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Introduction:  Evidence supports long-term oral antibiotic prophylaxis to prevent cholangitis after Kasai procedure. Data regarding perioperative intravenous prophylaxis are lacking. Ascending pathogens from the intestine are made responsible for recurrent cholangitis. Therefore, we analyzed the flora in the upper jejunum during the Kasai procedure and their potential impact on postoperative cholangitis., Materials and Methods:  In 26 patients, swabs were taken at the bowel prepared for the Roux-en-Y-loop. Our postoperative protocol includes intravenous third-generation cephalosporins for 2 weeks and rectal steroids starting at day 4. Cholangitis was defined as the postoperative reappearance of acholic stools or increase of serum bilirubin in combination with fevers or increase of inflammatory parameters. In this scenario, Tazocin was administered for another 2 weeks., Results:  Swabs remained sterile in nine patients (34.6%). In 17 patients (65.4%), gram-positive and gram-negative pathogens were identified; all belonging to physiological intestinal flora. A total of 96.2% pathogens were covered by the antibiotic prophylaxis. The cholangitis incidence was 55.6% in the sterile cohort, and 23.5% in the gram-positive and gram-negative cohort ( p  = 0.06). In the cholangitis cohort, no significant differences were detected for the age at Kasai and the pre- and postoperative total bilirubin., Conclusion:  We found that our antibiotic regiment covered bacteria in the upper gastrointestinal (GI) tract in the majority of our patients at the time of Kasai. Nonetheless, a significant proportion of patients developed signs of cholangitis. There was no higher rate of cholangitis in patients with resistant bacteria. Thus, our data do not support the hypothesis of extended postoperative intravenous antibiotics to prevent ascending cholangitis., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: The benefit of laparoscopic Kasai portoenterostomy remains controversial. With the progression of the disease, significant numbers of patients require liver transplantation. It has been reported that reduced internal scarring and fewer adhesions could facilitate the subsequent liver transplantation and thus represent a potential advantage of the laparoscopic technique., Subjects and Methods: All patients undergoing liver transplantation in our hospital between 2006 to 2008 after a laparoscopic or conventional Kasai procedure were included in this retrospective analysis. Primary outcome measure was duration of liver explantation. Secondary outcome measures were total duration of transplantation, amount of blood transfusion, and need for reoperation within the first year., Results: In total, 19 patients were included: 11 patients after open Kasai and 8 patients after laparoscopic Kasai. There was no significant difference in patient characteristics. The mean duration of liver explantation was comparable in laparoscopic (125±8 minutes) and conventional (116±6 minutes) (P>.05) patients. Moreover, we did not identify any significant difference in the need for blood transfusions, total liver transplantation duration, and need for reoperation., Conclusions: We did not detect any measurable benefit of laparoscopic compared with conventional portoenterostomy for subsequent liver transplantation. Thus, prevention of adhesion formation and facilitating subsequent liver transplantation are not rationales for laparoscopic Kasai portoenterostomy.

