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Liu SH, Chen CC, Chao HC, Kong MS, Lai JY, Lai MW. Annual cholangitis more than twice predicts liver transplant in biliary atresia patients who achieve jaundice-free after Kasai portoenterostomy. J Formos Med Assoc 2025:S0929-6646(25)00006-3. [PMID: 39818465 DOI: 10.1016/j.jfma.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 11/29/2024] [Accepted: 01/06/2025] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Biliary atresia (BA) is a progressive liver disease even after Kasai portoenterostomy (KPE), and the most common cause of liver transplant (LT) in the pediatric population. This study aimed to unveil the risk factors for LT in BA patients post-KPE. METHODS We conducted a retrospective study of BA patients in a northern Taiwan Children's Medical Center from Jan 2000 to Oct 2020. RESULTS A total of 65 BA patients (32 males, 33 females) were included. Seventeen (26%) patients received LT. Multivariate analysis showed higher serum direct bilirubin (cutoff ≥1.1 mg/dL) 3 months post-KPE (OR 8.17, p = 0.037) and higher peak yearly cholangitis episodes (OR 3.32, p = 0.008) independently predicted LT. In patients achieving jaundice-free (JF), yearly cholangitis frequency (OR 2.64, p = 0.032) independently predicted LT (cutoff ≥3). Concerning high cholangitis frequency, the independent predictor was the first cholangitis occurring 61-120 days post-KPE (OR 6.61, p = 0.034). In patients who achieved JF, bacteremia (OR 20.06, p = 0.037) and higher AST level 6 months post-KPE (OR 1.02, p = 0.016) independently predicted higher peak annual cholangitis frequency. CONCLUSIONS Higher direct bilirubin 3 months post-KPE (≥1.1 mg/dL) and higher peak annual cholangitis frequency predict LT in BA patients. The first cholangitis occurring 61-120 days post-KPE predicts higher peak annual cholangitis frequency. In patients who achieved JF, peak annual cholangitis episodes with a threshold of ≥3 independently predict LT. Bacteremia and higher serum AST levels at six months post-KPE predict higher peak annual cholangitis frequency.
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Affiliation(s)
- Su-Han Liu
- Division of Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
| | - Chien-Chang Chen
- Division of Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan; Chang Gung University College of Medicine, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan
| | - Hsun-Chin Chao
- Division of Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan; Chang Gung University College of Medicine, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan
| | - Man-Shan Kong
- Division of Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan
| | - Jin-Yao Lai
- Department of Pediatric Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan; Chang Gung University College of Medicine, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan
| | - Ming-Wei Lai
- Division of Gastroenterology, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan City 33305, Taiwan; Liver Research Center, Linkou Chang Gung Memorial Hospital, No.5, Fuxing St., Guishan Dist., Taoyuan City, 33305, Taiwan; Chang Gung University College of Medicine, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan.
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Nyholm I, Hukkinen M, Pakarinen MP. Predicting and managing liver fibrosis in biliary atresia. Semin Pediatr Surg 2024; 33:151473. [PMID: 39884181 DOI: 10.1016/j.sempedsurg.2025.151473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/07/2025] [Indexed: 02/01/2025]
Abstract
Regardless of the underlying etiology and success of PE, progressive liver fibrosis and eventually cirrhosis represent the dominant pathology and the end-stage of BA. Ascending bile duct injury-induced cholestasis, inflammation and ductular reaction provide profibrogenic cytokine environment leading to myofibroblast activation and rapid progression of fibrosis especially after unsuccessful portoenterostomy. Although liver fibrosis and development of cirrhosis play a crucial role in determining BA outcomes, the exact prognostic significance and dynamics of mild to moderate liver fibrosis remain unclear. Manual scoring systems categorizing the degree of liver fibrosis are prone to intra- and interobserver variability, whereas novel combinations of digital pathology with artificial intelligence quantification can provide accurate information on fibrosis structure and dynamics at the level of individual collagen fibers. Although several studies have analyzed noninvasive assessment of fibrosis at time of PE, including imaging-based elastography and different serum biomarkers, current knowledge on their accuracy during the postoperative follow-up of BA is scarce. While therapeutic management of liver fibrosis in BA remains in its infancy, the resolution potential for liver fibrosis has been demonstrated after successful PE. Achievement of effective antifibrotic treatment may require combination of different therapies with complementary modes of action like anti-inflammatory medication, antioxidants and bile acid lowering agents.
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Affiliation(s)
- Iiris Nyholm
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Maria Hukkinen
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mikko P Pakarinen
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
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3
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Shan L, Wang F, Zhai D, Meng X, Liu J, Lv X. Kasai Portoenterostomy, Successful Liver Transplantation, and Immunosuppressive Therapy for Biliary Atresia in a Female Baby: A Case Report. J Inflamm Res 2024; 17:4905-4920. [PMID: 39070130 PMCID: PMC11283245 DOI: 10.2147/jir.s432024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 07/17/2024] [Indexed: 07/30/2024] Open
Abstract
Background Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%-80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation. Case Summary Here, we report a case of a newborn female baby (birthday: 10-03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father's liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal. Conclusion This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province.
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Affiliation(s)
- Liang Shan
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Fengling Wang
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China
| | - Dandan Zhai
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China
| | - Xiangyun Meng
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China
| | - Jianjun Liu
- Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China
| | - Xiongwen Lv
- Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China
- The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China
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Tam PKH, Wells RG, Tang CSM, Lui VCH, Hukkinen M, Luque CD, De Coppi P, Mack CL, Pakarinen M, Davenport M. Biliary atresia. Nat Rev Dis Primers 2024; 10:47. [PMID: 38992031 PMCID: PMC11956545 DOI: 10.1038/s41572-024-00533-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/10/2024] [Indexed: 07/13/2024]
Abstract
Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000-20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50-75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60-75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.
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Affiliation(s)
- Paul K H Tam
- Medical Sciences Division, Macau University of Science and Technology, Macau, China.
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
| | - Rebecca G Wells
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Clara S M Tang
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China
| | - Vincent C H Lui
- Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong SAR, China
| | - Maria Hukkinen
- Section of Paediatric Surgery, Paediatric Liver and Gut Research Group, New Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Carlos D Luque
- Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina
| | - Paolo De Coppi
- NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Cara L Mack
- Department of Paediatrics, Division of Paediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI, USA
| | - Mikko Pakarinen
- Section of Paediatric Surgery, Paediatric Liver and Gut Research Group, New Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden
| | - Mark Davenport
- Department of Paediatric Surgery, King's College Hospital, London, UK
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Kawaguchi Y, Terui K, Takenouchi A, Komatsu S, Saito T, Hishiki T. Outcomes of adult native liver survivors with biliary atresia: the current situation in Japan. Pediatr Surg Int 2023; 39:263. [PMID: 37668658 DOI: 10.1007/s00383-023-05551-6] [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] [Accepted: 08/25/2023] [Indexed: 09/06/2023]
Abstract
PURPOSE This study aimed to elucidate the difficulties faced by adult native liver survivors with biliary atresia (BA) in Japan. METHODS A single-center, retrospective, observational study of 57 adult patients with BA was conducted. The clinical course of BA was compared between native liver survivors and non-survivors who reached adulthood. Indications and outcomes of liver transplantation (LT) among non-survivors were assessed. RESULTS A significantly larger portion of non-survivors (n = 10) met the criteria for LT (p < 0.001) and received treatment for portal hypertension after reaching 20 years of age (p < 0.01) compared with the survivors. Causes of death included liver cirrhosis (n = 8), graft failure of living donor liver transplantation (LDLT) (n = 1), and hepatocarcinoma (n = 1). Two of the non-survivors who died of liver cirrhosis had no indication for LT because of alcohol dependence and uncontrolled infection. An appropriate donor candidate could not be found for the five patients who opted for LDLT. All six patients waitlisted for deceased donor liver transplantation (DDLT) died after a median waiting period of 17 months. CONCLUSION Adult BA patients in Japan have limited options for LT, mainly owing to low donor candidate availability for LDLT and a low prevalence of DDLT.
