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Background: Alagille syndrome (ALGS) is an autosomal dominant disorder, characterized by a paucity of intrahepatic bile ducts, resulting in significant cholestasis, and peculiar extrahepatic features. Some ALGS patients show a considerable overlap with biliary atresia (BA), and they can undergo Kasai procedure. The purpose of this study is to show the manifestations of BA overlapped ALGS cases in our institution, and to compare the outcomes of ALGS patients following liver transplantation (LT) between those who previously underwent Kasai surgery (ALGS-Kasai group) and those who did not (ALGS-non-Kasai group)., Methods: Medical records of ALGS patients who underwent LT in Kyoto University Hospital, Japan from January 1992 to March 2018 were analyzed. ALGS diagnosis was determined according to physical, radiologic, and histopathological findings., Results: Thirty-one patients were ascertained (ALGS-Kasai: 4 males and 5 females vs. ALGS-non-Kasai: 14 males and 8 females, p = 0.43). Of 31 ALGS patients, 96.8% of children had pulmonary artery stenosis, 54.8% showed facial features, 29% revealed skeletal anomalies and 9.7% demonstrated ocular anomalies. The age at LT was significantly younger in ALGS-Kasai than ALGS-non-Kasai group (1.47 [interquartile range (IQR), 0.75-1.92] vs. 5.1 [IQR, 1.4-9.29] years; p = 0.038). Overall patient survival did not significantly differ between ALGS-Kasai (88.9%) and ALGS-non-Kasai patients (86.4%) (p = 0.84). Furthermore, the 1-year, 5-year, and 10-year patient survival rates for ALGS-Kasai group were 100%, 88.9%, and 88.9%, respectively, whereas those for ALGS-non-Kasai group were 90.9%, 90.9%, and 86.4%, respectively, with p-values of 0.36, 0.90, and 0.84, respectively., Conclusions: BA overlapped ALGS cases had neonatal progressive cholestasis which prompted Kasai procedure, and early liver dysfunction after Kasai led to performing LT. The ALGS-Kasai patients undergo LT at earlier ages than the ALGS-non-Kasai patients, however, overall patients' survival rates are similar between groups. Overall ALGS patients' survival rate after LT is considered high., Levels of Evidence: Level III; Case-control study or Retrospective comparative study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Alagille Syndrome (AGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) are rare pediatric biliary disorders that lead to progressive liver disease. This study reviews our experience with the surgical management of these disorders over the last 20years., Methods: We retrospectively reviewed the records of children diagnosed with AGS or PFIC from January 1996 to December 2016. Data collected included demographics, surgical intervention (liver transplant or biliary diversion), and complications., Results: Of 37 patients identified with these disorders, 17 patients (8 AGS,9 PFIC) underwent surgical intervention. Mean postsurgical follow-up was 6.9±4.7years. Liver transplantation was the most common procedure (n=14). Two patients who were initially thought to have biliary atresia underwent hepatoportoenterostomy, but were subsequently shown to have Alagille syndrome. Biliary diversion procedures were performed in 3 patients (external n=1, internal n=2). PFIC patients tended to be older at the time of liver transplant compared to AGS (4.3±3.9years vs. 2.4±1.1years, p=0.25). The AGS patient with external diversion had resolution of symptoms and no complications (follow-up: 12.5years). Both PFIC patients with internal diversion (conduit between gallbladder and transverse colon) had resolution of pruritus and no progression of liver disease (follow-up: 3.8 and 4.5years)., Conclusions: AGS and PFIC are rare biliary disorders in children which result in pruritus and progressive liver failure. Three patients in this series (8%) benefited from biliary diversion for control of pruritus and have not to date required transplantation for progressive liver disease. 38% underwent transplantation owing to pruritus and severe liver dysfunction., Level of Evidence: 2b., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Progressive familial intrahepatic cholestasis (PFIC) with low gamma-glutamyl transpeptidase (GGT) and Alagille syndrome are associated with persistent cholestasis and severe pruritus. Various types of biliary diversion have been used to reduce this pruritus and prevent liver dysfunction. We report our experience concerning the efficacy and safety of total biliary diversion (TBD) as an additional treatment option., Methods: TBD was performed in four PFIC patients and one patient with Alagille syndrome, and was accomplished by anastomosing a jejunal segment to the choledochal duct terminating as an end stoma, or by disconnecting the choledochal duct after previous cholecystojejunocutaneostomy., Results: TBD resulted in a marked improvement of symptoms and biochemical parameters in all PFIC patients. Despite relief of pruritus, cholestasis persisted in the Alagille patient. During 5-15years of follow-up, no clinical signs of fat malabsorption such as diarrhea or weight loss were encountered. However, to maintain adequate levels of fat-soluble vitamins, especially of vitamin K, substantial supplementation was necessary., Conclusions: Total biliary diversion can be a useful surgical treatment option for patients with low-GGT PFIC and possibly also Alagille syndrome, when partial biliary diversion is insufficient. It can be performed without inducing clinical signs of fat malabsorption although individualized supplementation of fat-soluble vitamins with careful monitoring is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This is a case report of the first patient with Alagille syndrome (AGS) to undergo a partial internal biliary diversion (PIBD) for the treatment of symptoms refractory to medical therapy. Alagille syndrome is a hereditary disease resulting in chronic cholestasis and hypercholesterolemia that can lead to severe and intractable pruritus and disfiguring and debilitating xanthomas. PIBD has proven to be an effective treatment option for other causes of cholestatic liver disease. This report reviews the immediate and 2-year follow-up of a patient after this surgical procedure. The results suggest that PIBD has potential to provide relief of intractable symptoms and improve the quality of life in patients with AGS while avoiding an external stoma. It does not, however, appear to prevent the progression of liver disease. Long-term follow-up is still needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Alagille syndrome (AGS) can result in pruritic self-mutilation and disabling or disfiguring xanthomas. Though external biliary diversion and transplantation have been described for AGS, few data exist for the use of ileal exclusion (IE) in this setting., Methods: Three patients with AGS with symptomatic cholestasis despite maximal medical management underwent IE. In each case, small bowel length was measured and the terminal 15% of ileum was excluded using stapled division and ileocecal anastomosis. Symptom scores were collected after institutional review board approval and are presented here as mean (range). Pruritus and xanthomas were graded as follows: 0 = none, 1 = mild scratching/minimal, 2 = active scratching/moderate, 3 = abrasions/disfiguring, 4 = mutilation/disabling., Results: Mean follow-up was 30 months (4-45 months). Pruritus score decreased from 3.33 (3-4) to 0.33 (0-1). Xanthoma score decreased from 3.67 (3-4) to 1.67 (1-2). All patients were maintained on nutritional supplements pre- and postoperatively without a change in management. No patients experienced diarrhea or dehydration postoperatively. There were no complications., Conclusions: Ileal exclusion effectively decreases refractory pruritus and xanthoma burden in AGS. This procedure offers the advantages of reversibility, avoidance of a stoma, and technical ease. Ileal exclusion should be considered for symptomatic AGS refractory to medical management as an alternative to external biliary diversion or liver transplantation.

