Liver transplantation for biliary atresia

Orthotopic liver transplantation was performed 15 months to 20 years ago in 126 recipients, all of whom were under 18 years of age. Eighty-six of these pediatric recipients were treated before 1980 with azathioprine (or eyclophosphamide) and prednisone, to which antilymphocyte globulin (ALG) usually was added. One-year patient survival was 40%. In the last 40 cases, the new drug cyclosporine has been given with low doses of steroids. The one-year patient survival increased to 65%. Both in the pre-cyclosporine era and more recently, the survival of patients with biliary atresia has been lower than in the next largest category of patients, namely, those with liver-based inborn metabolic errors. The difficulty of operation in patients with biliary atresia has been greater than in recipients with other diagnoses, partly because of previous operations such as portoenterostomy (Kasai procedure). Hepatic portoenterostomy, worthwhile as it is, has posed technical difficulties for eventual liver transplantation, particularly when complicated Roux limb techniques or venting procedures have been applied. In our total experience the longest survival after liver replacement in a child whose original diagnosis was biliary atresia is 132/3 years.

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Resumen El transplante ortotópico de hígado fue realizado en 126 recipientes con edades menores de 18 años, en el período comprendido entre los pasados 15 meses a 20 años. Ochenta y seis de estos recipientes pediátricos fueron tratados con anterioridad a 1980 con azatioprina (o ciclofosfamida) y prednisona, a lo cual generalmente se añadió globulina antilinfocítica (ALG). La supervivencia a un año fue de 40%. En los Últimos 40 casos se ha administrado la nueva droga ciclosporina, junto con dosis bajas de esteroides. La supervivencia a un año aumentó a 65%. Tanto en la era preciclosporina como en la época reciente, la supervivencia de los pacientes con atresia biliar ha sido más baja que la de los pacientes de la siguiente categoría mayor, constituída por aquellos con defectos metabólicos congénitos del hígado. La dificultad operatoria en los pacientes con atresia biliar ha sido mayor que en los pacientes con otros diagnósticos, en parte debido a operaciones previas tales como portoenterostomías (procedimiento de Kasai). La portoenterostomía hepática, siendo un procedimiento valioso, ha presentado dificultades en cuanto a un transplante hepático eventual, especialmente cuando se han empleado técnicas de anastomosis de Roux-en-Y o procedimientos de descompresión. La supervivencia más prolongada después del reemplazo hepático en nuestra experiencia es de casi 14 años, en un niño cuyo diagnóstico original era atresia biliar.

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Résumé La transplantation orthotopique du foie a été pratiquée (depuis 25 ans jusqu'à 15 mois) chez 126 sujets âgés de moins de 18 ans. Quatre-vingt-six de ces sujets jeunes ont été traités avant 1980 par l'azathioprine (ou cyclophosphamide) et la prednisone ainsi que généralement par la globuline antilymphocytaire. La survie à un an fut de 40%. Dans les 40 dernières transplantations un nouvel agent, la cyclosporine, fut employé simultanément avec de faibles doses de stéroÏdes. Le taux de survie à un an s'est élevé jusqu'à 65%.Aussi bien au cours de la première période que lors de la seconde, le taux de survie des enfants qui ont subi une transplantation pour atrésie biliaire a été inférieur à celui de ceux qui ont été l'objet d'une transplantation pour des affections métaboliques hépatiques du nouveau-né. La difficulté de l'opération chez les sujets atteints d'atrésie biliaire résulte du fait que la transplantation est effectuée très souvent après échec de la porto-entérostomie ou opération de Kasai, de la présence d'une anse jéjunale montée en Y ou d'un ventousage. Le meilleur résultat des transplantations hépatiques pour atrésie biliaire que nous avons pratiquées répond à une survie de 13 ans et 8 mois.

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Supported by research grants from the Veterans Administration; and the National Institutes of Health Bethesda, grant AM-29961.     

Liver transplantation for biliary atresia associated with malignant hepatic tumors

The authors report 3 cases of liver transplantations in children between 4 and 10 years of age, complicated with malignant hepatic tumors after biliary atresia. The preoperative abdominal computed tomography (CT) scans of all 3 cases showed hepatic masses. The serum alpha-fetoprotein levels were elevated highly in 2 cases. After living-related liver transplantation (LRLT), the pathologic findings of the masses in the resected livers showed hepatocellular carcinoma in 2 cases and hepatoblastoma in the other. All cases were associated with biliary cirrhosis. The stage of the liver tumor in the 3 cases using the TNM system was IVA (T4, N0, M0), II (T2, N0, M0) and IVA (T4, N0, M0). Chemotherapy was used in all cases after liver transplantation, and all patients survived with no recurrence. The results suggest that even though malignant liver tumors rarely are complicated with biliary atresia in childhood, one should be alert to the occurrence of hepatic malignancy and perform routine screening of alpha-fetoprotein levels, abdominal CT scans, and magnetic resonance imagings.     