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Affiliation(s)
- Yunosuke Kawaguchi
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
| | - Keita Terui
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
| | - Ayako Takenouchi
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
| | - Shugo Komatsu
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
| | - Takeshi Saito
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
- Department of Pediatric Surgery, Chiba Children's Hospital, 579-1 Heta-Cho, Midori-ku, Chiba, Japan
| | - Tomoro Hishiki
- Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
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Vimalesvaran S, Samyn M, Dhawan A. Liver disease in adolescents. Arch Dis Child 2023; 108:427-432. [PMID: 36167480 DOI: 10.1136/archdischild-2021-323647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 09/19/2022] [Indexed: 11/04/2022]
Abstract
In this article, we discuss common liver diseases in the adolescent population. We describe the initial evaluation of an adolescent presenting with new-onset liver enzyme abnormalities, based on the clinical history and physical examination. The management approach to the adolescent with liver disease is exemplified, including monitoring for adherence, risk-taking behaviours and focusing on psychosocial aspects of their care. Finally, we highlight the challenges of caring for the adolescent patient and the importance of addressing not only the liver disease but, more importantly, the holistic approach towards their management.
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Affiliation(s)
- Sunitha Vimalesvaran
- Paediatric Liver, Gastroenterology and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, UK
| | - Marianne Samyn
- Paediatric Liver, Gastroenterology and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, UK
| | - Anil Dhawan
- Paediatric Liver, Gastroenterology and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, UK
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7
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Nyholm I, Hukkinen M, Pihlajoki M, Davidson JR, Tyraskis A, Lohi J, Heikkilä P, Hänninen S, Andersson N, Eloranta K, Carpén O, Heikinheimo M, Davenport M, Pakarinen MP. Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia. Hepatology 2023; 77:1263-1273. [PMID: 36692476 PMCID: PMC10026978 DOI: 10.1097/hep.0000000000000048] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 11/08/2022] [Accepted: 11/11/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND AND AIMS Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. APPROACH AND RESULTS Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19 , and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p <0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p =0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p =0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p <0.001) also among patients operated <60 days of age (HR: 8.77, p =0.004) or after successful KPE (HR: 6.76, p =0.01). Serum FGF19 correlated positively with increased serum primary bile acids ( R =0.41, p =0.004) and ductular reaction ( R =0.39, p =0.004). CONCLUSIONS Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction.
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Affiliation(s)
- Iiris Nyholm
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Maria Hukkinen
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Marjut Pihlajoki
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Joseph R. Davidson
- Department of Pediatric Surgery, GOS-UCL Institute of Child Health, London, UK
- Department of Pediatric Surgery, King’s College Hospital, London, UK
| | | | - Jouko Lohi
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Päivi Heikkilä
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Satu Hänninen
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Noora Andersson
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Katja Eloranta
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Olli Carpén
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Markku Heikinheimo
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Pediatrics, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, Missouri, USA
| | - Mark Davenport
- Department of Pediatric Surgery, King’s College Hospital, London, UK
| | - Mikko P. Pakarinen
- Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden
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Le M, Reinshagen K, Tomuschat C. Systematic review: The quality of life of patients with biliary atresia. J Pediatr Surg 2022; 57:934-946. [PMID: 35428492 DOI: 10.1016/j.jpedsurg.2022.03.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/22/2022] [Accepted: 03/13/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND The quality of life of patients with Biliary Atresia (BA) have not been systematically examined. The goal of this meta-analysis is to determine patients' postoperative health-related Quality of life (HrQoL) with native or transplanted livers. METHODS From 2000 to August 2021, a literature-based search for relevant cohorts was conducted using Pubmed/Medline, the Cochrane Library, and Embase. Original research on BA, Hepatoportoenterostomy (HPE), portoenterostomy, Kasai, Liver transplantation and HrQoL was included. Using RevMan, a forest plot analysis of HrQoL after surgical treatment after BA was calculated (version 5.4). Using MetaXL, a pooled prevalence for cholangitis, secondary liver transplantation, or related malformations was computed (version 5.3). RESULTS Nine studies compared individuals with BA to an age-matched healthy control group. 4/9 (n = 352) of these studies found poorer scores for BA patients, while 5/9 (n = 81) found equivalent health status. Factors associated with HrQoL: older age at the time of the survey was linked to greater HrQoL; whereas females, higher total bilirubin and the amount of immunosuppressive medicines were associated with lower HrQoL in BA patients. CONCLUSION The current study emphasises the critical need to improve the many parameters influencing HrQoL in BA patients, as well as the methods utilized to assess those factors. This includes immunosuppression, withdrawal from polydrug regimes and recognizing the differences in disease burden between males and females. TYPE OF STUDY Systematic review. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Melanie Le
- Department of Pediatric Surgery, Kinder-UKE Campus Ost 45, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany
| | - Konrad Reinshagen
- Department of Pediatric Surgery, Kinder-UKE Campus Ost 45, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany
| | - Christian Tomuschat
- Department of Pediatric Surgery, Kinder-UKE Campus Ost 45, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
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Tsuboi K, Watayo H, Tsukui T, Suda K, Abe E, Fujimoto T, Ochi T, Lane GJ, Koga H, Yamataka A. Native liver survivors of portoenterostomy for biliary atresia with excellent outcome: redefining "successful" portoenterostomy. Pediatr Surg Int 2022; 39:24. [PMID: 36454515 DOI: 10.1007/s00383-022-05313-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 12/03/2022]
Abstract
PURPOSE Native liver survivors (NLS) after portoenterostomy (PE) for biliary atresia (BA) with normal biomarkers defined as total bilirubin (T-Bil), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) for liver function (LF), cholinesterase (ChE), platelet count (PC), and absence of portal hypertension (PHT) were reviewed to redefine "successful" PE. METHODS 92 post-PE BA patients were classified as NLS-1: normal biomarkers, PHT (-); NLS-2: at least one abnormal biomarker, PHT (-); NLS-3: normal biomarkers, PHT ( +); NLS-4: abnormal biomarkers, PHT ( +) and reviewed for a maximum 32 years. RESULTS As of June 2022, 55/92 (59.8%) had received liver transplants and 37/92 (40.2%) were NLS. NLS patients were classified as excellent outcome (EO): NLS-1 (n = 10; 27.0%) or non-EO: NLS-2: (n = 8; 21.6%), NLS-3: (n = 6; 16.2%), and NLS-4: (n = 13; 35.1%). Compared with non-EO, EO had PE earlier (50.5 versus 65 days; not significant; p = 0.08), significantly earlier onset of symptoms (13 days versus 32 days; p = 0.01) and significantly shorter jaundice-clearance (JC; 34.5 days versus 56.0 days; p < 0.001). Durations of follow-up were similar: 13 years in EO, 18.5 years in NLS-2, 20 years in NLS-3, and 15 years in NLS-4. CONCLUSION Incidence of "successful" PE or EO is low and correlated with early onset of symptoms and quicker JC.
