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El-Koofy N, Mahmoud E, El Mougy F, Nasr E, Okasha S, El-Karaksy H, Anwar G, El-Shabrawi MH, Badawi NE, Arafa N. Effect of medium chain triglycerides enriched formula on growth of biliary atresia patients after Kasai portoenterostomy. Arab J Gastroenterol 2024; 25:188-193. [PMID: 38378358 DOI: 10.1016/j.ajg.2024.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 01/22/2024] [Accepted: 01/27/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND AND STUDY AIMS Biliary atresia (BA) is the most common cause of neonatal cholestasis, negatively affecting nutritional status, growth, and development. It is the most frequent paediatric indication for liver transplantation. The Kasai portoenterostomy (KPE) operation is an effective procedure with favourable outcomes when performed before two months of age. The present study aimed to assess the nutritional status of patients with biliary atresia who underwent the Kasai operation and to evaluate the effectiveness of nutritional counselling using medium-chain triglyceride (MCT) formulas and proper supplementation on their nutritional status, growth, and vitamin D levels. PATIENTS AND METHODS This prospective observational study included 36 infants with biliary atresia who underwent Kasai portoenterostomy. All patients underwent clinical assessment, anthropometric evaluation, nutritional counselling, and an evaluation of vitamin D levels. Only compliant patients (22/36) were followed up after 3 and 6 months of nutritional counselling. RESULTS Z-scores for weight, triceps skinfold thickness, and mid-upper arm circumference improved significantly after three months, and the height velocity Z-score improved after six months of nutritional counselling using an MCT-containing formula and supplementations. Patients who showed an improvement in cholestasis had better responses. The initial assessment revealed low serum levels of 25-hydroxyvitamin D in 77.8 %, which increased significantly (p = 0.012). CONCLUSION Dietary intervention and supplementation with MCT and micronutrients can improve the nutritional status of children with BA following KPE.
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Affiliation(s)
- Nehal El-Koofy
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | - Eman Mahmoud
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | - Fatma El Mougy
- Department of Clinical and Chemical Pathology, Kasr Al-Ainy Medical School, Cairo University, Egypt.
| | - Engy Nasr
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt.
| | - Sawsan Okasha
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | - Hanaa El-Karaksy
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | - Ghada Anwar
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | | | - Nora E Badawi
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt
| | - Noha Arafa
- Department of Pediatrics, Kasr Al-Ainy Medical School, Cairo University, Egypt.
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Lu X, Jiang J, Shen Z, Chen G, Np YW, Xiao X, Yan W, Zheng S. Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial. Ann Surg 2023; 277:e1200-e1207. [PMID: 35170539 DOI: 10.1097/sla.0000000000005407] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To evaluate the efficacy and side effects of additional postoperative steroid therapy for type 3 BA versus the current routine care. SUMMARY BACKGROUND DATA Whether steroid therapy post-Kasai portoen-terostomy improves the outcomes of BA remains controversial. Clinical evidence from 2 randomized trials in the UK and USA do not support the routine use of steroid in the treatment of BA. METHODS In this open-label randomized controlled trial, patients with type 3 BA were randomized to routine postoperative treatment with or without 10 to 12 weeks of adjuvant steroid treatment. The primary outcome was the postoperative jaundice clearance rate with native liver at 6 months. The secondary outcomes included postoperative jaundice clearance rate at 3, 12, and 24 months, survival with native liver at 12 and 24 months, and SAEs within 3 months. RESULTS Overall, 200 participants were randomized and allocated into either steroid or control group (n = 100/group). The proportion of participants that are jaundice free without liver transplantation was significantly higher in the steroid group than in the control group at 6 months (54.1% vs 31.0%, P = 0.0015). The native liver survival rate was higher postoperatively in the steroid group than in the control group at 12 (66.3% vs 50.0%, P = 0.02) and 24 (57.1% vs 40.0%, P = 0.02) months. The survival time with native liver was significantly longer in the steroid group than in the control group (median survival, steroid vs control: not reached vs 1.21 years, P = 0.02). There were no significant differences between the 2 groups in the mean occurrence of SAEs within 3 months (steroid vs control: 0.63 vs 0.45, P = 0.20). CONCLUSIONS Postoperative adjuvant steroid intervention improved bile drainage and survival with native liver in type 3 BA patients, without increasing early-stage SAEs.
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Affiliation(s)
- Xuexin Lu
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Jingying Jiang
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Zhen Shen
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Gong Chen
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Wu Np
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Xianmin Xiao
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
| | - Weili Yan
- Clinical Trial Unit (CTU), Children's Hospital of Fudan University, Shanghai, China
| | - Shan Zheng
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
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Fligor SC, Hirsch TI, Tsikis ST, Adeola A, Puder M. Current and emerging adjuvant therapies in biliary atresia. Front Pediatr 2022; 10:1007813. [PMID: 36313875 PMCID: PMC9614654 DOI: 10.3389/fped.2022.1007813] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 09/26/2022] [Indexed: 11/21/2022] Open
Abstract
Following Kasai hepatic portoenterostomy (HPE), most patients with biliary atresia will eventually require liver transplantation due to progressive cirrhosis and liver failure. Preventing liver transplantation, or even delaying eventual liver transplantation, is the key to improving long-term outcomes. This review first examines the commonly used adjuvant therapies in post-HPE biliary atresia and the strength of the evidence supporting these therapies. Next, it examines the evolving frontiers of management through a comprehensive evaluation of both recently completed and ongoing clinical trials in biliary atresia. Promising therapies used in other cholestatic liver diseases with potential benefit in biliary atresia are discussed. Improving post-HPE management is critical to prevent complications, delay liver transplantation, and ultimately improve the long-term survival of patients with biliary atresia.
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Affiliation(s)
- Scott C Fligor
- Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Thomas I Hirsch
- Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Savas T Tsikis
- Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Andrew Adeola
- Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
| | - Mark Puder
- Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
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Kuebler JF, Madadi-Sanjani O, Pfister ED, Baumann U, Fortmann D, Leonhardt J, Ure BM, Manns MP, Taubert R, Petersen C. Adjuvant Therapy with Budesonide Post-Kasai Reduces the Need for Liver Transplantation in Biliary Atresia. J Clin Med 2021; 10:jcm10245758. [PMID: 34945055 PMCID: PMC8704494 DOI: 10.3390/jcm10245758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 11/26/2021] [Accepted: 12/03/2021] [Indexed: 12/12/2022] Open
Abstract
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.
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Affiliation(s)
- Joachim F. Kuebler
- Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany; (J.F.K.); (O.M.-S.); (D.F.); (B.M.U.)
| | - Omid Madadi-Sanjani
- Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany; (J.F.K.); (O.M.-S.); (D.F.); (B.M.U.)
| | - Eva D. Pfister
- Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, 30625 Hannover, Germany; (E.D.P.); (U.B.)
| | - Ulrich Baumann
- Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, 30625 Hannover, Germany; (E.D.P.); (U.B.)
| | - David Fortmann
- Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany; (J.F.K.); (O.M.-S.); (D.F.); (B.M.U.)
| | - Johannes Leonhardt
- Clinic for Pediatric Surgery, Klinikum Braunschweig, 38118 Braunschweig, Germany;
| | - Benno M. Ure
- Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany; (J.F.K.); (O.M.-S.); (D.F.); (B.M.U.)
| | - Michael P. Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany; (M.P.M.); (R.T.)
| | - Richard Taubert
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany; (M.P.M.); (R.T.)
| | - Claus Petersen
- Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany; (J.F.K.); (O.M.-S.); (D.F.); (B.M.U.)
- Correspondence: ; Tel.: +49-511-532-9047; Fax: +49-511-532-9059
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Kakos CD, Ziogas IA, Alexopoulos SP, Tsoulfas G. Management of biliary atresia: To transplant or not to transplant. World J Transplant 2021; 11:400-409. [PMID: 34631471 PMCID: PMC8465510 DOI: 10.5500/wjt.v11.i9.400] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 06/26/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Kasai procedure (KP) and liver transplantation (LT) represent the only therapeutic options for patients with biliary atresia (BA), the most common indication for LT in the pediatric population. However, KP represents by no means a radical option but rather a bridging one, as nearly all patients will finally require a liver graft. More and more experts in the field of transplant surgery propose that maybe it is time for a paradigm change in BA treatment and abandon KP as transplantation seems inevitable. Inadequacy of organs yet makes this option currently not feasible, so it seems useful to find ways to maximize the efficacy of KP. In previous decades, multiple studies tried to identify these factors which opt for better results, but in general, outcomes of KP have not improved to the level that was anticipated. This review provides the framework of conditions which favor native liver survival after KP and the ones which optimize a positive LT outcome. Strategies of transition of care at the right time are also presented, as transplantation plays a key role in the surgical treatment of BA. Future studies and further organization in the transplant field will allow for greater organ availability and better outcomes to be achieved for BA patients.
