients affected by anastomotic strictures were treated successfully with percutaneous dilatation and, if present, stone removal. Persisting dysfunction and cholangitis occurred in one case affected by ischaemic biliary disease. Biliary leaks after T tube removal settled spontaneously. Risk factors for late biliary complications were determined. There was no relation to the cold ischaemia time, type of graft or biliary reconstruction, or previous early post-OLT biliary reoperation. Aerobilia (affecting 21.5% of OLT patients) was related to cholangitis (P = .001). CONCLUSIONS: Anastomotic strictures, reflux of intestinal contents via the Roux-en-Y loop, and residual ischaemic damage led to late biliary complications in 12% of paediatric OLT patients. Evidence of biliary dilatation on DDS may be delayed in anastomotic strictures; in these cases the results of percutaneous treatment were excellent. Children with aerobilia have and increased risk of cholangitis.

Short-term cyclosporine induces a remission of autoimmune hepatitis in children.

BACKGROUND/AIMS: The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. METHODS: This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded. RESULTS: Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. CONCLUSIONS: Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.