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Affiliation(s)
- Koichi Tsuboi
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Hiroko Watayo
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Takafumi Tsukui
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Kazuto Suda
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Eri Abe
- Department of Pediatric Surgery, Juntendo Urayasu Hospital, Chiba, Japan
| | - Takamori Fujimoto
- Department of Pediatric Surgery, Juntendo Nerima Hospital, Tokyo, Japan
| | - Takanori Ochi
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Geoffrey J Lane
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hiroyuki Koga
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Atsuyuki Yamataka
- Department of Pediatric Surgery, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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Zheng L, Wu Y, Gong Z, Lv Z, Xu W, Sheng Q, Huang X, Liu J. The composition of the gut microbiota is altered in biliary atresia with cholangitis. Front Surg 2022; 9:990101. [PMID: 36338646 PMCID: PMC9632985 DOI: 10.3389/fsurg.2022.990101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 09/05/2022] [Indexed: 12/02/2022] Open
Abstract
Aim To detect the composition of the gut microbiota in biliary atresia after Kasai surgery. Methods Infants within six months after the Kasai operation who were diagnosed by cholangiography at Shanghai Children’s Hospital were enrolled in the study. Fecal samples were collected from diapers, placed into sterile tubes in the inpatient department or outpatient department and frozen at −80°C within half an hour. The gut microbiota was detected by 16S rRNA sequences. Then, the patients that were followed up to one year after the Kasai operation who suffered from cholangitis at least one time were grouped into the BAcho group, and the others were grouped into the BAnoncho group. Results Nine of 18 BA patients were grouped into the BAcho group, and the others were grouped into the BAnoncho group. In the BAcho group, AST, ALT and GGT were significantly increased compared to the BAnoncho group. The number of total OTUs (operational taxonomic units) in feces was more elevated in the BAnoncho group than in the BAcho group. In the BAnoncho group, the Chao index at the OTU level was significantly increased compared to that in the BAcho group (66.37 ± 21.5 vs. 45.64 ± 11.25, p = 0.02 < 0.05). Bifidobacterium was the most abundant genus in the BAnoncho group, accounting for 22.14%, and Klebsiella accounted for 22.74% in the BAcho group. Compared with the BAnoncho group, Bacteroides was significantly decreased in the BAcho group (p = 0.037). Conclusion The composition of the gut microbiota was different between BA with cholangitis and BA without cholangitis.
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11
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Madadi-Sanjani O, Fortmann D, Rolle U, Rodeck B, Sturm E, Pfister ED, Kuebler JF, Baumann U, Schmittenbecher P, Petersen C. Centralization of Biliary Atresia: Has Germany Learned Its Lessons? Eur J Pediatr Surg 2022; 32:233-239. [PMID: 33663007 DOI: 10.1055/s-0041-1723994] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. MATERIALS AND METHODS In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. RESULT Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001-2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001-2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001-2005 [p = 0.5]). Compared with the 2001-2005 analysis, all criteria showed improvement but the differences are statistically not significant. CONCLUSION Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.
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Affiliation(s)
| | - David Fortmann
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - Udo Rolle
- Department of Pediatric Surgery and Pediatric Urology, Goethe University Frankfurt /M., Germany
| | - Burkhard Rodeck
- Department of Pediatric Gastroenterology, Christliches Kinderhospital Osnabrueck, Osnabrueck, Germany
| | - Ekkehard Sturm
- Department of Paediatric Gastroenterology and Hepatology, University Hospital for Children and Adolescents, University of Tuebingen, Baden-Württemberg, Germany
| | - Eva-Doreen Pfister
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Joachim F Kuebler
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - Ulrich Baumann
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
- Liver Unit, Birmingham Women's and Children's Hospital, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham
| | - Peter Schmittenbecher
- Department of Pediatric Surgery, Municipal Hospital, Karlsruhe, Baden-Wuerttemberg, Germany
| | - Claus Petersen
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
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12
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Alexander EC, Greaves W, Vaidya HJ, Burford C, Jain V, Samyn M. Social and Educational Outcomes in Patients With Biliary Atresia: A Systematic Review. J Pediatr Gastroenterol Nutr 2022; 74:104-109. [PMID: 34560722 DOI: 10.1097/mpg.0000000000003306] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVES To systematically review the social outcomes of patients with biliary atresia (BA), including educational, employment and family outcomes. METHODS We conducted a systematic review of Medline, EMBASE, Global Health, Maternity and Infant Care Database, supplemented by reference searching. National Heart, Lung and Blood Institute scoring was conducted for quality assessment. The PROSPERO registration ID was CRD42020178846. RESULTS Fifty-one studies were included (41 cohort, 10 cross-sectional), including 4631 participants across 16 countries. Cohorts were BA post-liver transplant (LT) (18 studies), native liver survivors (NLS) (16 studies), mixed (13 studies) and four other cohorts. Outcomes covered; education (n = 35), employment (n = 16), family outcomes (n = 22), and social functioning (n = 22). BA patients had lower school functioning scores than controls, with no difference between NLS versus post-LT. Between 2% and 48% of children required additional educational support. Between 60% and 100% of adult patients with BA were employed. Pregnancies were described in 17 studies, with small samples, and some noted complications. Social functioning scores were similar to healthy controls in 8 of 11 comparisons. CONCLUSIONS Despite BA being the primary indication for liver transplantation in childhood, social outcomes for children and adolescents are predominantly reported in non-controlled, single-centre survey-based studies. School functioning is lower compared to peer groups, with no evidence of a difference for those having a liver transplant. We recommend routine psychosocial assessment of these patients during follow-up, alongside multi-centre collaborations, to maximise the quality of evidence for future patients.
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Affiliation(s)
- Emma C Alexander
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital
- William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London
| | - William Greaves
- University College London Medical School, University College London
- Northwick Park Hospital, London North West University Healthcare NHS Trust, London
| | - Hrisheekesh J Vaidya
- Northwick Park Hospital, London North West University Healthcare NHS Trust, London
| | - Charlotte Burford
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital
- William Harvey Hospital, East Kent University Hospitals NHS Foundation Trust, Ashford, UK
| | - Vandana Jain
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital
| | - Marianne Samyn
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital
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Al-Hussaini A, Abanemai M, Alhebbi H, Saadah O, Bader R, Al Sarkhy A, Alhatlani M, Halabi H, Aladsani A, AlEdreesi M, Wali S, Alguofi T, Al-Drees K, Arain Z, Al Saleem B, Asery A, Holdar S, Alrashidi S, Alsayed F, Aldhalan S, NasserAllah A, Alghamdi R, Alhaffaf F, AlAwfi A, AlSweed A, Alshamrani A, AlShaikh M, Saeed A, Assiri H, Bashir MS. The Epidemiology and Outcome of Biliary Atresia: Saudi Arabian National Study (2000-2018). Front Pediatr 2022; 10:921948. [PMID: 35923790 PMCID: PMC9339784 DOI: 10.3389/fped.2022.921948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 05/27/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The epidemiology and outcomes of biliary atresia (BA) have been well-documented in national cohorts from two main ethnicities, namely, the Asian Orientals and Caucasians, with incidence ranging from 1 in 5,000 to 1 in 9,000 live births in East Asia and 1 in 15,000 to 19,000 live births in Europe and North America. OBJECTIVE We report the first nationwide BA study outside North America, Europe, and East Asia to describe the epidemiology and outcomes of BA in Saudi Arabia. METHODS A national database of BA cases diagnosed between 2000 and 2018 was analyzed. We assessed clearance of jaundice (bilirubin <20 μmol/L) in all cases that underwent Kasai portoenterostomy (KPE). We then estimated survival using the Kaplan-Meier method with endpoints of liver transplantation (LT), death, or survival with native liver (SNL). RESULTS BA was diagnosed in 204 infants (106 females; 10% pre-term). The incidence of BA was 1 in 44,365, or 2.254 in 100,000 live births (range, 0.5-4 in 100,000). Polysplenia was diagnosed in 22 cases (11%). The median age at referral was 65 days. A total of 146 children (71.5%) underwent KPE at a median age of 70 days. Clearance of jaundice was achieved in 66 of the 146 (45%) infants. The 10-year SNL after KPE was 25.5%, and the overall 10-year estimated survival was 72.5%. The Kaplan-Meier survival curves for patients undergoing KPE at the age of <60, 61-90, and >90 days showed a SNL rate at 51.6, 33, and 12.5%, respectively, at 5 years (P < 0.001). The 2-, 5-, and 10-year post-LT survival rates were 92.5, 90.6, and 90%, respectively. Undergoing an initial KPE did not impact negatively on the overall LT survival rate when compared to BA cases that underwent primary LT (P = 0.88). CONCLUSION The incidence rate of BA in Saudi Arabia is lower than the incidence reported elsewhere. Late referral of BA cases remains a problem in Saudi Arabia; as a result, the SNL rate was lower than reported by other national registries. Hence, national policies devoted to timely referral and earlier age at KPE are needed.