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Affiliation(s)
| | - Ioannis A Ziogas
- Surgery Working Group, Society of Junior Doctors, Athens 15123, Greece
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37212, United States
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN 37212, United States
| | - Georgios Tsoulfas
- Department of Transplant Surgery, Aristotle University School of Medicine, Thessaloniki 54622, Greece
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Abstract
The treatment of biliary atresia (BA) is predominantly surgical with firstly an attempt at restoration of bile flow from the native liver by wide excision of the obstructed, obliterated extrahepatic biliary tree to the level of the porta hepatis and a portoenterostomy using a long Roux loop-Kasai portoenterostomy (KPE). Liver transplantation is reserved for those that fail this and for those where surgery is considered futile for reasons of age or stage of disease. As the aetiology of BA remains ill-defined, so adjuvant treatment has been largely based on pragmatism, trial and error. Systematic analysis of the few randomized placebo-controlled trial data and less well-controlled cohort studies have suggested benefit from post-operative high-dose steroids and ursodeoxycholic acid (UDCA) while the benefit of long-term prophylactic antibiotics, bile acid sequestrants (e.g., colestyramine) or probiotics remains unproven. Newer modalities such as antiviral therapy (AVT), immunoglobulin, FXR agonists (e.g., obeticholic acid), ileal bile acid transporter (IBAT) antagonists (e.g., maralixibat) remain unproven. This article reviews the current evidence for the efficacy of adjuvant medical therapy in BA.
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Affiliation(s)
- Jessica Burns
- Department of Paediatric Surgery, King's College Hospital, London, UK
| | - Mark Davenport
- Department of Paediatric Surgery, King's College Hospital, London, UK
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Tanaka Y, Shirota C, Tainaka T, Sumida W, Oshima K, Makita S, Tanaka T, Tani Y, Chiba K, Uchida H. Efficacy of and prognosis after steroid pulse therapy in patients with poor reduction of jaundice after laparoscopic Kasai portoenterostomy. Pediatr Surg Int 2019; 35:1059-1063. [PMID: 31396738 DOI: 10.1007/s00383-019-04537-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/01/2019] [Indexed: 11/25/2022]
Abstract
PURPOSE High-dose postoperative steroid therapy after Kasai portoenterostomy is reported to improve jaundice clearance and a strong anti-inflammatory activity might prevent fibrous tissue formation which is often observed at the porta hepatis in revision surgery. We started steroid pulse therapy for the patients with cessation of decrease in jaundice and aimed to evaluate the efficacy in this study. METHODS The demographics and outcomes of patients who underwent laparoscopic Kasai portoenterostomy and received steroid pulse therapy within 2 months postoperatively between September 2014 and December 2018 were retrospectively reviewed; the therapy was determined successful when the serum total bilirubin level decreased to or below two-thirds of the pre-therapy level after 2 weeks. Patient data in the successful group were compared with those in the unsuccessful group. RESULTS Steroid pulse therapy was successful in seven of 16 patients (43.8%). The percentage of patients whose serum total bilirubin level decreased to normal was significantly higher in the successful group at 3 months (85.7% vs. 11.1%, P = 0.0028) and after all (100% vs. 33.3%, P = 0.011). CONCLUSIONS Steroid pulse therapy was effective for some patients. Unsuccessful cases may have little chances of jaundice clearance; revision Kasai portoenterostomy would be a good option.
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Affiliation(s)
- Yujiro Tanaka
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Chiyoe Shirota
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takahisa Tainaka
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Wataru Sumida
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Kazuo Oshima
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Satoshi Makita
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Tomoko Tanaka
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yukiko Tani
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Kosuke Chiba
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hiroo Uchida
- Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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8
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Parolini F, Davenport M. Biliary Atresia: New Developments. NEONATAL SURGERY 2019:387-399. [DOI: 10.1007/978-3-319-93534-8_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Tyraskis A, Parsons C, Davenport M, Cochrane Hepato‐Biliary Group. Glucocorticosteroids for infants with biliary atresia following Kasai portoenterostomy. Cochrane Database Syst Rev 2018; 5:CD008735. [PMID: 29761473 PMCID: PMC6494535 DOI: 10.1002/14651858.cd008735.pub3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Biliary atresia is a life-threatening disease characterised by progressive destruction of both intra- and extra-hepatic biliary ducts. The mainstay of treatment is Kasai portoenterostomy, as soon as the disease has been confirmed. Glucocorticosteroids are steroid hormones which act on the glucocorticoid receptor and have a range of metabolic and immunomodulatory effects. Glucocorticosteroids are used to improve the postoperative outcomes in infants who have undergone Kasai portoenterostomy. OBJECTIVES To assess the beneficial and harmful effects of glucocorticosteroid administration versus placebo or no intervention following Kasai portoenterostomy in infants with biliary atresia. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), and online trial registries (last search: 20 December 2017) for randomised controlled trials. SELECTION CRITERIA We included randomised clinical trials which assessed glucocorticosteroids for infants who have undergone Kasai portoenterostomy. For harm, we also considered quasi-randomised studies, observational studies, and case-control studies that were identified amongst the search results. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We assessed the risk of bias for each trial according to prespecified domains. We analysed data using both random-effects and fixed-effect models. We performed the analyses using Review Manager 5.3 and Trial Sequental Analysis software. We considered a P value of 0.025 or less, two-tailed, as statistically significant. We planned to calculate risk ratios (RRs) for dichotomous outcomes, and the mean difference (MD) for continuous outcomes. For all association measures, we planned to use 95% confidence intervals (CIs) as well as Trial Sequential Analysis-adjusted CIs. We used Trial Sequential Analyisis to control the risks of random errors; however, we were often unable to implement this beyond calculating the required information size as there were few trials and data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS We found two randomised controlled trials fulfilling the inclusion criteria of our review. The trials provided data for meta-analysis. We judged the two trials as trials at low risk of bias. The two trials randomised a total of 213 infants to glucocorticosteroids versus placebo. In our Trial Sequential Analysis, the required information size (that is, the meta-analytic sample size) was not reached for any outcome. Trials were funded by charities, public organisations, and received support from private sector companies, none of which seemed to have an interest in the outcome of the respective trials. The effect of glucocorticosteroids after Kasai portoenterostomy on all-cause mortality is uncertain; the confidence interval is consistent with appreciable benefit and harm (RR 1.00; 95% CI 0.14 to 6.90; low-certainty evidence). The results showed little or no difference in adverse effects between the use of glucocorticosteroids or placebo after Kasai portoenterostomy, however this analysis was based on a single trial and we have low certainty in the result (RR 1.02; 95% CI 0.87 to 1.20;). Available data suggest that the proportions of infants who do not clear their jaundice at six months is similar between the two groups (RR 0.89; 95% CI 0.67 to 1.17; low-certainty evidence). All-cause mortality or liver transplantation did not differ at two years between the two groups (RR 1.00; 95% CI 0.72 to 1.39; low-certainty evidence). There were no data regarding health-related quality of life.Our searches also yielded 19 observational studies, some of them containing limited information on harmful effects of glucocorticosteroid treatment. We presented the extracted information narratively. We identified one further ongoing trial with no currently available results. AUTHORS' CONCLUSIONS The two meta-analysed randomised clinical trials present insufficient evidence to determine the effects of using glucocorticosteroids versus placebo after Kasai portoenterostomy in infants with biliary atresia on any of the primary or secondary review outcomes. There is insufficient evidence to support glucocorticosteroid use in the postoperative management of infants with biliary atresia for long-term outcomes of all-cause mortality or liver transplantation. It is also unclear if glucocorticosteroids are able to reduce the numbers of infants who did not clear their jaundice by six months. Further randomised, placebo-controlled trials are required to be able to determine if glucocorticosteroids may be of benefit in the postoperative management of infants with biliary atresia treated with Kasai portoenterostomy. Such trials need to be conducted as multicentre trials.
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Affiliation(s)
| | - Christopher Parsons
- Great Ormond Street HospitalSpecialist Neonatal and Paediatric SurgeryGreat Ormond StreetLondonUKWC1N 1JH
| | - Mark Davenport
- King's College HospitalDepartment of Paediatric SurgeryLondonUK
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10
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Davenport M. Adjuvant therapy in biliary atresia: hopelessly optimistic or potential for change? Pediatr Surg Int 2017; 33:1263-1273. [PMID: 28940004 DOI: 10.1007/s00383-017-4157-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2017] [Indexed: 12/17/2022]
Abstract
Given that the aetiology of biliary atresia (BA) is complex and that there is a multiplicity of possible pathogenic mechanisms then it is perhaps not surprising that the evidence for effect of a number of different agents is contradictory. Post-operative cholangitis for instance is common, bacterial in origin and various antibiotic regimens have been tested (although none in a randomized trial) but continuation beyond the early post-operative period does not appear to offer any greater protection. There is an inflammatory reaction in about 25-35% of cases of BA illustrated by abnormal expression of class II antigen and upregulation of ICAM, VCAM and E-selectin with an infiltrate of immune-activated T cells (predominantly CD4 + Th1 and Th17) and NK cells and a systemic surge in inflammatory cytokines (e.g. TNF-α, IL-2, IL-12). This has potential as a therapeutic target and is the main hypothesis behind the rationale use of steroids. The first report of steroids was published in 1985 by Karrer and Lilly as "blast" therapy to treat recalcitrant cholangitis, followed by a multiplicity of small-scale uncontrolled studies suggesting benefit. To date there has been one randomized placebo-controlled study with a low-dose (prednisolone 2 mg/kg/day) regimen (2007); one with a high-dose (IV prednisolone 4 mg/kg/day regimen) (2014); two prospective high-dose open-label studies (2013); a prospective comparison of low- and high-dose regimen and a large (380 infants) retrospective comparison. The most recent meta-analysis (2016) identified a significant difference in clearance of jaundice at 6 months (OR 1.59, 95% CI 1.03-2.45, P = 0.04), in patients treated with high-dose steroids, particularly if < 70 days at surgery. Ursodeoxycholic acid (UDCA) may increase choleresis or change the ratio of endogenous bile acids to a less hydrophobic and, therefore, less toxic millieu. UDCA may protect cholangiocyte membranes against damage and perhaps reduce the tendency to fibrogenesis. Biochemical benefit has been shown in a single crossover trial in older BA children who had cleared their jaundice. Other potential adjuvant therapies include immunoglobulin therapy, anti-viral agents and Chinese herbs although real evidence of benefit is lacking.