Objective: A prospective study to compare survival with own liver in laparoscopic versus conventional Kasai portoenterostomy in patients with biliary atresia., Background: Available studies on laparoscopic versus conventional Kasai portoenterostomy focus on short-term results, include small numbers of patients and have design limitations., Methods: A consecutive series of patients underwent laparoscopic Kasai procedure from 2006 to 2007. Conventionally operated control patients consisted of a consecutive series of infants with biliary atresia operated from August 2003 to 2006. All data were ascertained prospectively using the European Biliary Atresia Registry/EBAR registration forms. Primary outcome measure was survival with own liver 6 months after Kasai without being listed for liver transplantation. An interim analysis was planned after data became available for the first 12 patients, who underwent the laparoscopic Kasai procedure. In case of a significantly different interim outcome, the follow-up period should be extended to 24 months until a final decision can be made., Results: Twelve infants underwent laparoscopic Kasai procedure without conversion or revision and there was no revision in the control group of 28 conventionally operated patients. Six months after operation, 5 of 12 laparoscopically operated patients (42%) survived with own liver, compared with 23 of 28 (82%) controls (P < 0.01). The study was stopped due to the significantly higher rate of liver transplantation after laparoscopic operation. Ten patients (83%) after laparoscopic Kasai versus 18 (64%) conventionally operated patients were transplanted after 24 months (P < 0.05) and survival rates with own liver and serum bilirubin <20 μmol/L were 1 (8%) versus 8 (29%), respectively (P < 0.05)., Conclusions: This prospective study shows that the laparoscopic Kasai procedure for biliary atresia is technically feasible. However, the study was stopped after inclusion of 12 laparoscopically operated infants due to a lower survival with the native liver after laparoscopic versus conventional Kasai operation. Superior results after conventional operation were confirmed at follow-up after 24 months. Study registration ID: EBAR 9260/NCT01063699.

Background/aims: Timely diagnosis of biliary atresia (BA) requires key investigations that are less invasive but as accurate as possible. Non-invasive imaging preselects patients before explorative laparotomy is performed. The purpose of this prospective study was to evaluate the accuracy of endoscopic retrograde cholangiopancreaticography (ERCP) in these patients and to discuss its relevance to future diagnostic guidelines in neonatal jaundice., Methods: Over a 7-year period, ERCP was routinely performed in cholestatic patients less than 6 months of age suspected for an extrahepatic origin of cholestasis, most likely BA. Endoscopic diagnosis was correlated with intraoperative findings., Results: In 140 consecutive patients (mean age: 60 days; weight: 4 kg), ERCP excluded BA in 34 (25%) but failed in 18 newborns (13%) for technical reasons. The average procedure time was 23 min, and no severe complications occurred. Explorative laparotomy was performed in 106 patients and revealed BA in 80 cases. In this series, the sensitivity of ERCP for diagnosing biliary atresia was 92% and specificity was 73%., Conclusions: In preselected patients, ERCP is not an alternative to non-invasive imaging, but it avoids unnecessary surgical procedures in almost 25% of the cases. Hence, ERCP is recommended prior to explorative laparotomy in all patients suspected for BA.

Objective: Postoperative adjuvant steroid treatment is reported to improve jaundice-free survival in biliary atresia (BA) patients and to reduce the need for early liver transplantation. However, evidence of all retrospective studies is very limited, although high-dose corticosteroids were favored. The aim of this dosage finding study was to test the most promising corticosteroid protocol in a smaller but representative series, in order to optimize the settings of upcoming prospective and long-term multicenter studies., Methods: Our prospective single-center and open-labeled pilot study on high-dose steroids included 49 consecutive BA patients. Basic data of the study group were not different from 29 controls. In the study group, 20 consecutive patients were treated after the Kasai with methylprednisolone (10 mg/kg day 1 to 5 and 1 mg/kg day 6 to 28)., Results: Overall survival with native liver was 63% after 6 months and 31% after 2 yr, with no statistical difference between the study and control groups. After 2 yr, 27% of all patients were still jaundice-free. With regard to predictive parameters, we found, 6 months after the Kasai, bilirubin < 20 micromol/L as highly sensitive (97%) and specific (93%) for jaundice-free survival with native liver., Conclusions: In contrast to previous reports, this pilot study shows that high-dose steroid pulses after Kasai procedure are not effective in postoperative adjuvant therapy protocols and should be avoided in upcoming multicenter steroid studies. Therefore, we recommend extended and randomized multicenter studies to pre-evaluate the supposed effectiveness of alternative steroid protocols, by comparing, 6 months after the Kasai procedure, the number of patients with normal bilirubin.