Liver transplantation and the Kasai operation in biliary atresia

To assess the respective morbidity of the Kasai operation and liver transplantation in treating biliary atresia from the perspective of the referring institution, we analyzed the clinical course of 43 consecutive patients hospitalized at our institution from October 1980 to December 1985. Morbidity was arbitrarily defined as complications that required hospitalization, cholangitis, rejection, and was calculated by dividing the actual days hospitalized by the days "at risk." Morbidity assigned to transplantation also included pretransplant hospitalizations necessitated for life-sustaining treatment after referral. The morbidity in 40 patients who were treated by the Kasai procedure was 16.1%, which could be broken down to 50.6% in those who died after operation, 17.4% in those patients subsequently referred for transplantation, and 10.2% in the 16 patients successfully treated. Thirteen of the latter have perfect or near perfect liver function and are in excellent health. The morbidity of the 17 patients who were referred for liver transplantation, including two referred immediately after initial exploration, was 16.0%, which could be broken down to 10.4% before transplantation and 49.8% afterwards. Seven patients died awaiting transplantation, all but one of whom were referred during the first year of life. The average time spent on the waiting list was 203 days. Biliary atresia remains a disease of high morbidity regardless of treatment. Continued hospitalizations are necessary for ongoing Kasai management and life-sustaining treatment following transplant referral. The time spent on transplant waiting lists is protracted, and many patients die before obtaining a new liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver transplantation in children with biliary atresia and vascular anomalies

Eight of 29 infants and children undergoing orthotopic liver transplantation for extrahepatic biliary atresia had associated major vascular anomalies. A distinctive and highly unusual vascular malformation consisting of absent inferior vena cava, anomalous origin of the hepatic artery, and preduodenal portal vein was encountered in three of these children. Although at times technically difficult, single anomalies of hepatic vasculature were satisfactorily handled. In contrast, transplantation attempts were lethal in all three infants having the complex vascular malformation. The suggestion is made that this specific subgroup of patients with biliary atresia be identified in advance and that, at the moment, children with this composite anomaly are highly questionable candidates for liver transplantation.     

Liver transplantation in children with biliary atresia and polysplenia syndrome

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in children. The polysplenia syndrome anomalies, which occur in approximately 10% of children with biliary atresia, may represent special difficulties at liver transplantation. We have reviewed our experience with this syndrome in 116 children with biliary atresia who underwent liver transplantation between March 1984 and December 1989. The main features of the polysplenia syndrome, which included absence of the inferior vena cava, preduodenal portal vein, midgut malrotation, aberrant hepatic artery, and situs inversus, were encountered in 12 of the 116 children (10.3%). Severe portal vein hypoplasia (3.5 mm or smaller) was also present in 7 of these children. Eight patients received a complete and four received a reduced liver graft. The vascular anomalies increased the technical difficulty of OLT but could be surmounted, although they did contribute to the peroperative death of one child. The 1-month survival rate was 83% for the 12 children with features of the polysplenia syndrome and 88% for the other 92 children with biliary atresia alone.     

Orthotopic liver transplantation for biliary atresia

Biliary atresia (BA) represents the most frequent indication for liver transplantation (OLTX) in the pediatric population. The aim of this paper was to present a series collected over the last 7 years from October 1997 through July 2004, including 260 pediatric OLTX in 231 patients. BA was the indication in 137 patients. There were 69 boys and 68 girls of mean weight 10.68 kg and median age 0.9 years. As a primary transplant, 99 patients received a LLS graft; 27 a whole graft; four a I+IV-VIII segment, and two a I-IV segment. Mean follow up was 1047 days (range, 1-2496 day). Infections were diagnosed in 45 patients, vascular complications in 27 patients. Surgical complications that required reintervention occurred in 25 patients. In 41 cases biliary complications occurred, 11 requiring reintervention. 16 patients were retransplanted. In two cases another re-OLTx was performed. Currently 126 patients are alive, showing an actuarial 1 year survival of 92% and 5 year 91%, with actuarial graft survivals of 85% at 1 year and 82% at 3 and 5 years. Our results confirm the effectiveness of OLTx for the treatment of children with BA and a failed Kasai procedure. Split liver grafts represent an excellent organ supply for these patients, achieving optimal results with no mortality on the waiting list.     