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Affiliation(s)
- Mark Davenport
- Department of Paediatric Surgery, King's College Hospital, London, SE5 9RS, UK.
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11
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Tyraskis A, Parsons C, Davenport M. Glucocorticosteroids for infants with biliary atresia following Kasai portoenterostomy. Hippokratia 2016. [DOI: 10.1002/14651858.cd008735.pub2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
| | - Christopher Parsons
- Great Ormond Street Hospital; Specialist Neonatal and Paediatric Surgery; Great Ormond Street London UK WC1N 1JH
| | - Mark Davenport
- King's College Hospital; Department of Paediatric Surgery; London UK
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12
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Tyraskis A, Davenport M. Steroids after the Kasai procedure for biliary atresia: the effect of age at Kasai portoenterostomy. Pediatr Surg Int 2016; 32:193-200. [PMID: 26590818 PMCID: PMC4756036 DOI: 10.1007/s00383-015-3836-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/02/2015] [Indexed: 12/25/2022]
Abstract
The use of adjuvant steroids following Kasai porteoenterostomy (KPE) for biliary atresia is controversial. The aim of this study was twofold: a systematic review of published literature and an update of the clinical Kings College Hospital series to look for evidence of an effect of age on the outcome in a group of BA infants treated with high-dose steroids. This clinical study included infants treated between January 2006 and June 2014 who underwent KPE by day 70 of life and who received high-dose steroids (oral prednisolone starting 5 mg/kg/day). They were subdivided into cohorts according to age at which KPE was performed. The outcome measured was clearance of jaundice (<20 µmol/L) by 6 months and native liver survival. R × C χ(2) analysis and log-rank tests were used, respectively, and P ≤ 0.05 was regarded as significant. 104 infants were included with a median age at KPE of 45 (range 12-70) days. 71/104 (67 %) cleared their jaundice by 6 months of age. Age-cohort analysis showed a trend (P = 0.03) favouring early KPE (e.g. 100 % of 11 infants operated on <30 days clearing their jaundice compared to 66 % of those operated on between 61 and 70 days). There was a significant native liver survival benefit for those operated on <45 days (5 year NLS estimate 69 versus 46 %; P = 0.05). Clearance of jaundice is related to the age at KPE in infants who receive high-dose steroids. Native liver survival appears to be improved as a result of this. This is the first study to show tangible longer-term benefit from high-dose steroids in biliary atresia.
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Affiliation(s)
- Athanasios Tyraskis
- Department of Paediatric Surgery, King’s College Hospital, Denmark Hill, London, SE5 9RS UK
| | - Mark Davenport
- Department of Paediatric Surgery, King’s College Hospital, Denmark Hill, London, SE5 9RS UK
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Thakur RK, Davenport M. Improving treatment outcomes in patients with biliary atresia. Expert Opin Orphan Drugs 2014. [DOI: 10.1517/21678707.2014.973402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Bezerra JA, Spino C, Magee JC, Shneider BL, Rosenthal P, Wang KS, Erlichman J, Haber B, Hertel PM, Karpen SJ, Kerkar N, Loomes KM, Molleston JP, Murray KF, Romero R, Schwarz KB, Shepherd R, Suchy FJ, Turmelle YP, Whitington PF, Moore J, Sherker AH, Robuck PR, Sokol RJ. Use of corticosteroids after hepatoportoenterostomy for bile drainage in infants with biliary atresia: the START randomized clinical trial. JAMA 2014; 311:1750-9. [PMID: 24794368 PMCID: PMC4303045 DOI: 10.1001/jama.2014.2623] [Citation(s) in RCA: 131] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
IMPORTANCE Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome. OBJECTIVE To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. DESIGN, SETTING, AND PATIENTS The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. INTERVENTIONS Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy. MAIN OUTCOMES AND MEASURES The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. RESULTS The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008). CONCLUSIONS AND RELEVANCE Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00294684.
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Affiliation(s)
- Jorge A Bezerra
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | | | | | | | | | - Kasper S Wang
- Children's Hospital Los Angeles and University of Southern California, Los Angeles
| | - Jessi Erlichman
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Barbara Haber
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania17Dr Haber is now with Merck Research Laboratories, Upper Gwynedd, Pennsylvania
| | - Paula M Hertel
- Baylor College of Medicine and Texas Children's Hospital, Houston
| | - Saul J Karpen
- Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia
| | - Nanda Kerkar
- Mount Sinai School of Medicine, New York, New York18Dr Kerkar is now with Children's Hospital Los Angeles and University of Southern California, Los Angeles
| | | | - Jean P Molleston
- Indiana University School of Medicine and Riley Hospital for Children, Indianapolis
| | | | - Rene Romero
- Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia
| | | | - Ross Shepherd
- Baylor College of Medicine and Texas Children's Hospital, Houston
| | - Frederick J Suchy
- University of Colorado School of Medicine and Children's Hospital Colorado, Aurora
| | | | | | | | - Averell H Sherker
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
| | - Patricia R Robuck
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
| | - Ronald J Sokol
- University of Colorado School of Medicine and Children's Hospital Colorado, Aurora
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Improved outcome of biliary atresia with postoperative high-dose steroid. Gastroenterol Res Pract 2013; 2013:902431. [PMID: 24348545 PMCID: PMC3857902 DOI: 10.1155/2013/902431] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 10/30/2013] [Accepted: 10/30/2013] [Indexed: 12/14/2022] Open
Abstract
Objective. The dosage, duration, and the benefits of high-dose steroid treatment and outcome in biliary atresia (BA) remain controversial. In this study, we evaluated the impact of high-dose steroid therapy on the outcome of BA after the Kasai procedure. Methods. Intravenous prednisolone administration was started 1 week after surgery, followed by 8 to 12 weeks of oral prednisolone. Total bilirubin (TB) levels (3, 6, and 12 months after surgery), early onset of cholangitis, and two-year native liver survival were evaluated. Results. 53.4%, 56.9%, and 58.1% of the patients in the high-dose steroid group were jaundice-free 3, 6, and 12 months after surgery, respectively; these values were significantly higher than the 38.7%, 39.4%, and 43.3% of the low-dose steroid group. One year after surgery, the incidence of cholangitis in the high-dose group (32.0%) was lower than that in the low-dose group (48.0%). Infants with native liver in the high-dose group had a better two-year survival compared to those in the low-dose steroid group (53.7% versus 42.6%). Conclusions. The high-dose steroid protocol can reduce the incidence of cholangitis, increase the jaundice-free rate, and improve two-year survival with native liver after the Kasai operation.
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Davenport M, Parsons C, Tizzard S, Hadzic N. Steroids in biliary atresia: single surgeon, single centre, prospective study. J Hepatol 2013; 59:1054-8. [PMID: 23811305 DOI: 10.1016/j.jhep.2013.06.012] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 06/13/2013] [Accepted: 06/17/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS The effect of adjuvant steroids in infants with biliary atresia (BA) is not clear and evidence of benefit is lacking. METHODS During the period Jan. 2000-Dec. 2011, 153 infants with isolated (CMV IgM-ve) BA underwent Kasai portoenterostomy (KPE) at<70 days. They were divided into three groups: LOW-dose steroid (from a previous randomized trial; starting prednisolone 2mg/kg/day, n=18), HIGH-dose steroid (starting prednisolone 5mg/kg/day, n=44), and NO steroid [n=72+19 placebo (from randomized trial)=91]. Outcome was assessed by early liver biochemistry, clearance of jaundice (<20 μmol/L), and actuarial native liver survival. Data are quoted as median (IQ range) and compared with non-parametric ANOVA, Chi or Log-rank tests as appropriate. p ≤ 0.05 was regarded as significant. RESULTS All three groups were comparable for age (ANOVA, p=0.31) and a surrogate marker of liver fibrosis [aspartate-aminotransferase index (APRi), ANOVA, p=0.67]. At 1 month post KPE, there was a significant reduction in bilirubin [58 (25-91) vs. 91 (52-145)μmol/L, p=0.0015], AST [118 (91-159) vs. 155 (108-193)IU/L, p=0.0015], and APRi [0.49 (0.28-0.89) vs. 0.82 (0.45-1.2), p=0.005] for HIGH vs. NO steroid. There was a significant increase in % clearance of jaundice with the use of steroids [47/91 (52%) vs. 12/18 (67%) vs. 29/44 (66%); steroids vs. no steroids, p=0.037]. There was no statistical difference in 4-year patient survival (96% vs. 94% vs. 95%) or native liver survival (4 year=46% vs. 50 vs. 57%). CONCLUSIONS The adjuvant use of prednisolone significantly improved early post-operative liver biochemistry (especially at the higher dose), and increased the proportion of infants who cleared their jaundice at 6 months post-KPE.