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Affiliation(s)
- Abdulrahman Al-Hussaini
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.,College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.,Prince Abdullah Bin Khaled Celiac Disease Research Chair, Department of Pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammed Abanemai
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Homoud Alhebbi
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Omar Saadah
- Division of Pediatric Gastroenterology, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Razan Bader
- Multi-Organ Transplant Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.,King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Ahmed Al Sarkhy
- Gastroenterology Division, Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Maher Alhatlani
- Al Imam Abdulrahman Bin Faisal Hospital, Ministry of National Guard Health Affairs, Dammam, Saudi Arabia
| | - Hana Halabi
- Maternity and Children's Hospital, Makkah, Saudi Arabia
| | - Ahmed Aladsani
- Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed AlEdreesi
- Specialty Pediatrics Division, Women and Children's Health Institute, Pediatric Gastroenterology, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Sami Wali
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Talal Alguofi
- Organs Transplant Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Khalid Al-Drees
- Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Zahid Arain
- Multi-Organ Transplant Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.,King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Badr Al Saleem
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ali Asery
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Sinan Holdar
- Division of Pediatric Gastroenterology, Department of Pediatrics, Royal Commission Hospital, Jubail, Saudi Arabia
| | - Sami Alrashidi
- Division of Pediatric Gastroenterology, Children's Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Fahad Alsayed
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Sulaiman Aldhalan
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Rawabi Alghamdi
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Faisal Alhaffaf
- Division of Pediatric Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Ahmed AlAwfi
- Division of Pediatric Gastroenterology, King Saud Medical City, Riyadh, Saudi Arabia
| | - Abdulrahman AlSweed
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Manal AlShaikh
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Anjum Saeed
- Gastroenterology Division, Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Heba Assiri
- Gastroenterology Division, Department of Pediatrics, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Muhammed Salman Bashir
- Department of Biostatistics, Research Services Administration, Research Center, King Fahad Medical City, Riyadh, Saudi Arabia
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14
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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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15
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Hukkinen M, Ruuska S, Pihlajoki M, Kyrönlahti A, Pakarinen MP. Long-term outcomes of biliary atresia patients surviving with their native livers. Best Pract Res Clin Gastroenterol 2021; 56-57:101764. [PMID: 35331404 DOI: 10.1016/j.bpg.2021.101764] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/20/2021] [Accepted: 08/30/2021] [Indexed: 01/31/2023]
Abstract
Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver. The chronic cholangiopathy progresses to cirrhosis, complications of portal hypertension, recurrent cholangitis or hepatobiliary tumors necessitating LT later in life. Other common related health problems include impaired bone health, neuromotor development and quality of life. Only few high-quality trials are available for evidence-based guidance of post-PE adjuvant medical therapy or management of the disease complications. Better understanding of the pathophysiological mechanisms connecting native liver injury to clinical outcomes is critical for development of accurate follow-up tools and novel therapies designed to improve native liver function and survival.
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Affiliation(s)
- Maria Hukkinen
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Stenbackinkatu 11 PO Box 281, 00029, HUS, Finland.
| | - Satu Ruuska
- Department of Pediatric Gastroenterology, Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Stenbäckinkatu 9/PO BOX 347, 00029, HUS, Finland.
| | - Marjut Pihlajoki
- Pediatric Research Center, Children's Hospital, University of Helsinki, Tukholmankatu 8, 00290, Helsinki, Finland.
| | - Antti Kyrönlahti
- Pediatric Research Center, Children's Hospital, University of Helsinki, Stenbackinkatu 11 PO Box 281, 00029, HUS, Finland.
| | - Mikko P Pakarinen
- Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Children's Hospital, University of Helsinki, Stenbackinkatu 11 PO Box 281, 00029, HUS, Finland.
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16
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Hong KW, Igiraneza D, Davis J, Nsengiyumva A, Riner A, Petroze RT, Ntaganda E. Should We Offer Surgery for Biliary Atresia in Low-Resource Settings? Surgical Outcomes in Rwanda. J Surg Res 2020; 257:419-424. [PMID: 32892140 DOI: 10.1016/j.jss.2020.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 07/26/2020] [Accepted: 08/02/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND In many resource-limited settings, patients with biliary atresia present too late for surgical correction to be offered, and the diagnosis is fatal. As pediatric surgical and anesthesia capabilities have improved, patients in Rwanda have been offered surgical exploration. This study explores initial outcomes. METHODS Patients presenting with direct hyperbilirubinemia and clinical suspicion of biliary atresia were identified at the main university teaching hospital in Kigali, Rwanda, from January 2016 to June 2019. Patient demographics, referral history, geographic location, preoperative imaging, preoperative laboratory studies, operative details, postoperative laboratory studies, in-hospital complications, length of stay, and survival were abstracted from retrospective chart review. Descriptive analysis was performed, and univariate analysis evaluated survival and complications. RESULTS Seventeen patients were identified with biliary atresia, and thirteen were offered surgery. The median age of admission was 77 d (interquartile range [IQR] 63-92 d), with the median time wait for the operation being 19 d (IQR 9-27 d). The median age at operation was 93 d (IQR 76-123 d). In-hospital postoperative mortality was 15.4% (n = 2) and postoperative complications occurred in 46.2% (n = 6). Eleven patients survived to hospital discharge (84.6%), with a median length of stay of 8 d (IQR 6-13 d). CONCLUSIONS While future studies are needed to evaluate the long-term outcomes, this series shows that surgical treatment of biliary atresia can be safely performed in Rwanda. Early referral of direct hyperbilirubinemia is essential, particularly as limited resources and personnel may impact the time from diagnosis to operation.
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Affiliation(s)
- Kyung Woo Hong
- Division of Pediatric Surgery, Department of Surgery, University of Florida, Gainesville, Florida
| | - Deborah Igiraneza
- Division of Pediatric Surgery, University Teaching Hospital-Kigali, Kigali, Rwanda
| | - James Davis
- Division of Pediatric Surgery, Department of Surgery, University of Florida, Gainesville, Florida
| | | | - Andrea Riner
- Division of Pediatric Surgery, Department of Surgery, University of Florida, Gainesville, Florida
| | - Robin T Petroze
- Division of Pediatric Surgery, Department of Surgery, University of Florida, Gainesville, Florida.
