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BACKGROUND Vitamin D deficiency is highly prevalent in children with intestinal failure (IF) who receive parenteral nutrition (PN), but data on vitamin D status after achieving enteral autonomy (EA) are limited. We aimed to evaluate the prevalence of vitamin D deficiency in this population while exploring clinical variables that may be associated with its development. METHODS A retrospective review was performed on 29 children with IF who had achieved EA. Deficiency was defined as a mean serum 25-hydroxyvitamin D

Due to concerns related primarily to allergic response and malabsorption, enteral nutrition therapy has traditionally relied on the use of elemental formulas in children with intestinal failure (IF). Blended food diets via a gastrostomy tube have been reported to improve feeding tolerance in pediatric populations receiving long-term enteral nutrition therapy. Complex macronutrients have been shown to stimulate intestinal adaptation in animal models. We report on our experience in children with IF who had an overall improvement in stool output when transitioned from an elemental formula to a tube feeding formula with real food ingredients (TFRF). Data were collected in a retrospective chart review of children with IF, >1 year of age, who were receiving enteral nutrition via continuous infusion, bolus feeding, or both. Indications for the TFRF trial were diarrhea or inconsistent stooling patterns. Ten children with a mean small bowel length of 48.3 cm were trialed on TFRF. Nine of 10 (90%) children tolerated the transition to 100% TFRF, of which 7 of 9 (78%) had their entire colon in continuity. The average age at successful transition was 29.2 months, and the average length of time to transition to 100% TFRF was 67.3 days. TFRF is well tolerated in children >1 year of age with IF; it also improves their stooling patterns. A commercially available TFRF is a cost-effective and nutritionally adequate means of providing nutrition to this patient population.

Objectives: Although use of 70% ethanol lock therapy (ELT) has been shown to decrease the rate of catheter-related bloodstream infections (CRBSIs) in patients with intestinal failure and central venous catheters (CVCs), concerns have been raised about its association with higher rates of mechanical problems and CVC replacements (CVC-Rs). We sought to compare the rates of CRBSI, mechanical problems, and CVC-Rs in a cohort of pediatric patients with intestinal failure, with and without ELT (ELT+ and ELT−, respectively). Methods: Data were collected in a retrospective chart review from February 2007 to May 2014. Mann-Whitney and Wilcoxon signed-rank tests were used to compare nonparametric and paired data, respectively. Results: Twenty-nine children had 9033 catheter days (CDs). The ELT+ group (vs ELT−) had lower rate of infection and significantly fewer CVC-Rs due to infection but significantly more mechanical events and related CVC-Rs with significantly shorter mean CVC survival. In 13 children who had a p...

Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations. (Hepatology Communications 2018;2:515-528).

The aim of the study was to assess health-related quality of life (HRQOL) in children with Alagille syndrome (AGS) in comparison with a normative population and other chronic diseases, and also to examine the effect of AGS-specific morbidities on HRQOL.A cross-sectional study was performed using the Child Health Questionnaire Parent Form 50 (CHQ-PF50) to measure HRQOL in patients with AGS. AGS HRQOL was compared with that of a normative population and those previously studied by the CHQ, including juvenile rheumatoid arthritis, attention-deficit/hyperactivity disorder, and liver transplantation. AGS-specific questions were used in multiple regression analysis to determine correlation of features and symptoms of AGS with HRQOL.Seventy-one patients with AGS, ages 5 to 18 years, were studied. Those families completing surveys demonstrated that children with AGS had significantly lower HRQOL (P0.05) compared with the normative sample. In comparison with children with juvenile rheumatoid arthritis, children with AGS had lower psychosocial function scores (P0.0005). In comparison with children with attention-deficit/hyperactivity disorder, children with AGS had lower physical function scores (P0.0005) but higher psychosocial function scores (P0.0005). Children with AGS had lower physical function scores than a liver transplant population (P0.05). Regression analysis indicated that cardiac catheterization or surgery, mental health diagnoses, and poor sleep were associated with lower CHQ scores in children with AGS.In the first descriptive report of HRQOL in a large cohort of patients with AGS, HRQOL was impaired, indicating a significant burden of chronic disease in both physical and psychosocial health. Additional prospective evaluation is needed in multicenter collaboration.