Liver transplantation for biliary atresia with special reference to the Japanese children who received liver transplantation in foreign countries

Seven cases out of 8 Japanese children who received orthotopic liver transplantation (OLT) in foreign countries because of biliary atresia as of Oct 1988 are reported. Their clinical courses after OLT have been good. Despite being satisfied with the results, their parents and family feel anxiety such as long term postoperative care and side effects of immunosuppressive therapy. Cost and the handling of rejection or retransplantation were pointed out as the greatest problems related to receiving OLT in foreign countries.     

Portal vein complications after liver transplantation for biliary atresia

The objective of this report is to review portal complications (PC) after pediatric liver transplantation (LT) for biliary atresia (BA) in the Bicetre surgical series. From January 1, 1988, to February 28, 1995, 96 children with BA underwent 115 LTs Portal anastomosis was done on either the recipient portal vein (n = 85) or superior mesenteric vein (n = 11). No antiaggregative agents were administered postoperatively. Median follow-up was 50 months (range, 12 to 97). Nineteen PC (16.5%) occurred in 17 recipients: 16 portal thrombosis (PT) and 3 portal stenosis (PS). Fifteen instances of early PT occurred between days 0 and 17 (median, day 2). Emergency thrombectomy was performed in 9 cases (successful in 5). Three children underwent a secondary portosystemic shunt (successful in 2). Three PS were cured by either surgery or balloon dilatation. Four children died, 3 are alive with portal hypertension (PHT), and 10 are alive without PHT. Three- year patient actuarial survival is 82.4% in PC cases and 82% in others (NS). Significant risk factors of PC are young age and weight at the time of LT, small portal vein, and emergency LT. Analysis of our own results and review of the literature suggest that prevention of PC depends primarily on appropriate surgical technique. Reduction of postoperative hypercoagulability may also play an important role: a meta-analysis of 1,257 published pediatric LT show an overall risk of PT of 2.2% in teams using aspirin with or without dipyridamole compared with 7.8% when no antiaggregative agents are given (P = .0001). (Liver Transpl Surg 1997 Jul;3(4):351-8)     

Surgical limitation for biliary atresia: indication for liver transplantation

Of 245 patients undergoing corrective operations for biliary atresia, jaundice was cleared in 113. In January 1988, 84 of them were living and free of jaundice and the other 19 were alive with jaundice. A vast majority of long-term survivors showed normal growth and development, and were leading normal lives for their respective ages. Portal hypertension, a common late complication, improved spontaneously or after sclerotherapy in jaundice-free patients. Therefore, liver transplantation is not recommended for jaundice-free patients even with esophageal varices. Patients with persistent severe jaundice (serum bilirubin over 10 mg/dL) and those with moderate jaundice (serum bilirubin 5 to 10 mg/dL) and severe esophageal varices require liver transplantation. Patients with moderate jaundice having no or slight varices should be carefully followed. When varices become worse or serum bilirubin rises, liver transplantation is indicated. Patients with mild jaundice (serum bilirubin lower than 5 mg/dL) have a possibility of improvement in their condition before the age of 15 years, and are not recommended for liver transplantation. The high value of the lowest postoperative bilirubin level suggests the necessity of liver transplantation in early childhood. Liver transplantation as the primary treatment for biliary atresia may be indicated only for patients over 120 days of age with an enlarged and hard liver.     

Orthotopic liver transplantation for biliary atresia. Evolution of management

Forty-five patients with biliary atresia were accepted for orthotopic liver transplantation. Nine patients died awaiting transplantation, and 36 underwent transplantation. A portoenterostomy had been performed in 28 of these 36 patients, and its presence did not significantly affect the intraoperative blood loss (5.6 vs 4.1 blood volumes), the need for retransplantation (21% vs 12%), biliary complications (21% vs 12%), postoperative infections (36% vs 25%), or survival (82% vs 63%). These results indicate that early portoenterostomy is appropriate early therapy for biliary atresia; however, prompt referral to a liver transplant center for evaluation at the first sign of cholestasis is needed to attain optimal results for transplantation. Revisions of the portoenterostomy prior to transplantation did not improve the longevity of the procedure but did substantially increase complications and death after orthotopic liver transplantation.     

The influence of portoenterostomy on transplantation for biliary atresia.