Alagille syndrome is characterized by a paucity of bile ducts in the liver. The syndrome is associated with some or all the features of chronic cholestasis, cardiac disease, skeletal abnormalities, ocular defects and a distinctive facial appearance. The most common finding is chronic cholestasis, which causes intractable pruritus, xanthoma, deficiency of certain metabolic nutrients and growth retardation. Cardiac abnormalities are the most common cause of death in these patients. It is unusual to see the clinical picture of hepatic failure resulting in cirrhosis and requiring transplantation, but liver transplantation is indicated in Alagille syndrome patients who have chronic cholestasis. If the disease is diagnosed in childhood, transplantation can improve significantly the patient's prognosis and the quality of life. In recent years, auxiliary liver transplantation has gained popularity for treating both acute and chronic liver disease. Heterotopic segmental liver transplantation is an alternative treatment modality for patients who do not require native liver removal. Individuals with Alagille syndrome are good candidates for this type of treatment. J Pediatr Surg 36:667-671., (Copyright 2001 by W.B. Saunders Company.)

The authors performed a partial biliary diversion on a 10-month-old child with Alagille syndrome using the appendix vermiformis as a conduit between the gallbladder and the abdominal wall skin. Three years later the patient is well, and his previously severe pruritus is controlled. The appendix has a lumen closer to that of the biliary tree, does not accumulate significant amounts of bile, and provides a smaller stoma. The small bowel is undisturbed, and there is less interference with a possible future liver transplant.

Purpose: Pediatric liver transplantation is an accepted therapy for end-stage liver disease, but little long-term data exist., Methods: From October 1984 to October 1994, 202 patients underwent a total of 225 liver transplantations. There were 98 boys and 104 girls, the average age was 5.1 +/- 4.9 (range, 0.2 to 19.1) years. Thirty (16%) were under 1 year of age. The diseases that required transplantation included biliary atresia (BA) (45%), metabolic liver disease (MLD) (9.9%), acute hepatic failure (6.9%), and Alagille's syndrome (AS) (5.4%). Originally the immunosuppression was cyclosporine- and steroid-based; the later regimens also included azathioprine and antilymphocyte preparations. All reported survival rates were derived from life-table analysis., Results: The patient survival rates at 1, 5, and 10 years were 76%, 70%, and 61%; the retransplantation rate was 11%. The respective graft survival rates were 71%, 63%, and 59%. There were 60 deaths; 48 (81%) occurred in the first year. These first-year deaths were from sepsis (20; 42%), central nervous system problems (5; 11%), intraoperative complications (4; 8%), lymphoproliferative disease (LPD) (2; 4%), rejection (2; 4%), primary nonfunction (2; 4%), and miscellaneous other causes (7; 15%). There were 12 deaths after the first year, from LPD (3; 25%), sepsis (1; 8%), rejection (2; 18%), cancer (1; 9%), secondary hepatic failure (1; 9%), cerebral vascular accident (1; 9%), or pre- or postoperative complications (3; 25%). Compared with the overall survival rate, patients with MLD had a better chance of survival (83%; P <.012) than did those with AS (45%; P < .001). The 5- and 10-year survival rates for patients with BA were 61% and 58%. Over the past 2 years, the survival rate has increased (87% v 72%; P < .05) as early septic deaths have decreased (from 2.6 to 1.0 per year)., Conclusion: Liver transplantation is effective treatment for end-stage liver disease. Decreasing the number of early septic deaths has improved the chance of survival, and better diagnosis and treatment of LPD would improve the late survival rate.