The future role of hepatic portoenterostomy as treatment of biliary atresia.

According to our recent study, 38 of 93 patients (40.9%) who underwent portoenterostomy at Juntendo University Hospital between 1977 and 1986 survived for more than 5 years. In order to learn the future improvement of the prognosis of biliary atresia patients who undergo portoenterostomy, we investigated the relationship between the prognosis of biliary atresia patients and the age and the histological changes of liver at the time of surgery. Twenty-seven of 30 patients (90%) who survived for more than 5 years with no jaundice and no findings of liver cirrhosis had a mild degree of liver fibrosis (F1 or F2) and a mild degree of degeneration of intrahepatic bile ducts (B1 or B2) at the time of surgery, in spite of the difference of size of intrahepatic bile ducts at the porta hepatis. On the other hand, all 8 patients who showed severe liver fibrosis (F3) and severe degeneration of intrahepatic bile ducts (B3) did not survive for more than 5 years. Accordingly, we can expect promising prognoses in patients who undergo refined portoenterostomy procedures and receive proper postoperative treatment before they have severe histological changes of liver. The portoenterostomy will still play an important role as treatment of biliary atresia in the future.     

The surgery of biliary atresia

One hundred thirty-one consecutive infants with biliary atresia were operated on during the 15-year period between 1973 and 1988. Six patients did not have biliary reconstruction because of advanced cirrhosis or transplant preference. The other 125 infants had excision of all nonpatent extrahepatic bile ducts; biliary drainage was provided by a gallbladder-common bile duct conduit in 14 patients and by a Roux-en-Y portoenterostomy in 111 infants (including the seven patients with correctable biliary atresia). The bilioenteric conduit was temporarily exteriorized and, for the past 2 years, a conduit intussusception valve was incorporated. Immediate postsurgical bile drainage was achieved in 103 infants (82%). Reoperation during the first 6 postoperative weeks restored bile flow in 14 of 18 infants who had shut down. Seventy-two patients (57%) had sustained (more than 1 year) relief of biliary obstruction. Postoperative morbidity was substantial. The six children not having corrective surgery died within 19 months. Three patients were lost to follow-up. Sixty-eight patients having Kasai's operation died, 55 from complications of liver disease, 1 from a coexisting malformation, and 12 after liver transplantation. Fifty-seven patients are alive, 13 by virtue of liver replacement, 9 with mild-to-moderate hepatic sequelae, and 35 (28%) with normal to near-normal liver function. Although none is considered "cured," the 35 children are anicteric, have normal growth and development, and participate in full school activities (including contact sports). Average follow-up is 85.8 months (range 1 to 15 years).     

Echographic signs of biliary atresia

The assessment of echographic features of biliary atresia was conducted in 65 newborn children ageing up to 3 mo. Their characteristic variants were revealed: the absence or reduction in size of gall-bladder, the presence of hyperechogenic triangular formation in V. portae bifurcation (the symptom of "triangular cicatrix"); the thickening of anterior wall of V. portae right branch. The timely and correct establishment of the diagnosis permits a child to survive and serve the hepatic fibrosis prophylaxis. Echohepatography is a sufficiently trustful method of investigation.     

胆道闭锁诊治体会

目的　分析胆道闭锁诊断、治疗及预后情况 ,探讨胆道闭锁的早期诊断和治疗策略。方法　回顾性分析我院近 5年收治的 2 8例胆道闭锁患儿诊断手段、手术年龄、手术方式及术后生存率。结果　胆道闭锁早期诊断率为 1 4 % (4 / 2 8) ,手术时年龄 1 3～ 2 70d ,6 0d以内 4例 (1 4 % ) ;6 1～ 90d 1 3例 (4 6 % ) ;91～ 1 2 0d 8例 (2 9% ) ;1 2 0d以上 3例 (1 1 % )。没有患儿接受肝移植 ,1～ 5年生存率为35 % (9/ 2 5 )。结论　密切观察临床表现、掌握胆道闭锁的影像学特点和及时采用腹腔镜探查可提高胆道闭锁的早期诊断率。完善手术方式、让更多的患儿接受肝移植、开辟新的治疗方法如抑制肝胆管细胞凋亡、抗体及基因治疗可提高胆道闭锁的长期治愈率     

Corticosteroid therapy in biliary atresia

Sixteen patients with biliary atresia had 44 steroid courses for treatment of cholangitis or diminution of bile flow following Kasai hepatic portoenterostomy operations. A "blast" type (high dose/short duration) steroid administration was employed to potentiate the choleretic and anti-inflammatory effect. There was a significant augmentation of bile flow and a reduction in maximum temperature, serum bilirubin, and alkaline phosphatase.     