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Affiliation(s)
- Mark Davenport
- Department of Paediatric Surgery, King's College Hospital, London SE5 9RS, UK.
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Abstract
PURPOSE We aimed to evaluate early response to two different corticosteroids doses after Kasai portoenterostomy for biliary atresia (BA). METHODS A prospective, randomized trial was performed in infants from the nationwide BA registry with type 3 BA. Sixty-nine infants were randomized to receive either 4 mg/kg/day (group A, n = 35) or 2 mg/kg/day prednisolone (group B, n = 34). The corticosteroids were started on postoperative day 7, and the dose was tapered toward day 30. Results of liver function tests on days 31 and 60 were compared between the groups. RESULTS Mean bilirubin, AST, ALT, and GGT levels did not significantly differ between the groups. However, the levels of total and direct bilirubin of infants <70 days old at surgery significantly differed between the groups. Four patients from group A and five from group B, dropped out of the study. Complications during the first month after PE were comparable between the groups. CONCLUSIONS An initial 4 mg/kg/day dose did not significantly improve liver function, except that bilirubin levels were lower in the subgroup of infants <70 days old at surgery. There were no significant complications with either dose of corticosteroids.
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Andrade WDC, Silva LFFD, Coelho MCDM, Tannuri ACA, Alves VAF, Tannuri U. Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF-β and VEGF. Clinics (Sao Paulo) 2012; 67:1455-61. [PMID: 23295601 PMCID: PMC3521810 DOI: 10.6061/clinics/2012(12)17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 08/15/2012] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVE During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.
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Affiliation(s)
- Wagner de Castro Andrade
- Faculdade de Medicina da Universidade de São Paulo, Pediatric Surgery Division, Laboratory of Pediatric Surgery (LIM-30) and Laboratory of Hepatic Pathology (LIM-14), São Paulo/SP, Brazil.
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Does adjuvant steroid therapy post-Kasai portoenterostomy improve outcome of biliary atresia? Systematic review and meta-analysis. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2011; 25:440-4. [PMID: 21912769 DOI: 10.1155/2011/125610] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear. OBJECTIVE To systematically review the literature and perform a meta-analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy (KP) on BA outcome. METHODS A systematic review and meta-analysis of randomized trials and⁄or observational studies that examined the role of steroids on BA outcomes published between January 1969 and June 2010 was conducted. Studies were identified using the Medline, PubMed, EMBASE and Cochrane databases. RESULTS Sixteen observational studies and one randomized controlled trial (RCT) were found. Four of the 16 observational studies (160 participants) and the RCT (73 participants) met the entry criteria and were eligible to be included in the analysis. There was no statistically significant difference in the effect of steroids either on normalizing serum bilirubin levels at six months (pooled OR 1.48 [95% CI 0.67 to 3.28]) or in delaying the need for early liver transplantation (within the first year post-KP (pooled OR 0.59 [95% CI 0.21 to 1.72]). CONCLUSION The present meta-analysis did not find a significant effect of steroid over standard therapy, either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP. RCT studies of sufficient size and comprehensive design using high-dose steroids are needed to determine the effectiveness of steroids on the short and intermediate post-KP outcomes for BA patients.
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Suzuki T, Hashimoto T, Kondo S, Sato Y, Hussein MH. Evaluating patients' outcome post-Kasai operation: a 19-year experience with modification of the hepatic portoenterostomy and applying a novel steroid therapy regimen. Pediatr Surg Int 2010; 26:825-30. [PMID: 20589382 DOI: 10.1007/s00383-010-2637-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/08/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND We reported a modification of the hepatic portoenterostomy (HPE) for biliary atresia with favorable results. HPE is associated with a risk of hepatic impairment, so we adopted a novel steroid therapy regimen well suited to our procedure. This paper reports the results of our experience. PATIENTS AND METHODS Between 1991 and 2009, 53 patients (18 boys, 35 girls) underwent modified HPE with novel steroid therapy, which consisted of administering hydrocortisone immediately after surgery, followed by intravenous administration of prednisolone. The number of patients who became normal total bilirubin (TB) levels, frequency of early onset cholangitis and other postoperative complications, and outcomes were retrospectively studied. RESULTS The TB levels in 43 of the 53 patients became normal. Cholangitis was observed in seven, but all of them recovered. Other postoperative complications were noted in eight, but with no fatal cases. Of the 11 patients who underwent living-donor liver transplantation, 3 died after the transplant. Of the 53 patients, 39 are alive without liver transplantation and 34 have normal TB (range of observation period: 18 years and 9-2 months). CONCLUSIONS The novel steroid regimen may have contributed to the outcome and appears to be well suited to the modified HPE.
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Affiliation(s)
- Tatsuya Suzuki
- Division of Pediatric Surgery and Transplant Surgery, Nagoya City University Hospital, Mizuho-ku, Nagoya, Aichi, Japan.
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Lao OB, Larison C, Garrison M, Healey PJ, Goldin AB. Steroid use after the Kasai procedure for biliary atresia. Am J Surg 2010; 199:680-4. [PMID: 20466116 PMCID: PMC2871160 DOI: 10.1016/j.amjsurg.2010.01.014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2009] [Revised: 01/19/2010] [Accepted: 01/19/2010] [Indexed: 11/29/2022]
Abstract
BACKGROUND The aim of this study was to describe patients undergoing the Kasai procedure at children's hospitals, evaluate outcomes, and analyze the association of these outcomes with systemic steroid use. METHODS Biliary atresia patients (International Classification of Diseases, Ninth Revision, code 751.61) who underwent Kasai procedures at freestanding children's hospitals in the Pediatric Health Information System database from 2003 to 2008 were identified. Descriptive characteristics were examined, and regression analyses were used to determine whether postoperative steroid use was associated with length of stay, mortality, or cholangitis. RESULTS Of the 516 children identified (40% male, 50% aged < 2 months), 239 (46%) received perioperative steroids. The mean total and postoperative lengths of stay were 14.5 +/- 19.7 and 11.3 +/- 16.3 days, respectively. Postoperative steroid use was significantly associated with a 3.5-day decrease in postoperative length of stay (95% confidence interval, .03-6.97). CONCLUSIONS Perioperative steroids after the Kasai procedure are associated with shorter postoperative length of stay. Work is needed to ascertain whether this relationship is causal.
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Affiliation(s)
- Oliver B Lao
- Department of Surgery, Seattle Children's Hospital, Seattle, WA, USA.
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Andrade WDC, Tannuri U, da Silva LFF, Alves VAF. Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals. J Pediatr Surg 2009; 44:2071-7. [PMID: 19944210 DOI: 10.1016/j.jpedsurg.2009.05.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2009] [Revised: 05/10/2009] [Accepted: 05/11/2009] [Indexed: 01/21/2023]
Abstract
BACKGROUND Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai's portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. METHODS In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. RESULTS The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. CONCLUSIONS Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces.
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Affiliation(s)
- Wagner de Castro Andrade
- Pediatric Surgery Division, Laboratory of Pediatric Surgery, University of Sao Paulo Medical School, CEP 01246-903 Sao Paulo, Brazil
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Mieli-Vergani G, Vergani D. Biliary atresia. Semin Immunopathol 2009; 31:371-81. [PMID: 19533128 DOI: 10.1007/s00281-009-0171-6] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2009] [Accepted: 06/01/2009] [Indexed: 12/17/2022]
Abstract
Biliary atresia (BA) is a condition unique to infancy. It results from inflammatory destruction of the intrahepatic and extrahepatic bile ducts. It is the most frequent surgically correctable liver disorder in infancy and the most frequent indication for liver transplantation in paediatric age. Clinical presentation is in the first few weeks of life with conjugated hyperbilirubinaemia (dark urine and pale stools); other manifestations of liver disease, such as failure to thrive, splenomegaly and ascites, appear only later, when surgery is unlikely to be successful. Hence, all infants with conjugated hyperbilirubinaemia must be urgently referred to specialised centres for appropriate treatment. Success of surgery depends on the age at which it is performed. With corrective surgery, followed, when necessary, by liver transplantation, the overall survival rate is approximately 90%. The cause of BA is unknown, but there is evidence for the involvement of infectious, genetic and immunologic mechanisms, which will be discussed in this review.
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Affiliation(s)
- Giorgina Mieli-Vergani
- Paediatric Liver Centre, Institute of Liver Studies, King's College London School of Medicine, King's College Hospital, Denmark Hill, London, SE5 9RS, UK.