| | - Edmond Ntaganda
- Division of Pediatric Surgery, University Teaching Hospital-Kigali, Kigali, Rwanda
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17
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Glinianaia SV, Morris JK, Best KE, Santoro M, Coi A, Armaroli A, Rankin J. Long-term survival of children born with congenital anomalies: A systematic review and meta-analysis of population-based studies. PLoS Med 2020; 17:e1003356. [PMID: 32986711 PMCID: PMC7521740 DOI: 10.1371/journal.pmed.1003356] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 08/26/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Following a reduction in global child mortality due to communicable diseases, the relative contribution of congenital anomalies to child mortality is increasing. Although infant survival of children born with congenital anomalies has improved for many anomaly types in recent decades, there is less evidence on survival beyond infancy. We aimed to systematically review, summarise, and quantify the existing population-based data on long-term survival of individuals born with specific major congenital anomalies and examine the factors associated with survival. METHODS AND FINDINGS Seven electronic databases (Medline, Embase, Scopus, PsycINFO, CINAHL, ProQuest Natural, and Biological Science Collections), reference lists, and citations of the included articles for studies published 1 January 1995 to 30 April 2020 were searched. Screening for eligibility, data extraction, and quality appraisal were performed in duplicate. We included original population-based studies that reported long-term survival (beyond 1 year of life) of children born with a major congenital anomaly with the follow-up starting from birth that were published in the English language as peer-reviewed papers. Studies on congenital heart defects (CHDs) were excluded because of a recent systematic review of population-based studies of CHD survival. Meta-analysis was performed to pool survival estimates, accounting for trends over time. Of 10,888 identified articles, 55 (n = 367,801 live births) met the inclusion criteria and were summarised narratively, 41 studies (n = 54,676) investigating eight congenital anomaly types (spina bifida [n = 7,422], encephalocele [n = 1,562], oesophageal atresia [n = 6,303], biliary atresia [n = 3,877], diaphragmatic hernia [n = 6,176], gastroschisis [n = 4,845], Down syndrome by presence of CHD [n = 22,317], and trisomy 18 [n = 2,174]) were included in the meta-analysis. These studies covered birth years from 1970 to 2015. Survival for children with spina bifida, oesophageal atresia, biliary atresia, diaphragmatic hernia, gastroschisis, and Down syndrome with an associated CHD has significantly improved over time, with the pooled odds ratios (ORs) of surviving per 10-year increase in birth year being OR = 1.34 (95% confidence interval [95% CI] 1.24-1.46), OR = 1.50 (95% CI 1.38-1.62), OR = 1.62 (95% CI 1.28-2.05), OR = 1.57 (95% CI 1.37-1.81), OR = 1.24 (95% CI 1.02-1.5), and OR = 1.99 (95% CI 1.67-2.37), respectively (p < 0.001 for all, except for gastroschisis [p = 0.029]). There was no observed improvement for children with encephalocele (OR = 0.98, 95% CI 0.95-1.01, p = 0.19) and children with biliary atresia surviving with native liver (OR = 0.96, 95% CI 0.88-1.03, p = 0.26). The presence of additional structural anomalies, low birth weight, and earlier year of birth were the most commonly reported predictors of reduced survival for any congenital anomaly type. The main limitation of the meta-analysis was the small number of studies and the small size of the cohorts, which limited the predictive capabilities of the models resulting in wide confidence intervals. CONCLUSIONS This systematic review and meta-analysis summarises estimates of long-term survival associated with major congenital anomalies. We report a significant improvement in survival of children with specific congenital anomalies over the last few decades and predict survival estimates up to 20 years of age for those born in 2020. This information is important for the planning and delivery of specialised medical, social, and education services and for counselling affected families. This trial was registered on the PROSPERO database (CRD42017074675).
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Affiliation(s)
- Svetlana V. Glinianaia
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
- * E-mail:
| | - Joan K. Morris
- Population Health Research Institute, St George’s, University of London, London, United Kingdom
| | - Kate E. Best
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Michele Santoro
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Alessio Coi
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | - Annarita Armaroli
- Center for Clinical and Epidemiological Research, University of Ferrara, Ferrara, Italy
| | - Judith Rankin
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
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18
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LeeVan E, Matsuoka L, Cao S, Groshen S, Alexopoulos S. Biliary-Enteric Drainage vs Primary Liver Transplant as Initial Treatment for Children With Biliary Atresia. JAMA Surg 2019; 154:26-32. [PMID: 30208381 DOI: 10.1001/jamasurg.2018.3180] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Importance Some infants with biliary atresia are treated with primary liver transplant (pLT), but most are initially treated with biliary-enteric drainage (BED) with a subsequent salvage liver transplant. Given the improvements in liver transplant outcomes, it is important to determine whether BED treatment remains the optimal surgical algorithm for patients with biliary atresia. Objective To compare the survival of patients with biliary atresia initially treated with BED with patients who underwent pLT. Design, Setting, and Participants This cohort study used deidentified records from the California Office of Statewide Health Planning and Development database to identify patients with biliary atresia (n = 1252) between January 1, 1990, through December 31, 2015. Patients were categorized into 1 of 2 cohorts: those who received BED treatment and those who underwent pLT. Excluded from the study were those born before January 1, 1995, and those without any documented operative intervention by age 5 years. Data analysis was performed from January 1, 1990, to December 31, 2015. Main Outcomes and Measures Overall survival was compared between the BED and pLT cohorts using the Kaplan-Meier method. The treatment's association with treatment era was examined by comparing survival before 2002 and on or after January 1, 2002. Results In total, 1252 patients with biliary atresia were identified. After exclusions, 626 remained; of these patients, 351 (56.1%) were female and 275 (43.9%) were male with a median (interquartile range) age at intervention for initial BED treatment of 65 (48-81) days. Among the 626 patients studied, initial BED treatment was performed in 313 patients (50.0%), and pLT was performed in 313 patients (50.0%). Although patients who underwent pLT had a higher mortality rate within the first 3 months after the procedure, they had a reduced risk of long-term mortality compared with patients initially managed with BED treatment (hazard ratio [HR] ≥6 months after the initial procedure, 0.19; 95% CI, 0.08-0.42; P = .01). Patients requiring salvage liver transplant had a substantially higher risk of mortality than patients who received pLT (HR, 0.43; 95% CI 0.25-0.76; P = .003). Those who underwent pLT had superior survival compared with BED treatment recipients on or after 2002 (HR, 0.16; 95% CI, 0.05-0.54; P < .001), and that persisted when censoring patients who underwent salvage liver transplant (HR, 0.23; 95% CI, 0.07-0.82; P = .01). Conclusions and Relevance Patients who underwent pLT experienced superior long-term survival compared with patients who underwent BED treatment. Multi-institutional trials are needed to determine which initial treatment is most advantageous to patients with biliary atresia.
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Affiliation(s)
- Elyse LeeVan
- Department of Surgery, Huntington Memorial Hospital, Pasadena, California
| | - Lea Matsuoka
- Division of Hepatobiliary and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Shu Cao
- Department of Preventive Medicine, Keck Hospital, University of Southern California, Los Angeles
| | - Susan Groshen
- Department of Preventive Medicine, Keck Hospital, University of Southern California, Los Angeles
| | - Sophoclis Alexopoulos
- Division of Hepatobiliary and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
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Abstract
OBJECTIVES This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available. METHODS The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed. RESULTS A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 μmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001). CONCLUSIONS In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT.