Liver transplantation for biliary atresia

Biliary atresia is the most common indication for liver transplantation (OLT) in children. We present our experience with OLT as a treatment for end-stage liver disease in children with biliary atresia. We performed a retrospective review of 20 biliary atresia patients (11 male, 9 female patients; mean age, 21.4 months; range, 6 to 84 months) who had undergone OLT. Mean preoperative weight and height were 10.1 +/- 5.8 kg and 72.5 cm, respectively. Thirteen recipients were younger than 1 year of age, and 15 weighed less than 10 kg at the time of OLT. Fourteen recipients had undergone a Kasai operation prior to the OLT. The mean serum total bilirubin level was 22.56 mg/dL before OLT. Eighteen left lateral segment grafts and two whole grafts were transplanted. The mean recipient operative time was 9.25 hours. The mean recipient intraoperative blood loss was 1.81 U. Two hepatic arterial thromboses and one biliary leak occurred soon after surgery. Portal vein stenoses developed in two recipients at 10 and 12 months after OLT; both were treated with balloon dilatation. Two biliary stenoses, which occurred at 10 months and 3.5 years after surgery, were treated with balloon dilatation. Two recipients died at 2 and 12 days after OLT because of respiratory distress syndrome and sepsis, respectively. The remaining 18 (90%) recipients are alive with good graft function. The overall rejection rate was 31.25%. OLT is an effective treatment for children with biliary atresia and a failed Kasai procedure. Living related liver grafts represented an excellent organ supply for these patients.     

Association of biliary atresia and urogenital sinus

A case of an association of extrahepatic biliary atresia (EHBA) and urogenital sinus (UGS) anomaly that was diagnosed as an urachal remnant antenatally is reported. Diagnostic laparoscopy of the abdominal cavity in the postnatal period was the most helpful step for making the diagnosis. Biliary atresia and urogenital sinus, which was the cause of bladder outlet obstruction, were treated successfully. To the authors' knowledge, this is the first case of this type of association introduced to the literature. J Pediatr Surg 36:635-637.     

Congenital biliary atresia and congenital biliary dilatation in siblings.

Congenital biliary atresia or congenital biliary dilatation in siblings have been reported, although the genetic influences in these diseases are considered to be obscure. We report a case of congenital biliary atresia and congenital biliary dilatation in sisters.     

Maternal microchimerism in biliary atresia

Background

The aim of this study was to determine the existence and extent of maternal microchimerism in the livers of biliary atresia (BA) patients.

Methods

Two series of investigations were performed based on the sex of our subjects. Subjects for series I were men, of which 6 had BA. Livers were analyzed using X and Y chromosome probes and fluorescent in situ hybridization. Subjects for series II were woman. Nine BA cases and their mothers were HLA typed (class I). Daughter livers were also tested for antibodies to maternal and other HLA. Two cases of neonatal hepatitis, 2 cases of Alagille syndrome, and 1 case of Byler syndrome acted as controls.

Results

All male BA livers were found to contain a mixture of cells with 1 and 2 X chromosomes (ie, XY or XX). All livers from male controls had only 1 X chromosome (ie, XY). All female BA subjects had varying intensities of antimaternal HLA class I (HLA-A) antibodies in their bile duct epithelium and hepatocytes (strong, 5; mild, 3; weak, 1). The liver from the female control did not display any antimaternal HLA class I antibodies (HLA-Ab).

Conclusion

Our preliminary data appear to show that maternal microchimerism is present within the livers of patients with progressive postnatal type BA. We suggest that BA could in fact be a graft-vs-host disease masquerading as an autoimmune reaction triggered by maternal microchimerism, and we intend to pursue this hypothesis further to clarify the etiology of BA.     

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.