In children, eosinophilic esophagitis (EE) is predominantly, but not exclusively, a food-hypersensitivity disorder. A crystalline amino acid-based elemental diet (ELED) formula currently remains the most effective nutritional treatment in inducing clinical and histologic remission. However, compliance with an exclusive, poor-tasting liquid formulation is difficult.This retrospective observational study assessed the short-term clinical and histologic responses of 2 cohorts of children with EE evaluated during 2 different time periods: one was treated with the standard 6-food elimination diet (SFED) and the other was treated with ELED. Of the 60 children who met the inclusion criteria and were compliant with the dietary protocol, 35 were treated with a diet excluding cow-milk protein, soy, wheat, egg, peanut, and seafood while allowing all other table foods and 25 were treated exclusively with ELED. Repeat esophageal biopsy specimens were obtained at least 6 weeks later.Twenty-six of 35 (74%) in the SFED group and 22 of 25 (88%) in the ELED group achieved significant improvement of esophageal inflammation (/=10 eosinophils/high-power field). The pretreatment and posttreatment peak eosinophil counts for the SFED were 80.2 +/- 44.0 and 13.6 +/- 23.8 (P.0001) and 58.8 +/- 31.9 and 3.7 +/- 6.5 (P.001) for the ELED group, respectively.SFED treatment was associated with clinical and histologic improvement in EE in an observational study. It offers advantages of better acceptance, cost, and compliance than ELED and should be considered as an option in the initial management of children with EE.

Establishing a rapid and accurate diagnosis of the cause of neonatal liver disease is an urgent matter. The initial detection of this condition relies on the sensitivity of the primary care provider or pediatrician to the signs and symptoms of jaundice and abnormal stool and urine color. It is critical to evaluate jaundice in any infant older than 2 weeks with measurement of fractionated bilirubin, and further assessment is necessary if the direct value is above 1.0 mg/dL in the setting of a total bilirubin of less than 5.0 mg/dL or a direct bilirubin of more than 20% of total if the total is more than 5.0 mg/dL. A diagnostic algorithm for the evaluation of infants who meet these criteria can guide physicians in selecting appropriate and timely diagnostic testing and referral to pediatric gastroenterology for these patients, whose outcome will rely on rapid diagnosis.

Objectives: To evaluate the safety, outcomes, and complications of percutaneous liver biopsies (PLB) in infants aged 0 to 3 months. Methods: We retrospectively reviewed the hospital records of all infants less than 3 months old who underwent PLB at Children's Memorial Hospital between July 1, 1997 and June 30, 2004 for complications surrounding the procedure and risk factors that might lead to complications. Results: Sixty-six PLBs were performed in 63 infants. Most patients tolerated the procedure without complications. Twelve complications were recorded, for an overall complication rate of 18%. Of these, five were directly related to the procedure, and seven were sedation related. Three patients experienced a drop in hemoglobin greater than 2 gm/dL, one patient developed a bile leak, and one developed a skin hematoma. Seven patients had respiratory difficulty related to sedation, which manifested as increased work of breathing or decreased respiratory rate with depression in pulse oximetry. Conclusion: We conclude that PLB in young infants is associated with a somewhat higher risk of complications than in older children, particularly complications related to sedation.

The Pediatric End-Stage Liver Disease (PELD) score was designed to reduce subjectivity in liver allocation and to advantage patients with a higher probability of waiting list mortality. The aims of this study were to determine the impact of PELD implementation for children with chronic liver disease and to assess whether PELD met its goal of standardization of liver allocation for children. This study used data reported to the United Network for Organ Sharing (UNOS) registry for children with chronic liver disease receiving primary cadaveric liver transplant between January 2000 and December 2001 (pre-PELD) and March 2002 and July 2003 (PELD). PELD reduced the percentage of children transplanted while in an intensive care unit and as status 1. A calculated PELD score was used for allocation in only 52% of recipients. Thirty percent were status 1 at transplant and PELD scores granted by exception were used for allocation in 18% of patients. There was regional variation in PELD score at allocation and use of exception scores with a significant relationship between PELD score and percentage of exception cases. Regional variation suggests that PELD has not resulted in standardization of listing practices in pediatric liver transplantation.