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Jain V, Burford C, Alexander EC, Sutton H, Dhawan A, Joshi D, Davenport M, Heaton N, Hadzic N, Samyn M. Prognostic markers at adolescence in patients requiring liver transplantation for biliary atresia in adulthood. J Hepatol 2019; 71:71-77. [PMID: 30876944 DOI: 10.1016/j.jhep.2019.03.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 02/14/2019] [Accepted: 03/04/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND & AIMS In patients with biliary atresia (BA), the rate of native liver survival (NLS) to adulthood has been reported as 14-44% worldwide. Complications related to portal hypertension (PHT) and cholangitis are common in adulthood. For those requiring liver transplantation (LT), the timing can be challenging. The aim of this study was to identify variables that could predict whether young people with BA would require LT when they are >16 years of age. METHODS This study was a single-centre retrospective analysis of 397 patients who underwent Kasai portoenterostomy (KP) between 1980-96 in the UK. After KP, 111/397 (28%) demonstrated NLS until 16 years of age. At final follow-up, 67 showed NLS when >16 years old (Group 1) and 22 required LT when >16 years old (Group 2). Laboratory, clinical and radiological parameters were collected for both groups at a median age of 16.06 years (13.6-17.4 years). RESULTS The need for LT when >16 years old was associated with higher total bilirubin (hazard ratio 1.03, p = 0.019) and lower creatinine (hazard ratio 0.95, p = 0.040), at 16 years, on multivariate analysis. Receiver-operating characteristic curve analysis demonstrated that a total bilirubin level of ≥21 µmol/L at 16 years old (AUROC = 0.848) predicted the need for LT when >16 years old, with 85% sensitivity and 74% specificity. Cholangitis episode(s) during adolescence were associated with a 5-fold increased risk of needing LT when >16 years old. The presence of PHT or gastro-oesophageal varices in patients <16 years old was associated with a 7-fold and 8.6-fold increase in the risk of needing LT, respectively. CONCLUSIONS BA in adulthood requires specialised management. Adult liver disease scoring models are not appropriate for this cohort. Bilirubin ≥21 µmol/L, PHT or gastro-oesophageal varices at 16 years, and cholangitis in adolescence, can predict the need for future LT in young people with BA. Low creatinine at 16 years also has potential prognostic value. LAY SUMMARY Patients with biliary atresia commonly require liver transplantation before reaching adulthood. Those who reach adulthood with their own liver are still at risk of needing a transplant. This study aimed to identify tests that could help clinicians predict which patients with biliary atresia who reach the age of 16 without a transplant will require one in later life. The study found that the presence of bilirubin ≥21 µmol/L, lower creatinine levels, and a history of portal hypertension or gastro-oesophageal varices at 16 years, as well as cholangitis in adolescence, could predict the future likelihood of needing a liver transplant for young people with biliary atresia.
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Affiliation(s)
- Vandana Jain
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK.
| | - Charlotte Burford
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Emma C Alexander
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Harry Sutton
- Faculty of Life Sciences and Medicine, Kings College London, London, UK
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
| | - Deepak Joshi
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - Mark Davenport
- Department of Paediatric Surgery, Kings College Hospital, London, UK
| | - Nigel Heaton
- Liver Transplant Surgery, Institute of Liver Studies, Kings College Hospital, London, UK
| | - Nedim Hadzic
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
| | - Marianne Samyn
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, Kings College Hospital, London, UK
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21
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Li S, Ma N, Meng X, Zhang W, Sun C, Dong C, Wang K, Wu B, Gao W. The effects of Kasai procedure on living donor liver transplantation for children with biliary atresia. J Pediatr Surg 2019; 54:1436-1439. [PMID: 30243738 DOI: 10.1016/j.jpedsurg.2018.07.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/19/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the effects of Kasai procedure (hepatic portoenterostomy) on living donor liver transplantation (LDLT) for children with biliary atresia (BA). METHODS From January 2006 to January 2014, 150 children with BA were treated with LDLT in China. The children were categorized into pre-Kasai and non-Kasai groups, based on whether they had previously undergone Kasai procedure. Clinical data were retrospectively analyzed, and the difference in postoperative survival was compared between the groups. Preoperative data, including height, weight, serum bilirubin, and pediatric end-stage liver disease score, and perioperative blood loss, operation duration, incidence of postoperative surgical complications including vascular complications, bile duct complications, lymphatic fluid leakage, and digestive tract fistula were compared between the groups. RESULTS In total, 89 and 61 children were categorized in the pre-Kasai and non-Kasai groups, respectively. The 1-, 6-, and 12-month survival was 97.8%, 95.4%, and 95.4% for the Kasai group, and 98.4%, 96.7%, and 96.7% for the non-Kasai group, respectively (P > 0.05). The differences in mean operation duration and mean blood loss, and the incidences of outflow tract obstruction, portal vein stenosis, hepatic artery thrombosis, bile duct complications, lymphatic fluid leakage, and digestive tract fistula were not statistically significant between the groups (P > 0.05). CONCLUSION Kasai procedure could effectively delay the requirement of liver transplantation. In light of previous findings that Kasai procedure could significantly improve the liver transplantation-free survival of children with BA, we suggest that Kasai procedure should be used as a first-line treatment method for this condition. TYPE OF STUDY Treatment Study. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Shanni Li
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Nan Ma
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Xingchu Meng
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Wei Zhang
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Chao Sun
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Chong Dong
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Kai Wang
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Bin Wu
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China
| | - Wei Gao
- Tianjin First Center Hospital, Key Laboratory of Organ Transplant of Tianjin, China.
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22
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Aspelund G, Mahdi EM, Rothstein DH, Wakeman DS. Transitional care for patients with surgical pediatric hepatobiliary disease: Choledochal cysts and biliary atresia. J Gastroenterol Hepatol 2019; 34:966-974. [PMID: 30552863 DOI: 10.1111/jgh.14575] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 11/13/2018] [Accepted: 12/09/2018] [Indexed: 12/14/2022]
Abstract
Choledochal cysts (CDCs) and biliary atresia (BA) are rare pediatric hepatobiliary anomalies that require surgical intervention due to increased risk of malignancy and liver failure, respectively. The underlying disease and operative procedures place patients at risk for long-term complications, which may continue to affect them into adulthood. Lack of a transitional care model in the health-care system potentiates the challenges they will face following aging out of their pediatric providers' care. We sought to elucidate the long-term complications and challenges patients with CDCs and BA face, review the current literature regarding transitioning care, and propose guidelines aiding adult providers in continued care and surveillance of these patients. A literature review was performed to assess short-term and long-term complications after surgery and the current standards for transitioning care in patients with a history of CDCs and BA. While transitional programs exist for patients with other gastrointestinal diseases, there are few that focus on CDCs or BA. Generally, authors encourage medical record transmission from pediatric to adult providers, ensuring accuracy of information and compliance with treatment plans. Patients with CDCs are at risk for developing biliary malignancies, cholangitis, and anastomotic strictures after resection. Patients with BA develop progressive liver failure, necessitating transplantation. There are no consensus guidelines regarding timing of follow up for these patients. Based on the best available evidence, we propose a schema for long-term surveillance.
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Affiliation(s)
- Gudrun Aspelund
- Department of Pediatric Surgery, Maria Fareri Children's Hospital, Valhalla, New York, USA
| | - Elaa M Mahdi
- Department of Surgery, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
| | - David H Rothstein
- Department of Pediatric Surgery, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA
| | - Derek S Wakeman
- Department of Surgery, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA
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23
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Hukkinen M, Lohi J, Heikkilä P, Kivisaari R, Jahnukainen T, Jalanko H, Pakarinen MP. Noninvasive Evaluation of Liver Fibrosis and Portal Hypertension After Successful Portoenterostomy for Biliary Atresia. Hepatol Commun 2019; 3:382-391. [PMID: 30859150 PMCID: PMC6396371 DOI: 10.1002/hep4.1306] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 11/26/2018] [Indexed: 12/19/2022] Open
Abstract
We investigated noninvasive follow‐up markers for histologic liver fibrosis and portal hypertension (PH) in patients with biliary atresia after successful portoenterostomy (PE). Among children with bilirubin <20 µmol/L after PE (n = 39), Metavir fibrosis stage was evaluated at PE and in follow‐up protocol liver biopsies (n = 83). PH was defined as endoscopically confirmed esophageal varices or thrombocytopenia associated with splenomegaly. The accuracy of liver biochemistry and stiffness in detecting liver fibrosis and PH was analyzed by the area under the receiving operating characteristic curve (AUROC) and multiple regression models. During a median native liver survival of 8.3 years (interquartile range 2.5‐10.8 years), cirrhosis (Metavir F4) had developed in 51% of patients and PH in 54% of patients. Cirrhosis was equally common in all age tertiles of 1.2‐2.1 years (n = 10/27), 3.9‐5.8 years (n = 12/28), and 9.0‐14 years (n = 12/28). In the two oldest age tertiles, histologic liver fibrosis had progressed further in patients with PH than without PH (P < 0.001). PH was accurately predicted by the aspartate aminotransferase‐to‐platelet ratio index (APRI) (cutoff, 0.70; AUROC, 0.92), bile acids (cutoff, 49 µmol/L; AUROC, 0.91), and liver stiffness (cutoff, 16.9 kPa; AUROC, 0.89; P < 0.001 each) across all age tertiles. Liver stiffness was the most accurate predictor of cirrhosis overall (AUROC, 0.82; P < 0.001), whereas bilirubin was >11 µmol/L in the youngest tertile (AUROC, 0.91; P < 0.001), bile acids was >80 µmol/L in the middle tertile (AUROC, 0.81; P = 0.009), and liver stiffness was >24 kPa in the oldest age tertile (AUROC, 0.96; P = 0.002). Conclusion: After successful PE, development of PH associates with progression of liver fibrosis and can be accurately detected by APRI and stiffness. Liver stiffness most accurately identified cirrhosis in older children, whereas biochemical markers of cholestasis closely reflected histologic cirrhosis in younger children.