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Selected summary. Extrahepatic biliary atresia (EHBA) is still a significant medical and economic burden to patients and families. J Pediatr Gastroenterol Nutr 2009; 48:115-6. [PMID: 19172135 DOI: 10.1097/mpg.0b013e318180ec7c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Chung HY, Kak Yuen Wong K, Cheun Leung Lan L, Kwong Hang Tam P. Evaluation of a standardized protocol in the use of steroids after Kasai operation. Pediatr Surg Int 2008; 24:1001-4. [PMID: 18679691 DOI: 10.1007/s00383-008-2200-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/08/2008] [Indexed: 02/06/2023]
Abstract
Although the Kasai operation is still the treatment of choice for infants with biliary atresia, the long-term success rate, as defined by survival without transplantation, is only about 25-40%. It has been proposed that post-operative inflammatory changes affect the bile flow and eventually lead to cholangitis and liver failure. Recent case reports have suggested that the administration of steroids post-operatively can improve outcomes. Since 2004, our unit has adopted a strict protocol for the use of post-operative steroids for patients who undergo Kasai operation. The aim of this study is to access the early outcomes of these patients. A retrospective analysis was carried out for all patients who received Kasai operation between 1996 and 2006. For the treatment group, patients all received prednisolone at 4 mg/kg 1 week after operation as guided by protocol. The demographics and outcomes, including post operative bilirubin level, episodes of cholangitic attack, the need for early liver transplantation (transplant within 1 year of Kasai), and transplantation-free survival, were noted. Statistical analysis was done using Fisher's exact test and unpaired t-test when appropriate. A value of P < 0.05 was considered to be statistically significant. Kasai operation was performed in 30 patients (11 boys and 19 girls) during the study period. Thirteen patients received post-operative prednisolone according to protocol. The average age at operation and the mean preoperative bilirubin levels for the steroid and non-steroid group were not significantly different. A normal post-operative bilirubin (defined as bilirubin level less than 20 mumol/L) was achieved at 6 months in 7 (53.9%) patients who received steroid and 8 (47.0%) patients who did not (P = 0.71). A statistically significant reduction in the post-operative bilirubin level was also seen at 3 and 6 months in the steroid group. Early liver transplantation was required in 5 (38.5%) patients with steroid and 5 (29.4%) patients without it (P = 0.60). No significant difference in terms of cholangitic attack was observed. There was also no steroid-associated complication reported. We conclude that lower post-operative bilirubin level can be achieved with the routine use of prednisolone. However, there is no statistical improvement in terms of early liver transplantation and cholangitis. This may be attributed to the small sample size of our study population. Based on this pilot study, a multi-centre randomized trial is needed.
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Affiliation(s)
- Ho Yu Chung
- Department of Surgery, QMH, Hong Kong, China.
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Abstract
PURPOSE OF REVIEW The purpose of this study is to review both the basic science and clinical advancements in the last 12 months that have furthered our understanding of biliary atresia. RECENT FINDINGS Early diagnosis and further understanding of the disease process may be the next major step in advancement. Stool color cards have been shown to be an accurate screening tool. Basic science developments have focused on defects in morphogenesis, immunologic dysregulation, and viral infection as the major theories of causes. There have been initial reports of minimally invasive approaches to hepatic portoenterostomy but there has been little comparative study. Postoperative corticosteroid therapy remains an area of debate without definitive data. Early postoperative testing of serum bilirubin levels and hepatobiliary scintigraphy are showing strong correlation with long-term outcomes. The comparison of regions with decentralization policies compared with those with central referral policies is providing a good forum to monitor real-time outcome data. SUMMARY Biliary atresia continues to represent a major challenge with many unanswered questions. The establishment of multicentered collaboration in both basic science and clinical research interests has been an important step in improving outcomes for this disease.
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Petersen C, Harder D, Melter M, Becker T, Wasielewski RV, Leonhardt J, Ure BM. Postoperative high-dose steroids do not improve mid-term survival with native liver in biliary atresia. Am J Gastroenterol 2008; 103:712-9. [PMID: 18177447 DOI: 10.1111/j.1572-0241.2007.01721.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
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.
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Affiliation(s)
- Claus Petersen
- Department of Pedatric Surgery, Hannover Medical School, Hannover, Germany
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Abstract
BACKGROUND Postoperative cholangitis characterized by fever and acholic stool and positive blood culture is a common and serious complication following Kasai's operation for biliary atresia. The aim of this review was to describe the pathogenesis, clinical manifestations, medical treatment and outcome of postoperative cholangitis. DATA SOURCES Articles on biliary atresia retrieved from Pubmed and MEDLINE in the recent 10 years were reviewed. RESULTS The pathogenesis of postoperative cholangitis is still controversial. Recent methods for the diagnosis of postoperative cholangitis include urinary sulfated bile acids (USBA) and magnetic resonance cholangio-pancreaticography (MRCP). High-dose steroids and oral antibiotics have been used to reduce the incidence of postoperative cholangitis, and recurrent cholangitis leads to a lower survival rate. CONCLUSIONS Cholangitis is one of the most important determinants of long-term survival after the Kasai's procedure. The knowledge on postoperative cholangitis has been increasing in the past 10 years, showing a lower incidence of the disease and better therapeutic results.
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Affiliation(s)
- Yi Luo
- Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 200032, China
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Vejchapipat P, Passakonnirin R, Sookpotarom P, Chittmittrapap S, Poovorawan Y. High-dose steroids do not improve early outcome in biliary atresia. J Pediatr Surg 2007; 42:2102-2105. [PMID: 18082717 DOI: 10.1016/j.jpedsurg.2007.08.038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2007] [Accepted: 08/08/2007] [Indexed: 02/08/2023]
Abstract
PURPOSE Our objective was to evaluate the effects of steroids on early outcome in biliary atresia (BA). METHODS Patients with BA between 2001 and 2005 were reviewed. The use of steroids (4 mg/kg per day at alternate days for 1 to 3 months) has been routinely implemented since 2003. Jaundice-free status and the occurrence of cholangitis at 6 months postoperatively between patients receiving steroids and those not receiving steroids were compared. RESULTS Fifty-three patients with BA were studied. At 6 months postoperation, 30 patients (56.6%) were jaundice free and 24 patients (45.3%) experienced cholangitis at least once. Of the 53 patients, there were 33 patients in the steroid group and 20 patients in the nonsteroid group. The proportion of jaundice-free patients in the steroid group was higher than that in the nonsteroid group, and the proportion of patients with cholangitis in the steroid group was lower than that in the nonsteroid group. However, these discrepancies did not reach a statistically significant difference (jaundice-free status [steroid vs nonsteroid]: 20/33 [60.6%] vs 10/20 [50%], P = .57; cholangitis: 13/33 [39.4%] vs 11/20 [55%], P = .39). CONCLUSIONS Although the use of steroids seems to have benefits, it did not statistically improve early outcome in patients with BA.
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Affiliation(s)
- Paisarn Vejchapipat
- Department of Surgery, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
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Davenport M, Stringer MD, Tizzard SA, McClean P, Mieli-Vergani G, Hadzic N. Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia. Hepatology 2007; 46:1821-7. [PMID: 17935230 DOI: 10.1002/hep.21873] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
UNLABELLED The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post-Kasai portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with chi2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 micromol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 micromol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 micromol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22). CONCLUSION There was a beneficial effect on the rate of reduction of bilirubin in the early postoperative period (specifically in infants less than 70 days old at surgery), but this steroid regimen did not reduce the need for liver transplantation.
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Affiliation(s)
- Mark Davenport
- Department of Child Health, King's College London School of Medicine at King's College Hospital, London, United Kingdom.
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Affiliation(s)
- Ronald J. Sokol
- Pediatric Liver Center and Liver Transplantation Program Section of Pediatric Gastroenterology, Hepatology, and Nutrition University of Colorado School of Medicine The Children's Hospital Aurora, CO
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Stringer MD, Davison SM, Rajwal SR, McClean P. Kasai portoenterostomy: 12-year experience with a novel adjuvant therapy regimen. J Pediatr Surg 2007; 42:1324-8. [PMID: 17706489 DOI: 10.1016/j.jpedsurg.2007.03.026] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM The role of adjuvant therapy with corticosteroids and choleretics after Kasai portoenterostomy for biliary atresia (BA) remains uncertain. Experience with a novel postoperative adjuvant therapy regimen is reported. METHODS Between 1994 and 2006, 71 infants with BA were referred. Four died from uncorrectable congenital heart disease/cardiorespiratory failure without undergoing portoenterostomy, 7 underwent primary liver transplantation (3 referred > or = 19 weeks of age), and 60 underwent portoenterostomy at a median of 51 (10-104) days. Of these, 55 (92%) had type 3 BA and 6 had the BA splenic malformation syndrome. Fifty (83%) received the following adjuvant therapy beginning on postoperative day 5: oral dexamethasone 0.3 mg/kg bd for 5 days, 0.2 mg/kg bd for 5 days, and 0.1 mg/kg bd for 5 days together with oral ursodeoxycholic acid 5 mg/kg bd and phenobarbitone 5 mg/kg nocte, both of which were continued for 1 year. All infants received routine perioperative prophylactic antibiotics. RESULTS Overall, 42 of 60 (70%) infants cleared their jaundice (bilirubin < 20 micromol/L): 38 of 50 (76%) with the dexamethasone/ursodeoxycholic acid regimen compared with 4 of 10 (40%) not receiving this adjuvant treatment. There were 4 late deaths after portoenterostomy: 2 from associated congenital disorders and 2 after liver transplantation. Of the remaining 56 children, 39 (70%) are currently alive with their native liver at a median follow-up of 3.3 years and 17 are alive after liver transplantation. Surgical complications occurred in 3 after portoenterostomy: adhesive bowel obstruction (2) and an anastomotic leak. One infant had gastrointestinal bleeding that may have been related to dexamethasone, but this resolved with ranitidine. There were no perioperative septic complications. CONCLUSION In this series, adjuvant postoperative treatment with a short course of oral dexamethasone and longer-term ursodeoxycholic acid significantly improved the outcome after Kasai portoenterostomy.