To define the spectrum of intracranial events and cerebrovascular lesions in patients with Alagille syndrome using magnetic resonance imaging with angiography of the head and medical histories and to correlate the presence of lesions with the clinical outcome of bleeding or ischemic intracranial events.26 patients with Alagille syndrome underwent magnetic resonance imaging with angiography of the head; 22 had no symptoms and underwent study for screening purposes and 4 were symptomatic with neurologic changes. The results of studies and the history of ischemic intracranial events were reviewed.Cerebrovascular abnormalities were detected in 10 of 26 (38%) patients (9 by head magnetic resonance imaging with angiography and 1 by necropsy). The findings included stenoses of the internal carotid arteries unilaterally (n = 5) or bilaterally (n = 3), basilar artery aneurysm (n = 1) and middle cerebral artery aneurysm (n = 1). Among the 9 patients with cerebrovascular abnormalities detected by magnetic resonance imaging with angiography, 5 had no symptoms (23%, 5 of 22) and 4 were symptomatic. Thus, 100% of symptomatic patients had detected abnormalities and 23% of screened, asymptomatic patients had detected anomalies. Screening magnetic resonance imaging with angiography failed to detect vascular anomalies in 2 asymptomatic patients who had fatal ischemic intracranial events years later. There was evidence of progression of vascular abnormalities in 4 patients. Ischemic intracranial events occurred in 10 of 26 (38%) patients and were associated with cerebrovascular abnormalities in 6 of 10 patients.The cerebral vasculopathy of Alagille syndrome predominantly involves the internal carotid arteries. It is more prevalent than would be suggested by the number of symptomatic individuals, appears to be progressive and shares many similarities with moyamoya. Magnetic resonance imaging with angiography is useful to detect these lesions and may have a valuable role in screening for treatable lesions such as aneurysms.

Background— Alagille syndrome (AGS) is a dominantly inherited multisystem disorder involving the liver, heart, eyes, face, and skeleton, caused by mutations in Jagged1 . Intracranial bleeding is a recognized complication and cause of mortality in AGS. There are multiple case reports of intracranial vessel abnormalities and other vascular anomalies in AGS. The objective of this study was to characterize the nature and spectrum of vascular anomalies in AGS. Methods and Results— Retrospective chart review of 268 individuals with AGS was performed. Twenty-five patients (9%) had noncardiac vascular anomalies or events. Sixteen patients had documented structural vascular abnormalities. Two had basilar artery aneurysms, 7 had internal carotid artery anomalies, and another had a middle cerebral artery aneurysm. Moyamoya disease was described in 1 patient. Three of the 16 patients had aortic aneurysms, and 2 had aortic coarctations. One of the patients with a basilar artery aneurysm also had coarctation of the aorta. One of the individuals with an internal carotid artery anomaly also had renal artery stenosis. Nine more patients had intracranial events without documented vessel abnormalities. Vascular accidents accounted for 34% of the mortality in this cohort. Conclusions— The vascular anomalies described in our cohort of AGS individuals identify an underrecognized and potentially devastating complication of this disorder. It is a major cause of morbidity and mortality in this population, accounting for 34% of the mortality. We have also reviewed the body of evidence supporting a role for Jagged1 and the Notch signaling pathway in vascular development.