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Affiliation(s)
- Maria Hukkinen
- Pediatric Liver and Gut Research Group and Section of Pediatric Surgery Children's Hospital, Helsinki University Hospital Helsinki Finland
| | - Jouko Lohi
- Department of Pathology HUSLAB, Helsinki University Hospital Helsinki Finland
| | - Päivi Heikkilä
- Department of Pathology HUSLAB, Helsinki University Hospital Helsinki Finland
| | - Reetta Kivisaari
- HUS Medical Imaging Center, Children's Hospital, Helsinki University Hospital University of Helsinki Helsinki Finland
| | - Timo Jahnukainen
- Department of Pediatric Nephrology and Transplantation Children's Hospital, Helsinki University Hospital Helsinki Finland
| | - Hannu Jalanko
- Department of Pediatric Nephrology and Transplantation Children's Hospital, Helsinki University Hospital Helsinki Finland
| | - Mikko P Pakarinen
- Pediatric Liver and Gut Research Group and Section of Pediatric Surgery Children's Hospital, Helsinki University Hospital Helsinki Finland
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24
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Ruuska SM, Lääperi MT, Hukkinen M, Jalanko H, Kolho KL, Pakarinen MP. Growth of children with biliary atresia living with native livers: impact of corticoid therapy after portoenterostomy. Eur J Pediatr 2019; 178:341-349. [PMID: 30519970 PMCID: PMC6437119 DOI: 10.1007/s00431-018-3302-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 11/05/2018] [Accepted: 11/27/2018] [Indexed: 12/24/2022]
Abstract
We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed. At birth, BA patients were shorter (median height - 0.6 (interquartile range (IQR) - 1.3 to - 0.1) SDS, n = 28, P < 0.001) than general population. Height remained stable during early childhood (median height - 0.6 (IQR - 1.4 to 0.1) SDS for girls and - 0.4 (IQR - 1.6 to 0.2) SDS for boys at 6 years of age). Patients were of normal height adjusted weight at 6 years with a median age and sex-adjusted body mass index (ISO-BMI) of 20.9 (IQR 19.3 to 25.0) for girls and 22.1 (IQR 20.7 to 25.6) for boys. Higher (≥ 50 mg/kg) cumulative post-portoenterostomy prednisolone dosage resulted in 0.18 SDS lower height per treatment week (β - 0.18, SE 0.04, P < 0.001) compared to lower dosage (< 50 mg/kg).Conclusion: BA patients grow normally during early childhood. As high postoperative corticosteroid dosage has a short-term negative effect on height, very high dosages should be avoided. What Is Known: • Growth of biliary atresia patients has mostly been shown to be within normal limits • Corticosteroids may decrease growth rate What Is New: • Biliary atresia patients surviving with their native livers are shorter than general population and their mid-parental target height at birth • A high (> 50 mg/kg) cumulative prednisolone dosage has a negative transitory impact on height gain after portoenterostomy.
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Affiliation(s)
- Satu Maria Ruuska
- Department of Gastroenterology, Children's Hospital, Helsinki University Hospital, PL 347, 00029 HUS, Helsinki, Finland. .,Pediatric Liver and Gut Research Group, Children's Hospital, Helsinki University Hospital, Helsinki, Finland.
| | - Mitja Tapani Lääperi
- 0000 0000 9950 5666grid.15485.3dPediatric Research Center, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Maria Hukkinen
- 0000 0000 9950 5666grid.15485.3dPediatric Liver and Gut Research Group, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland ,0000 0000 9950 5666grid.15485.3dSection of Pediatric Surgery, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Hannu Jalanko
- 0000 0000 9950 5666grid.15485.3dDepartment of Pediatric Nephrology and Transplantation, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Kaija-Leena Kolho
- 0000 0001 2314 6254grid.502801.eUniversity of Tampere, Tampere, Finland ,0000 0004 0628 2985grid.412330.7Tampere University Hospital, Tampere, Finland
| | - Mikko P. Pakarinen
- 0000 0000 9950 5666grid.15485.3dPediatric Liver and Gut Research Group, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland ,0000 0000 9950 5666grid.15485.3dPediatric Research Center, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland ,0000 0000 9950 5666grid.15485.3dSection of Pediatric Surgery, Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
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25
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Hukkinen M, Kerola A, Lohi J, Jahnukainen T, Heikkilä P, Pakarinen MP. Very low bilirubin after portoenterostomy improves survival of the native liver in patients with biliary atresia by deferring liver fibrogenesis. Surgery 2018; 165:843-850. [PMID: 30514566 DOI: 10.1016/j.surg.2018.10.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 10/18/2018] [Accepted: 10/23/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Progression of fibrosis and ensuing complications determine the postoperative course of patients operated on for biliary atresia. We evaluated predictors of the progression of fibrosis in the native liver after operative treatment. METHODS Among patients whose bilirubin decreased to <34 µmol/L after portoenterostomy (n = 41), predictors of follow-up cirrhosis and the progression of fibrosis were analyzed with logistic regression and survival of their native liver was evaluated with the Kaplan-Meier method. Areas under receiving operating characteristic were used to define optimal cutoffs. RESULTS After median follow-up of 5.2 years (interquartile range 1.6-10.2) after portoenterostomy, liver biopsies showed cirrhosis in 53% of patients, and the Metavir stage remained stable or decreased in 38%. The development of cirrhosis was predicted by total or conjugated bilirubin ≥170/120 µmol/L at the time of portoenterostomy (P ≤ .009); normalization of bilirubin within 1.9 months (P = .002); total or conjugated bilirubin ≥ 12.5/7.5 µmol/L (P = .002) and aspartate aminotransferase-to-platelet ratio ≥ 0.55 at 3 months postoperatively (P = .001); and total or conjugated bilirubin ≥ 7.5/2.5 µmol/L (P ≤ .001), aspartate aminotransferase-to-platelet ratio ≥ 0.63 (P = .004), and gamma glutamyl transferase ≥ 266 U/L (P = .007) at 6 months postoperatively. In multiple regression analysis, conjugated bilirubin ≥ 2.5 µmol/L at 6 months increased the risk of cirrhosis 35-fold (P = .020), and other predictors were not predictive. Total or conjugated bilirubin < 12.5/7.5 µmol/L (P ≤ .014), aspartate aminotransferase-to-platelet ratio < 0.55 at 3 months (P = .006), and total or conjugated bilirubin < 7.5/2.5 µmol/L at 6 months postoperatively (P ≤ .014) were the strongest predictors of a stable, nonprogressive fibrosis. Decreases in total or conjugated bilirubin to < 12.5/7.5 µmol/L by 3 months and to < 7.5/2.5 µmol/L by 6 months improved survival of the native liver (log-rank P ≤ .025). Age at follow-up or at portoenterostomy, anatomic type of biliary atresia, use of postoperative steroids, and episodes of cholangitis were unrelated to the progression of fibrosis or the development of cirrhosis (P = not significant). CONCLUSION Among patients whose serum bilirubin normalizes after portoenterostomy, its rapid decrease to very low levels prolongs the survival of their native liver by delaying the progression of fibrosis.