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Abstract
Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region. Females are affected slightly more often than males. The common histopathological picture is one of inflammatory damage to the intra- and extrahepatic bile ducts with sclerosis and narrowing or even obliteration of the biliary tree. Untreated, this condition leads to cirrhosis and death within the first years of life. BA is not known to be a hereditary condition. No primary medical treatment is relevant for the management of BA. Once BA suspected, surgical intervention (Kasai portoenterostomy) should be performed as soon as possible as operations performed early in life is more likely to be successful. Liver transplantation may be needed later if the Kasai operation fails to restore the biliary flow or if cirrhotic complications occur. At present, approximately 90% of BA patients survive and the majority have normal quality of life.
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Affiliation(s)
- Christophe Chardot
- Service de chirurgie pédiatrique, Hôpital Cantonal Universitaire de Genève, Rue Willi Donzé 6, CH 1205 Geneve, Switzerland.
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Escobar MA, Jay CL, Brooks RM, West KW, Rescorla FJ, Molleston JP, Grosfeld JL. Effect of corticosteroid therapy on outcomes in biliary atresia after Kasai portoenterostomy. J Pediatr Surg 2006; 41:99-103; discussion 99-103. [PMID: 16410116 DOI: 10.1016/j.jpedsurg.2005.10.072] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
PURPOSE This study tests the hypothesis that steroid administration improves the outcome of biliary atresia (BA) by evaluating the efficacy of postoperative steroid use on surgical outcomes in infants with BA. METHODS Steroid use and outcomes in patients with BA were retrospectively analyzed at a tertiary pediatric hospital. Institutional review board approval was obtained. RESULTS Kasai portoenterostomy (PE) was performed in 43 patients with BA treated from 1992 to 2004 (16 boys and 27 girls). Twenty-one PE patients received steroids and 22 did not. Portoenterostomy was successful in 24 patients (55.8%) with consistent serum bilirubin less than 2 mg/dL. Sixteen (66%) received postoperative steroids. A normal postoperative bilirubin was achieved at 6 months in 16 (76%) of 21 patients with steroids compared with 8 (37%) of 22 in untreated controls (Fisher's Exact test, P = .01). Of the 43 patients, 19 (44%) required liver transplantation, including 7 (37%) of 19 with steroids vs 12 (63%) of 19 without (P = .2). Twenty-eight infants developed cholangitis (fever with and without changes in hepatic function): 25 after PE and 3 after transplant. Of the 25, 12 (48%) received steroids. Seven died (16%) (range, 7 months to 4 years): 2 while awaiting transplantation (received steroids) and 5 after transplantation (1 received steroids and 4 were untreated). Survival was 86% (18/21) in patients with steroids and 82% (18/22) in those without. Transplant survival (74%) was comparable to previously reported historical controls (82%). CONCLUSIONS The Kasai PE continues to be the procedure of choice in infants with BA younger than 3 months. A significantly improved clearance of postoperative jaundice and lower serum bilirubin levels were observed in patients receiving steroids. However, steroids had no effect on the incidence of cholangitis, need for liver transplantation, and overall survival. A prospective study with standardized dose and length of steroid administration and longer period of follow-up is necessary to more accurately assess the effectiveness of steroids after PE.
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Affiliation(s)
- Mauricio A Escobar
- Section of Pediatric Surgery, Department of Surgery, the JW Riley Hospital for Children, Indianapolis, IN 46202, USA
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Tatekawa Y, Muraji T, Tsugawa C. Glucocorticoid receptor alpha expression in the intrahepatic biliary epithelium and adjuvant steroid therapy in infants with biliary atresia. J Pediatr Surg 2005; 40:1574-80. [PMID: 16226987 DOI: 10.1016/j.jpedsurg.2005.06.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND/PURPOSE In patients with cirrhosis, proinflammatory cytokines increase progressively in relation to the severity of liver dysfunction. Proinflammatory cytokines regulate the expression of glucocorticoid receptors (GcRs). On the other hand, GcRs mediate the effects of glucocorticoid steroids on bile excretion in the biliary epithelium. Glucocorticoid receptors have 2 isoforms: a cytoplasmic glucocorticoid receptor alpha (GcRalpha) mediates their physiological effects, whereas a nuclear localized glucocorticoid receptor beta (GcRbeta) acts as a dominant negative inhibitor of GcRalpha activity. We examined the histology features of liver biopsy and the expression of GcRalpha in the intrahepatic biliary epithelium in infants with biliary atresia. PATIENTS/METHODS The patients were divided into 2 groups: patients in group 1 (n = 17) had a total bilirubin level below 1.0 mg/dL at least once after surgery, whereas patients in group 2 (n = 14) has never had bilirubin level below 1.0 mg/dL postoperatively. Liver biopsies taken from 31 infants with biliary atresia at the time of hepatic portoenterostomy between 1988 and 2002 were examined for immunohistochemistry and histology with H&E staining. The degree of GcRalpha expression in the biliary epithelium was semiquantitatively analyzed using staining scores. The histology features of the liver biopsy were also semiquantitatively analyzed by using the same scores to evaluate the liver injury. Intravenous prednisolone dosage was started with 4 mg/kg per day and tapered by a half dose every 2 days. The protocol was orally repeated during admission until the stool became constantly cholic. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient by rank. Significance is set at a 95% confidence interval (P < .05). RESULTS There was a significant positive correlation between the liver histology and the GcRalpha scores in all patients with biliary atresia (P = .0128; r = 0.429). In group 1, there was a significant positive correlation between the GcRalpha expression scores and the total dose of prednisolone administered (P = .0063; r = 0.767). CONCLUSIONS The increase and degree of GcRalpha expression were associated with the severity of liver injury and may correlate with the dose of prednisolone required to sustain bile flow after successful hepatic portoenterostomy.
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Affiliation(s)
- Yukihiro Tatekawa
- Division of Pediatric Surgery, Kobe Children's Hospital, Kobe 654-0081, Japan.
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Kobayashi H, Yamataka A, Koga H, Okazaki T, Tamura T, Urao M, Yanai T, Lane GJ, Miyano T. Optimum prednisolone usage in patients with biliary atresia postportoenterostomy. J Pediatr Surg 2005; 40:327-30. [PMID: 15750924 DOI: 10.1016/j.jpedsurg.2004.10.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
PURPOSE Prednisolone is used routinely after portoenterostomy (PE) in patients with biliary atresia (BA). The authors reviewed their patients with BA post-PE to assess prednisolone protocols. METHOD Severity of fibrosis at PE (moderate or severe), age at PE (30-70 days), size of bile ductules in the fibrotic biliary remnant at the porta hepatis (>100 microm), and type of BA (uncorrectable type) were used as criteria for selecting 63 subjects from our patients with BA post-PE. Subjects were divided into 5 groups according to prednisolone dosage: group 1, no prednisolone; groups 2 to 4, single courses of intravenous prednisolone commencing on day 7 post-PE administered in decreasing dose for 3 days each as follows: group 2, 6, 4, and 2 mg; group 3, 10, 5, and 2.5 mg; group 4, 20, 15, 10, 5, and 2.5 mg; group 5, same as group 4, but stool color was used to monitor bile excretion and a course was restarted from 20 mg whenever stools began to turn pale. If necessary, single courses were repeated until serum total bilirubin was less than 2.0 mg/dL. Protocol efficacy was assessed by comparing the number of patients who became jaundice free, the period taken to become jaundice free, and the incidence of side effects related to prednisolone. RESULTS The number of patients who became jaundice free in the no prednisolone group (group 1, 7/12 or 58.3%) was not significantly different from the number in the single-course groups (group 2, 8/12 or 66.6%; group 3, 10/13 or 76.9%; and group 4, 11/15 or 73.3%). The number in the stool-monitored group (group 5, 10/11 or 90.9%) was significantly greater (P < .05). The mean period taken to become jaundice free in group 1 (82.6 +/- 29.1 days) was not significantly different from the single-course groups (group 2, 74.5 +/- 29.3 days; group 3, 49.6 +/- 19.8 days; and group 4, 48.3 +/- 26.0 days). The mean period taken in the stool-monitored group (group 5, 33.3 +/- 6.4 days) was significantly shorter (P < .05). The number of subjects who developed cholangitis after becoming jaundice free was not significantly different (group 1, 2/7; group 2, 2/8; group 3, 2/10; group 4, 2/11; group 5, 2/10). There were no prednisolone-related complications identified in any subject. CONCLUSIONS These results provide strong evidence that large-dose prednisolone therapy with stool color monitoring of bile flow has a positive impact on the time taken for patients with BA post-PE to become jaundice free and the number of patients who remain jaundice free.