OBJECTIVE Coagulopathy is an important cause of morbidity and mortality in patients with liver failure. The benefit of traditional therapies to correct coagulation is often limited and short-lived. Our aim is to identify indications for rFVIIa use and the outcome of treatment in children with liver failure. METHODS A retrospective review from July 2000 to December 2001 was performed to identify consecutive patients with acute or chronic liver failure who received rFVIIa. Prothrombin times (PT) before and after therapy were compared by paired t test. RESULTS Fifteen patients were treated with rFVIIa for coagulopathy caused by liver failure. All were receiving fresh frozen plasma (mean infusion rate, 39.7 mL/kg/day) when rFVIIa therapy was started. The mean PT before rFVIIa was 32.0 +/- 7.0 seconds. One hour after infusion, the PT normalized to 13.7 +/- 2.4 seconds (P < 0.0001) and remained significantly reduced at 6 hours (19.8 +/- 5.3 seconds; P < 0.0001). A sustained improvement was maintained during the subsequent 3 days. Five of seven patients with bleeding complications improved clinically after rFVIIa treatment. Two of the bleeding patients also benefited from improved fluid balance as fresh frozen plasma support was reduced. No thrombotic events were attributed to rFVIIa therapy. CONCLUSIONS In patients with liver failure, rFVIIa therapy quickly normalizes the PT and maintains improved hemostasis, even when coagulopathy has been refractory to fresh frozen plasma. Therapy subjectively reduces clinical bleeding and can improve fluid balance, without complications.

UNLABELLED Potential adverse effects of azathioprine (AZA), such as neutropenia and hepatotoxicity, make its use in autoimmune hepatitis (AIH) problematic. OBJECTIVE To determine longitudinal AZA metabolite levels in a cohort of children with AIH, correlate them with therapeutic effects, medication-induced toxicity and adherence. METHODS From January 2000 to January 2002, 122 blood samples from 30 pediatric patients with AIH were prospectively analyzed. Ten patients had previously been treated with AZA (mean dose of 1.3mg/kg/day) for an average of 30 months. At the outset, 24 patients were taking steroids and 10 had cirrhosis/hypersplenism. Routine biochemical studies, 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) levels were assessed every 8 weeks. Red blood cell thiopurine methyltransferase (TPMT) enzyme activity was determined in each patient. AZA dose was adjusted to achieve a target 6-TG level 235-450 pmoles per 8 x 10 RBC. RESULTS 8/10 patients who had previously been treated with standard doses of AZA had 6-TG below target levels. Increasing AZA mean dose by 50% in those patients resulted in 6/10 patients in target range; ALT levels and steroid requirements were reduced. AZA dosing was safely increased in patients with cirrhosis/hypersplenism. In spite of normal TPMT levels, 64% of patients did not make measurable concentrations of 6-MMP. Inappropriately low 6-TG levels revealed non-adherence in 5 patients. Two patients were identified with AZA hepatotoxicity. CONCLUSION AZA metabolite testing in children with AIH is useful in identifying medication toxicity and non-adherence. AZA dose escalation is safe and may be required in order to achieve 6-TG target levels described for inflammatory bowel disease.

Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. This study was performed to determine whether partial external biliary diversion (PEBD) is effective for relief of pruritus and xanthomas in AGS patients who fail conventional medical therapy. Between the years 1985 and 2001, 9 AGS patients underwent PEBD. Complete follow-up data were available for all patients. The average age at PEBD was 4.8 (range 1.4-10) years. The average duration of follow-up was 7.5 (range 0.5-16.0) years. All 9 patients had severe, mutilating pruritus (grade 4) prior to diversion. At 1 year post-PEBD, the average pruritus score was 1.1; 8 patients had only mild scratching when undistracted. Three patients with extensive xanthomas prior to PEBD had complete resolution within 1 year. Mean serum bile salt levels (n = 5) decreased from 136.5 to 37.1 micromol/L and mean cholesterol (n = 7) from 724 to 367 mg/dL 1 year after PEBD. A single 21-year-old patient with PEBD for 14 years experienced an increase in pruritus from grade 1 to grade 4 within 2 months of elective reversal of PEBD. In conclusion, PEBD is effective for treating severe pruritus and hypercholesterolemia in AGS patients without cirrhosis who did not respond to medical therapy. PEBD should be considered as a therapeutic option for these patients before referral for liver transplantation because of morbid complications.