The etiology of biliary atresia (BA) is not yet understood, but recent studies have shown inflammation with an up-regulated interferon (IFN) activity in the intra- and extrahepatic bile ducts of patients with BA. These findings support an inflammatory/infectious cause of BA as mimicked in our infective murine model. To study the role of the IFN receptors in our model, we used mice with inactivated INF-alpha/beta receptor A129, with inactivated IFN-gamma receptor G129, or inactivation of both interferon receptors AG129 as well as the wild type controls W129. Mice were infected with rotavirus within 48h of birth and 7 d postpartum. The incidence of BA in each group was determined during a 3 wk period. In the second week the virus load was measured. BA incidence was 76% in A129 and 67% in AG129 animals, whereas in the G129 group only 33% of the pups developed BA. The wild type presented with a BA-incidence of 15%, while 7 d old mice failed to develop BA. There was no significant difference in the virus load of the livers between the groups independent of clinical symptoms. In conclusion, inactivation of type I INF-receptor significantly increases the incidence of BA following postpartal rotavirus infection. This effect is independent of the presence of type II-INF-receptors. Thus, in our model a type I IFN-linked deregulation of the innate immune system appears to be crucial for the induction of biliary atresia.

One hypothesis of the pathogenesis of biliary atresia (BA) is a virus-induced and immune-mediated injury to bile duct cells as mimicked in the rotavirus-induced murine model. This theory is supported by studies showing a predominant T helper cell response type 1-like phenotype of inflammation with increased interferon gamma-induced chemokines in the liver of humans and mice suffering from BA. Recent gene expression profiling studies using microarray analysis showed the induction of a proinflammatory state in human liver specimens with high analogies in extrahepatic biliary tissue of BA mice. The aim of the present study was a microarray analysis of gene expression in the liver of Balb/c mice, comparing infected mice that show the phenotype of BA versus infected mice without symptoms, thus trying to elucidate genes that are not related to the viral origin of this model, but to the specific pathogenesis of the clinical picture of BA. Fifteen mug of RNA, each of three BA-positive and three BA-negative mice, were pooled and comparatively hybridized to spotted cDNA microarrays containing 250 key genes with high relevance to immunological settings. We identified the 40 genes most differentially expressed in mice with and without BA. The majority of genes with higher expression in BA-positive mice encoded proinflammatory cytokines involved in the Th1 pathway, such as CCL2, CCL5, CCR5, CXCL10, CCL2, IL1F5 and in apoptosis, such as DDR3 and granzyme A and B. In this initial study of the molecular characterization of our RRV-induced BA mouse model system, we also found potential novel candidates important to BA etiology, such as growth hormone receptor and insulin-like growth factor. Of particular interest, very low expression of TIMD2 was observed in BA-positive mice. TIMD2 plays a critical role in the regulation of a Th2-type response through the inhibition of IFN gamma.

Based on the hypothesis that autoimmunological factors coregulate the pathomechanism in biliary atresia (BA), adjuvant therapy with steroids has become routine, although its efficacy has never been proven. In 2010, a study on the advantages of budesonide compared to prednisolone in autoimmune hepatitis gave rise to experimental therapy using budesonide as an adjuvant BA treatment. Ninety-five BA patients prospectively received a budesonide 2 mg/dose rectal foam daily for three months (SG). A case-matched control group (CG: 81) was retrospectively recruited. The outcome measures were survival with native liver (SNL), determined at six months and two years after the Kasai procedure. The follow-up rate was 100%. At six months, SNL was statistically not different but became so after two years (SG: 54%; CG: 32%; p < 0.001). No steroid-related side effects were observed, except for eight patients with finally caught-up growth retardation. This study demonstrates for the first time a significantly longer survival with native liver in patients with BA after adjuvant therapy. However, indication, dosage, and duration of any budesonide application is not given in neonates with BA. Hence, we suggest extending the postoperative use of budesonide in a multicenter observational study with a clearly defined follow-up protocol, particularly in terms of potentially underestimated side effects. [ABSTRACT FROM AUTHOR]