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Affiliation(s)
- Hiroyuki Kobayashi
- Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
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Muraji T, Nio M, Ohhama Y, Hashimoto T, Iwanaka T, Takamatsu H, Ohnuma N, Kato T, Ohi R. Postoperative corticosteroid therapy for bile drainage in biliary atresia--a nationwide survey. J Pediatr Surg 2004; 39:1803-5. [PMID: 15616935 DOI: 10.1016/j.jpedsurg.2004.08.019] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PURPOSE Members of the Japanese Biliary Atresia Society were surveyed to determine their current practice regarding early use of corticosteroids after Kasai's operation. METHODS Questions included the patient's background data, dosage, timing, complications, and outcome. Anicteric survival with the native liver was statistically compared between groups categorized by steroid dosage using Kaplan-Meier analysis. RESULTS Among 54 institutions surveyed, a total of 222 patients with uncorrectable BA were collected from 34 responders, including 208 patients who received steroid therapy and 14 without it. Prednisolone was started during the first postoperative week in 31% and during the second week in 64%. Perforation and peritonitis occurred in 1 patient given 3 mg/kg/d of prednisolone on postoperative day 1. The survival rates of the steroid and nonsteroid groups were 58.0% and 35.7%, respectively (P = .052). The initial dose of prednisolone was <or=3.9 mg/kg/d in 100 patients and >or=4.0 mg/kg/d in 108 patients. The survival rates of the group receiving >or=4.0 mg/kg/d and the nonsteroid group were 58.9% and 35.7%, respectively (P = .0494). CONCLUSIONS (1) Most surgeons use steroids. (2) Although the anicteric survival rate was higher in the steroid group, the number of patients in the nonsteroid group was too small to draw conclusions. (3) The recommended initial steroid dose is >or=4.0 mg/kg/d. (4) Complications are uncommon if administration is not started too early.
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Affiliation(s)
- Toshihiro Muraji
- Department of Pediatric Surgery, Kobe Children's Hospital, Hyogo-ken, Japan
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Hsieh CS, Huang CC, Huang LT, Tsai YJ, Chou MH, Chuang JH. Glucocorticoid treatment down-regulates chemokine expression of bacterial cholangitis in cholestatic rats. J Pediatr Surg 2004; 39:10-5. [PMID: 14694363 DOI: 10.1016/j.jpedsurg.2003.09.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Postoperative cholangitis is common after operation for biliary atresia. Empirical pulse therapy with glucocorticoid is effective in reversing some detrimental clinical manifestations, but the rationale for such a therapy still is not substantiated. METHODS Adult male rats were divided into groups according to the treatment: sterile normal saline (NS) or Escherichia coli (EC, 1 mL containing 10(8) cells of ATCC 25922 strain), 1 mL, were infused into the proximal choledochostomy (PC) tube 2 weeks after ligation of the PC tube (bile duct ligation, BDL), then immediate tube-tube choledocho-choledochostomy (biliary drainage, BD) was constructed. A high dose of dexamethasone (DEX, intraperitoneal injection; 2 mg/kg of body weight) was given after BD in treatment groups. Histopathology of the liver, as well as liver chemokine mRNA expression and serum chemokine levels, were studied 24 hours after treatment. RESULTS Inflammatory cell infiltration to the liver was retarded with DEX treatment, which was correlated with a significantly lower expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) mRNA in the liver (P =.006). Serum IL-8 and MCP-1 levels were also significantly down-regulated with DEX treatment (P = 0.008). CONCLUSIONS Glucocorticoid treatment is effective in modulating IL-8 and MCP-1 expression and ameliorating inflammatory cell infiltration in rat liver with bacterial cholangitis and cholestasis.
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Affiliation(s)
- Chih-Sung Hsieh
- Department of Pediatric Surgery, Chang Gung Memorial Hospital & Change Gung University, Naio-Sung Hsiang, Kaohsiung Hsien, Taiwan
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Affiliation(s)
- Ronald J Sokol
- Pediatric Liver Center and Liver Transplantation Program, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.
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Meyers RL, Book LS, O'Gorman MA, Jackson WD, Black RE, Johnson DG, Matlak ME. High-dose steroids, ursodeoxycholic acid, and chronic intravenous antibiotics improve bile flow after Kasai procedure in infants with biliary atresia. J Pediatr Surg 2003; 38:406-11. [PMID: 12632357 DOI: 10.1053/jpsu.2003.50069] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND/PURPOSE Early reports suggest that the use of steroids after Kasai portoenterostomy may improve bile flow and outcome in infants with biliary atresia. METHODS Of 28 infants with biliary atresia, half received adjuvant high-dose steroids, and half received standard therapy. Infants in the steroid group (n = 14) received intravenous solumedrol (taper of 10, 8, 6, 5, 4, 3, 2 mg/kg/d), followed by 8 to 12 weeks of prednisone (2 mg/kg/d). The steroid protocol also included ursodeoxycholic acid indefinitely and intravenous antibiotics for 8 to 12 weeks followed by oral antibiotic prophylaxis. Infants in the standard therapy group (n = 14) received no steroids, occasional ursodeoxycholic acid, and perioperative intravenous antibiotics followed by oral antibiotic prophylaxis. The infants were not assigned randomly, but rather received standard therapy or adjuvant steroid therapy according to individual surgeon preference. RESULTS Eleven of 14 (79%) in the steroid group and 3 of 14 (21%) in the standard therapy group had a conjugated bilirubin level less than 1.0 within 3 to 4 months of surgery (P <.001). Fewer patients in the steroid group (21% v 85%) required liver transplantation or died during the first year of life (P <.001). Infants in the steroid group did better despite the fact that this group included 5 infants with biliary atresia-polysplenia-heterotaxia syndrome, a subgroup that might have been expected to have a poor prognosis. Neither bile duct size nor liver histology was a reliable predictor of success or failure in either group. CONCLUSIONS Adjuvant therapy using high-dose steroids, ursodeoxycholic acid, and intravenous antibiotics may accelerate the clearance of jaundice and decrease the need for early liver transplantation after Kasai portoenterostomy.
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Affiliation(s)
- Rebecka L Meyers
- Divisions of Pediatric Surgery and Pediatric Gastroenterology, Primary Children's Medical Center, University of Utah School of Medicine, Salt Lake City, Utah 84113, USA
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Gupta DK, Charles AR, Srinivas M, Dave S, Bal CS. Betamethasone in plus phenobarbitone prior to hepatobiliary scintigraphy increases diagnostic accuracy in infants with jaundice. Indian J Pediatr 2001; 68:1039-41. [PMID: 11770238 DOI: 10.1007/bf02722353] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE In the diagnostic work up of the child with neonatal obstructive cholangiopathy (NOC), hepatobiliary scintigraphy (HBS) determines the need for peroperative cholangiography (POC). Traditionally, phenobarbitone is recommended to prime the liver to HBS. This retrospective study was designed to evaluate whether addition of the betamethasone (BM) alters the diagnostic accuracy of the HBS in distinguishing neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA). METHODS Between 1993-1999, 202 patients presented with NOC and this study was not designed as a prospective randomized clinical trial. Of these, 126 patients had received Phenobarbitone (Group I) and the remaining 76 (Group II) had received BM in addition to the PB in a dose of 5 mg/k/d and 2.2 mg/k/d respectively for 7 days prior to HBS. RESULTS Retrospective analysis revealed that, in the Group I, 41 showed excretion and 85 did not show any excretion of the radiopharmaceutical and the latter underwent POC which revealed that 31 patients (36%) of them showed patent biliary tract. In group II, 32 patients revealed excretion and 44 did not show any excretion of the radiopharmaceutical and the latter had undergone POC, which revealed that only 8 patients (18%) showed patent biliary tract. The percentages of false positives (36% vs 18%) was statistically significant (p < 0.03). CONCLUSION Addition of BM increases the diagnostic accuracy of the HBS and this would lead to decreased need for POC to distinguish NH from EHBA.
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Affiliation(s)
- D K Gupta
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India.
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Yamato Y, Kimura A, Murai T, Yoshimura T, Kurosawa T, Terazawa S, Takao A, Maeda K, Nakashima E, Yamashita Y, Kato H. 3beta-hydroxy-delta5 -C27-steroid dehydrogenase deficiency: diagnosis and treatment. J Paediatr Child Health 2001; 37:516-9. [PMID: 11885722 DOI: 10.1046/j.1440-1754.2001.00751.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The aim of this study was to evaluate the effects of bile acid treatment and to obtain further information about the pathway of bile acid biosynthesis in a patient with 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase (3beta-HSD) deficiency by gas chromatography-mass spectrometry. Results showed that at 2 months of age, 3beta-hydroxy-5-cholen-24-oic acid (3.0 micromol/mmol Cr, 7.9%) was detected in the urine in essentially the same relative amount as 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids (3.7 micromol/mmol Cr, 9.8%) during ursodeoxycholic acid treatment combined with prednisolone. As a result, diagnosis was delayed until 18 months of age. One month later with substitution of chenodeoxycholic acid treatment, urinary 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids decreased significantly, and subsequent improvement of liver dysfunction was accelerated. Chenodeoxycholic acid treatment is useful in 3beta-HSD deficiency. However, in the diagnosis of this disease in early life, it should be noted that the acidic pathway may be the major route for bile acid biosynthesis in the neonatal period. Diagnosis of 3beta-HSD deficiency may have been delayed by administration of ursodeoxycholic acid, resulting in prolonged diagnostic investigation in this child with cholestasis. Further, use of prednisolone may have been contraindicated.