The molecular pathophysiology of cholestasis was poorly understood until recently. The past 20 years have produced great advances in the understanding of the physiology of bile formation, which have led to a better understanding of the defective mechanisms that lead to cholestasis. The recent discovery and characterization of the gene defects involved in several familial cholestatic diseases have led to improved understanding of the molecular mechanisms of cholestasis and, therefore, of bile formation. Still, little is known about the defects in bile formation that lead to neonatal cholestasis. Armed with a new and evolving understanding of the mechanisms of cholestasis, there is a great opportunity to study and understand the pathogenesis of this common condition. Cholestasis is a principal manifestation of hepatobiliary disease in most age groups. The neonate develops cholestasis in response to a wide variety of insults, hepatic and systemic, indicating a relative sensitivity of the mechanisms of bile formation compared with children and adults. Studies of the ontology of bile formation have shown considerable differences between the mature and immature liver with regard to bile formation. While these differences may explain the neonate’s predisposition to cholestasis partially, a full explanation has yet to be developed. This discussion first describes the features of cholestasis, describes the process of bile formation in the mature liver as it is now understood, and examines the process of bile formation and several other metabolic processes in the immature liver. With that background, this article then

We have studied 92 patients with Alagille syndrome (AGS) to determine the frequency of clinical manifestations and to correlate the clinical findings with outcome. Liver biopsy specimens showed paucity of the interlobular ducts in 85% of patients. Cholestasis was seen in 96%, cardiac murmur in 97%, butterfly vertebrae in 51%, posterior embryotoxon in 78%, and characteristic facies in 96% of patients. Renal disease was present in 40% and intracranial bleeding or stroke occurred in 14% of patients. The presence of intracardiac congenital heart disease was the only clinical feature statistically associated with increased mortality (P

Objectives: To describe the patterns of growth, nutritional status, body composition, and resting energy expenditure (REE) in prepubertal children with Alagille syndrome (AGS) before the onset of end-stage liver disease. Study design: Thirteen prepubertal subjects with AGS (8 male; mean age, 6.8 ± 2.8 years) were evaluated for growth parameters, body composition by skinfolds and by dual-energy x-ray absorptiometry, and REE by indirect calorimetry. The children with AGS were compared with a healthy, age-matched reference group of 37 prepubertal children. Results: Compared with healthy children, children with AGS had significantly reduced (P

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic cholestasis 1 [FIC1]) or ABCB11 (encoding bile salt export pump [BSEP]). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. Methods: A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 "FIC1 patients") or ABCB11 (84 "BSEP patients") were evaluated. Results: At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. Conclusions: Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background Partial External Biliary Diversion (PEBD) is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome (AGS). PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome. Methods Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD. Results Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA), bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1) genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP) genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients. Conclusion Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.

Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)—or “neonatal hepatitis” suggesting PFIC—that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or “neonatal hepatitis” suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11. (HEPATOLOGY 2006;44:478–486.)

Objective. X-linked hyper-immunoglobulin M (X-HIM) syndrome is a rare genetic immunodeficiency syndrome caused by mutations in the gene encoding CD40 ligand (CD40L, CD154). Allogeneic hematopoietic stem cell transplantation (HSCT) offers the prospect of immune reconstitution in X-HIM syndrome. Standard HSCT using high-dose chemoradiotherapy can be followed by serious hepatic problems, including veno-occlusive disease, graft-versus-host disease, and/or drug-induced hepatotoxicity. In patients whose liver function is compromised before HSCT, such as in X-HIM syndrome caused by cholangiopathy and hepatitis related to opportunistic infections, there is a higher likelihood of hepatotoxicity. We explored nonmyeloablative HSCT in 2 patients with X-HIM syndrome. Nonmyeloablative HSCT without liver transplant for X-HIM syndrome, to our knowledge, has not been described previously.Methods. Two children with X-HIM syndrome and persistent infections had documented cholangiopathy on liver biopsy. Both children underwent nonmyeloablative HSCT from HLA-matched siblings with fludarabine, busulfan, and anti-thymocyte globulin as their preparative regimen. Graft-versus-host disease prophylaxis consisted of cyclosporine.Results. Both children are >2 years after their HSCT. One remains a mixed chimera, and the other shows 100% donor chimerism. Both children are now free of infections and are no longer dependent on intravenous gammaglobulin. Both show response to immunizations. Both have had resolution of their cholangiopathy.Conclusions. Nonmyeloablative HSCT from HLA-matched siblings can offer immune reconstitution without hepatotoxicity in patients with X-HIM syndrome and preexisting cholangiopathy. Even with stable mixed chimerism after allogeneic HSCT, patients may be able to enjoy a normal phenotype. Nonmyeloablative HSCT warrants additional study in X-HIM syndrome.