After portoenterostomy (PE) for biliary atresia (BA), many patients suffer progressive deterioration of liver function and ultimately require liver transplantation. We retrospectively reviewed a single center's experience with pediatric liver transplantation for BA from 1988 to 2002. Sixty-six patients underwent 69 liver transplants for BA. Forty-two (63%) patients had previously undergone Kasai PE, 11 (17%) biliary appendicoduodenostomy (BAD), and 13 (20%) had no prior biliary drainage (NBD). The BAD procedure offered only short-term biliary drainage--the mean interval between PE and transplant was more than twice that for Kasai patients than for BAD patients (132 versus 49 weeks). The transplants included 11 cadaveric partial, 27 cadaveric whole, and 31 living related transplants. Three patients required retransplant. Prior PE did not increase the incidence of major perioperative complications or unplanned reexploration. After transplant, the 1-, 5-, and 10-year actuarial graft survival rates were 87%, 86%, and 80%, respectively. The 1-, 5-, and 10-year actuarial patient survival rates were 91%, 89%, and 83%. PE remains an important bridge to transplant. In conclusion, transplantation for BA offers excellent long-term graft and patient survival.     

Liver transplantation for deterioration in native liver function after portoenterostomy for biliary atresia in Japan: Short- versus long-term survivors

Purpose

We reviewed our post-Kasai portoenterostomy biliary atresia (BA) patients who required liver transplantation (LTx) for deterioration in native liver (NL) function to investigate mortality in relation to age at LTx.

Parenteral nutrition supplementation in biliary atresia patients listed for liver transplantation

The objective of this study was to determine the impact of parenteral nutrition (PN) on the outcomes of biliary atresia (BA) patients listed for liver transplantation (LT). We retrospectively reviewed the charts of all BA patients at our institution who underwent hepatoportoenterostomy and were listed for LT before the age of 36 months between 1990 and 2010. The initiation of PN was based on clinical indications. Twenty-five PN subjects and 22 non-PN subjects (74% female) were studied. The median PN initiation age was 7.7 months, the mean duration was 86 days, and the mean amount of energy supplied by PN was 77 kcal/kg/day. Before PN, the triceps skinfold thickness (TSF) and the mid-arm circumference (MAC) z scores were decreasing. After PN, TSF (P < 0.001) and MAC (P < 0.001) improved significantly. The PN group had lower MAC and TSF scores than the non-PN group at the time of LT listing. Between listing and LT, MAC and TSF improved in the PN group and worsened in the non-PN groups; as a result, the 2 groups had the same z scores at LT. The PN group had a higher incidence of gastrointestinal bleeding and ascites before LT, but there were no differences in the rates of pre-LT bacteremia, days in the intensive care unit after LT, or patient or graft survival. In conclusion, PN improves the nutritional status of malnourished BA patients awaiting LT, and this is associated with post-LT outcomes comparable to those of patients not requiring PN.     

Preoperative vascular evaluation in living donor liver transplantation for biliary atresia

Background

Liver transplantation is an important treatment option in the management of end-stage liver disease. Preoperative vascular evaluation plays an important role for a safe and successful operation, especially in pediatric patients undergoing living donor liver transplantation (LDLT).

Purpose

The purpose of this study is to assess the usefulness and accuracy of Doppler ultrasound (US), computed tomographic angiography (CTA), and magnetic resonance angiography (MRA) in evaluating vascular anomalies in patients with biliary atresia (BA) undergoing LDLT.

Methods and Materials

Images of Doppler US, CTA, and MRA for preoperative vascular evaluation in 55 patients with BA undergoing LDLT were reviewed with the operative findings.

Results

All patients underwent preoperative US, CTA, and MRA. Pathologic portal vein (n = 18), interruption of the retrohepatic vena cava (n = 1), and aberrant right hepatic artery from the superior mesenteric artery (n = 2) were confirmed during the transplantation. The success rates of CTA and MRA in identifying vascular anomalies were 96% and 82%, respectively (P = .01). The sensitivity, specificity, and accuracy of Doppler US were 89%, 94%, and 92%, respectively. For CTA, it was 94%, 97%, and 96%, respectively; for MRA (including technical failure), it was 75%, 97%, and 89%, respectively.

Conclusion

Doppler US serves as an initial assessment for vascular evaluation and has the advantage in determining vascular flow quantities. CTA and MRA are used for precise surgical planning. However, MRA has lower success and accuracy rates when compared with CTA (P = .01). Doppler US with CTA can provide accurate preoperative vascular imaging in patients with BA undergoing LDLT.