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Affiliation(s)
- Y Yamato
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan
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Dillon PW, Owings E, Cilley R, Field D, Curnow A, Georgeson K. Immunosuppression as adjuvant therapy for biliary atresia. J Pediatr Surg 2001; 36:80-5. [PMID: 11150442 DOI: 10.1053/jpsu.2001.20013] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/PURPOSE Despite improvements in the surgical management of biliary atresia, the long-term incidence of progressive liver failure remains high. Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology, the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy. The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia. METHODS A retrospective analysis of all patients with biliary atresia treated with an hepatoportoenterostomy and postoperative steroid therapy at our 3 institutions was undertaken. Patients were treated uniformly with immunosuppressive doses of oral steroids for a minimum of 6 weeks after surgery. RESULTS Twenty-five infants with biliary atresia were treated with steroid therapy. Overall survival rate was 22 patients (88%) with a mean follow-up period of 50 months. Nineteen patients (76%) became jaundice free with native liver function. Four patients (16%) did not respond to treatment and required transplantation. Age less than 12 weeks was a crucial predictor of success of adjuvant steroid therapy. Cholangitis developed in 8 patients (32%). There were no complications caused by steroid therapy. CONCLUSIONS Steroid administration at immunosuppressive doses markedly improves the clinical outcome within the first 5 years after surgery as measured by jaundice-free status and survival without liver transplantation when compared with concurrent reports. These results suggest that immunosuppressive therapy is safe and has a positive impact on the clinical course of this disease. However, a randomized study is needed to ultimately prove such an hypothesis.
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Affiliation(s)
- P W Dillon
- Division of Pediatric Surgery, Department of Surgery, Children's Hospital, Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershey, PA, USA
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45
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Abstract
Controversy exists regarding the efficacy of corticosteroids on bile flow after Kasai portoenterostomy in biliary atresia (BA). Fourteen patients who had BA and underwent Kasai portojejunostomy between November 1990 and March 1996 were subject of this study. Corticosteroid therapy ("blast" type) was used for inadequate bile drainage. Corticosteroid support was unnecessary in one patient with good bile drainage, and corticosteroids were aggressively used in the remaining 13 patients. Two patients who had no response to an initial blast subsequently responded and now are doing well. The remaining 11 patients responded to corticosteroids with varying degrees. Three had a limited response, and two ultimately underwent liver transplantation. There was one death caused by subdural hematoma. Three had an excellent initial response. However, one subsequently deteriorated because of intractable cholangitis, requiring liver transplantation. Ten survivors with native liver are anicteric with satisfactory growth and quality of life. Aggressive corticosteroid therapy is an important part of the management after Kasai portoenterostomy. The initial response to steroids does not necessarily reflect the final outcome.
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Affiliation(s)
- T Muraji
- Department of Surgery, Kobe Children's Hospital, Sumaku, Japan
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Muraji T, Nishijima E, Higashimoto Y, Tsugawa C. Biliary atresia: current management and outcome. TOHOKU J EXP MED 1997; 181:155-60. [PMID: 9149350 DOI: 10.1620/tjem.181.155] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Between 1986 and 1994, 42 patients with BA were treated at the Kobe Children's Hospital. These patients underwent a wider excision of the hilar fibrous remnant with Roux-Y reconstruction (with or without intussuscepted valve) without stoma. Corticosteroids were used postoperatively when the stool was acholic or unsteadily cholic. The daily dose was reduced from 20 mg/day by half down. The patients were divided into two groups; in Group I (n = 17, before October 1990), a single course of corticosteroid therapy was employed. In Group II (n = 25, from November 1990 on), this regimen was repeated whenever the stool appeared less cholic. The bile flow improved significantly (excellent in 29% and 60%, and poor in 71% and 32% in Groups I and II, respectively.) Corticosteroids were used in 15 Group I patients with good response in 10 and in 21 Group II patients, 15 of whom had multiple courses. Sixteen of the 21 Group II patients had a good response. The incidence of the cholangitis was not significantly different between the 19 patients with valve and the 23 patients without valve. A 5 year survival significantly improved from 70% in Group I to 96% in Group II. In both groups, the survival rate significantly increased, when compared with the survival rate figured out with an assumption of OLT survivors as dead. On the same assumption, the survival rate of Group II is significantly more than that of the Group II. These suggest a positive contribution of liver transplantation and an aggressive corticosteroid therapy on better survival of Group II.
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Affiliation(s)
- T Muraji
- Department of Surgery, Kobe Children's Hospital, Japan
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Sartorelli KH, Holland RM, Allshouse MJ, Karrer FM, Lilly JR. The intussusception antireflux valve is ineffective in preventing cholangitis in biliary atresia. J Pediatr Surg 1996; 31:403-6. [PMID: 8708912 DOI: 10.1016/s0022-3468(96)90747-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Cholangitis is the most common complication after portoenterostomy for biliary atresia. The construction of an intussusception valve in the Roux-en-Y limb of the portoenterostomy has been advocated as a means to ameliorate this complication. The authors reviewed the records of children who underwent portoenterostomy to assess the incidence and severity of cholangitis, as well as outcome. The children were divided into two groups according to whether they did not have (group I) or did have (group II) an antireflux valve in the Roux limb of the bilioenteric conduit. There were 19 children in each group. There were no significant differences between the groups with respect to age at time of portoenterostomy or length of follow-up (Table 1). Nine group I patients are alive and well; five died and five have had or are awaiting transplantation. In group II, 10 patients are alive and well, eight have had transplantation, and one is awaiting transplantation. Outcome with respect to death or the need for liver transplantation because of progressive hepatic failure is not different between the groups (P = 1.0, Fisher's 2 x 2). The incidence of cholangitis was evaluated by comparing the average number of episodes of cholangitis during the follow-up period, the number of episodes per year, and the number of episodes in the first postoperative year (when this complication is most prevalent). Analysis of the data showed no difference in incidence between those with valved and nonvalved biliary conduits. The severity of cholangitis, judged by total length of antibiotic treatment, did not differ between the groups. It appears that the presence of an intussusception valve in the Roux-en-Y biliary conduit does not affect the incidence of cholangitis or the outcome after portoenterostomy, over short-term follow-up.
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Affiliation(s)
- K H Sartorelli
- Department of Surgery, University of Colorado School of Medicine, Denver, USA
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Tagge DU, Tagge EP, Drongowski RA, Oldham KT, Coran AG. A long-term experience with biliary atresia. Reassessment of prognostic factors. Ann Surg 1991; 214:590-8. [PMID: 1953112 PMCID: PMC1358615 DOI: 10.1097/00000658-199111000-00009] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Thirty-four infants with biliary atresia were primarily treated at our institution between 1974 and 1987. The mean age at diagnosis was 8.8 weeks. The Kasai portoenterostomy was used in 11 patients (32%) and the Sawaguchi modification in 23 infants (68%). Overall survival was 47% (16/34), with a mean follow-up of 45 months. Fifteen survivors (94%) are jaundice free, with two having undergone liver transplantation. Survival was not influenced by earlier age at operation, size of ductal remnants, or the use of an external biliary vent. Good bile flow was predictive of a favorable outcome. The incidence of cholangitis was increased in the Kasai (87%) versus the Sawaguchi groups (45%) (p less than 0.05), but 1-year survival rates were similar (55% vs 64%). The authors conclude that portoenterostomy offers a reasonable chance for success and should be the initial procedure for biliary atresia.
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Affiliation(s)
- D U Tagge
- Department of Surgery, Mott Children's Hospital, University of Michigan Medical School, Ann Arbor
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49
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Abstract
Jaundice in the pediatric patient requires prompt and directed evaluation. This dictum is highlighted in infants with biliary atresia, in whom the progressive sclerosing process results in complete obliteration of patent but microscopic hilar biliary structures by 4 months of age. Kasai's operation, if done before that time, will re-establish bile drainage in 90% of infants. One fourth to one third of patients achieve long-term jaundice-free survival. Complications of cholangitis, portal hypertension, and fat malabsorption are experienced by many patients. In children with early or late operative failure, liver replacement now offers legitimate hope for extended survival. Choledochal cyst is a conglomerate of pancreaticobiliary anomalies consisting of a choledochal cyst, a common-channel-type pancreaticobiliary junction, intrahepatic cystic disease, and partial obstruction of the distal common bile duct. Many patients have one or more of these malformations. It is now widely accepted that the preferred treatment of choledochal cyst is total excision of the diseased biliary duct with reconstruction by Roux-en-Y choledochojejunostomy. "Internal" excision avoids injury to other structures in the hepatoduodenal ligament, particularly if pericystic inflammation is present. Congenital perforation of the common bile duct responds in most cases to simple peritoneal drainage of the perforation. Retention of the tube cholecystostomy is useful for subsequent cholangiographic follow-up. Tube cholecystostomy may also be useful for irrigation of the biliary tract in infants with inspissated bile syndrome.
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Affiliation(s)
- F M Karrer
- Department of Surgery, Children's Hospital, Denver, Colorado
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50
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Lilly JR, Karrer FM, Hall RJ, Stellin GP, Vasquez-Estevez JJ, Greenholz SK, Wanek EA, Schroter GP. The surgery of biliary atresia. Ann Surg 1989; 210:289-94; discussion 294-6. [PMID: 2673083 PMCID: PMC1357988 DOI: 10.1097/00000658-198909000-00004] [Citation(s) in RCA: 60] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
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).
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Affiliation(s)
- J R Lilly
- Department of Surgery, University of Colorado School of Medicine, Denver 80262
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