Objectives To evaluate the outcomes of octreotide use in children with gastrointestinal bleeding with or without portal hypertension. Methods The medical charts of children who received continuous octreotide infusion for the indication of gastrointestinal bleeding from January 1995 to December 2000 were retrospectively reviewed. Results Twenty-one children with portal hypertension received octreotide infusions (1–2 μg/kg/h) during 35 gastrointestinal bleeding episodes. The duration of infusion ranged from 19 hours to 7 days. Bleeding ceased in 71% of children. Post-treatment rebleeding occurred in 52%, and the mortality was 19%. Response to octreotide, rebleeding, and mortality did not differ significantly between patients with or without intrinsic liver disease. Results Twelve children with gastrointestinal bleeding unrelated to portal hypertension received octreotide during 14 episodes. The duration of octreotide ranged from 3 hours to 36 days. Fifty percent of children had resolution of bleeding during the infusion. Post-treatment rebleeding occurred in 29%, and the mortality was 50%. No major adverse events were observed in either group. Conclusions A high rate of bleeding control was achieved with octreotide during acute gastrointestinal bleeding in children with portal hypertension. However, controlled studies are needed for more definitive description of its clinical effects. The role of octreotide is less clear in gastrointestinal bleeding unrelated to portal hypertension.

Background— Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of JAG1 are found in most individuals with AGS. This study was undertaken to determine the spectrum of cardiovascular phenotypes associated with a JAG1 mutation and/or AGS, investigate potential genotype-phenotype correlations, and begin to correlate clinical outcome with genetic pathogenesis. Methods and Results— We reviewed the records of 200 individuals with a JAG1 mutation or AGS. A total of 187 (94%) subjects had evidence of cardiovascular involvement. Cardiovascular anomalies were identified by imaging in 150 subjects (75%), and 37 (19%) had a peripheral pulmonary stenosis murmur with either a normal echocardiogram or no imaging study. Of the 150 subjects with anomalies confirmed by imaging, right-sided anomalies were present in 123 and left-sided anomalies in 22, with both in 12. Seventeen subjects had other anomalies. The most common abnormality was stenosis/hypoplasia of the branch pulmonary arteries (PAs), which was documented by imaging (n=111) or inferred from a peripheral pulmonary stenosis murmur (n=41) in 76% of subjects. Tetralogy of Fallot was present in 23 subjects and was accompanied by pulmonary atresia in 8. Branch PA phenotype differed between individuals with and without a JAG1 mutation. Among subjects with a JAG1 mutation, there was no correlation between the type or location of mutation and the frequency or type of cardiovascular anomaly. Conclusions— More than 90% of individuals with a JAG1 mutation or AGS have cardiovascular anomalies, with branch PA stenosis the most common abnormality. Cardiovascular phenotype does not correlate with the type or location of JAG1 mutation.

Summary: This article intends to test the hypothesis that gamma-glutamyl transferase (GGT) may be used as a reliable marker to distinguish skeletal muscle damage from liver damage in Duchenne muscular dystrophy (DMD) patients. To demonstrate this, the authors compare the levels of creatine kinase (C