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Affiliation(s)
- Maria Hukkinen
- Pediatric Liver and Gut Research Group and Section of Pediatric Surgery, Children's Hospital, Helsinki University Hospital, Finland
| | - Anna Kerola
- Pediatric Liver and Gut Research Group and Section of Pediatric Surgery, Children's Hospital, Helsinki University Hospital, Finland
| | - Jouko Lohi
- Department of Pathology, HUSLAB, Helsinki University Hospital, Finland
| | - Timo Jahnukainen
- Department of Pediatric Nephrology and Transplantation, Children's Hospital, Helsinki University Hospital, Finland
| | - Päivi Heikkilä
- Department of Pathology, HUSLAB, Helsinki University Hospital, Finland
| | - Mikko P Pakarinen
- Pediatric Liver and Gut Research Group and Section of Pediatric Surgery, Children's Hospital, Helsinki University Hospital, Finland.
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26
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Shankar S, Rammohan A, Reddy SM, Rela M. Living donor liver transplantation and situs inversus totalis: cutting the Gordian knot. BMJ Case Rep 2018; 2018:bcr-2018-226222. [PMID: 30317204 DOI: 10.1136/bcr-2018-226222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Liver transplantation for biliary atresia splenic malformation syndrome associated with situs inversus totalis is a challenging task due to the complexity of associated malformations and the technical proficiency required to overcome them. We present the case of a 6-month-old infant who underwent liver transplantation for biliary atresia. A reduced left lateral segment liver graft from a live donor (his mother) was implanted. The postoperative period was uneventful, and the child remained well on follow-up. Thus, such rare congenital anomalies no longer prove to be a deterrent for successful liver transplantation.
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Affiliation(s)
- Sadhana Shankar
- Institute of Liver Disease & Transplantation, Gleneagles Global Health City Chennai, Chennai, Tamil Nadu, India.,Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Ashwin Rammohan
- Institute of Liver Disease & Transplantation, Gleneagles Global Health City Chennai, Chennai, Tamil Nadu, India.,Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Srinivas Mettu Reddy
- Institute of Liver Disease & Transplantation, Gleneagles Global Health City Chennai, Chennai, Tamil Nadu, India.,Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, Chennai, Tamil Nadu, India
| | - Mohamed Rela
- Institute of Liver Disease & Transplantation, Gleneagles Global Health City Chennai, Chennai, Tamil Nadu, India.,Institute of Liver Disease & Transplantation, Dr.Rela Institute & Medical Centre, Chennai, Tamil Nadu, India.,Institute of Liver Studies, Kings College Hospital, London, UK
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27
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Pakarinen MP, Johansen LS, Svensson JF, Bjørnland K, Gatzinsky V, Stenström P, Koivusalo A, Kvist N, Almström M, Emblem R, Björnsson S, Backman T, Almaas R, Jalanko H, Fischler B, Thorup J. Outcomes of biliary atresia in the Nordic countries - a multicenter study of 158 patients during 2005-2016. J Pediatr Surg 2018; 53:1509-1515. [PMID: 28947328 DOI: 10.1016/j.jpedsurg.2017.08.048] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 08/24/2017] [Accepted: 08/27/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND/PURPOSE Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. METHODS Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005-2016. RESULTS Of the 154 patients, 148 underwent portoenterostomy mostly by assigned surgical teams at median age of 64 (interquartile range 37-79) days, and 95 patients (64%) normalized their serum bilirubin concentration while living with native liver. Postoperative adjuvant medical therapy, including steroids, ursodeoxycholic acid and antibiotics was given to 137 (93%) patients. Clearance of jaundice associated with young age at surgery and favorable anatomic type of biliary atresia, whereas annual center caseload >3 patients and diagnostic protocol without routine liver biopsy predicted early performance of portoenterostomy. The cumulative 5-year native liver and overall survival estimate was 53% (95% CI 45-62) and 88% (95% CI 83-94), respectively. Portoenterostomy age <65days and annual center caseload >3 patients were predictive for long-term native liver survival, while normalization of serum bilirubin after portoenterostomy was the major predictor of both native liver and overall 5-year survival. CONCLUSIONS The outcomes of biliary atresia in the Nordic countries compared well with previous European studies. Further improvement should be pursued by active measures to reduce patient age at portoenterostomy. RETROSPECTIVE PROGNOSIS STUDY Level II.
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Affiliation(s)
- Mikko P Pakarinen
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland.
| | | | - Jan F Svensson
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Sweden
| | | | | | | | - Antti Koivusalo
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland
| | - Nina Kvist
- Department of Pediatric Surgery, Rigshospitalet, Copenhagen, Denmark
| | - Markus Almström
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Sweden
| | | | | | | | - Runar Almaas
- Department of Pediatric Research, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway
| | - Hannu Jalanko
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Finland
| | - Björn Fischler
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Sweden
| | - Jørgen Thorup
- Department of Pediatric Surgery, Rigshospitalet, Copenhagen, Denmark
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Development and Validation of Novel Diagnostic Models for Biliary Atresia in a Large Cohort of Chinese Patients. EBioMedicine 2018; 34:223-230. [PMID: 30077722 PMCID: PMC6116426 DOI: 10.1016/j.ebiom.2018.07.025] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 07/06/2018] [Accepted: 07/17/2018] [Indexed: 02/07/2023] Open
Abstract
Background & aims The overlapping features of biliary atresia (BA) and the other forms of neonatal cholestasis (NC) with different causes (non-BA) has posed challenges for the diagnosis of BA. This study aimed at developing new and better diagnostic models for BA. Methods We retrospectively analyzed data from 1728 newborn infants with neonatal obstructive jaundice (NOJ). New prediction models, including decision tree (DT), random forest (RF), and multivariate logistic regression-based nomogram for BA were created and externally validated in an independent set of 508 infant patients. Results Fiver predictors, including gender, weight, direct bilirubin (DB), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT) were significantly different between the BA and non-BA groups (P < .05), from which DT, RF, and nomogram models were developed. The area under the receiver operating characteristic (ROC) curve (AUC) value for the nomogram was 0.898, which was greater than that of a single biomarker in the prediction of BA. Performance comparison of the three diagnostic models showed that the nomogram displayed better discriminative ability (sensitivity, 85.7%; specificity, 80.3%; PPV, 0.969) at the optimal cut-off value compared with DT and RF, which had relatively similar high sensitivity and PPV (0.941 and 0.947, respectively), but low specificity in the modeling group. In sub-analysis of the discriminative capacity between the nomogram and GGT (<300 or ≥ 300), we found that the nomogram was superior to the GGT alone in the preoperative diagnosis of BA. Conclusions The nomogram has demonstrated better performance for the prediction of BA, holding promise for future clinical application.
A novel nomogram has been established for prediction of biliary atresia (BA). Its discriminatory ability is significantly improved compared with GGT alone. It holds promise for clinical application for better diagnosis of BA.
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Chen SY, Lin CC, Tsan YT, Chan WC, Wang JD, Chou YJ, Lin CH. Number of cholangitis episodes as a prognostic marker to predict timing of liver transplantation in biliary atresia patients after Kasai portoenterostomy. BMC Pediatr 2018; 18:119. [PMID: 29606115 PMCID: PMC5880092 DOI: 10.1186/s12887-018-1074-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 02/20/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostomy (KP). We examined whether the number of cholangitis episodes could be a prognostic marker for liver transplant (LT) in children with BA after Kasai portoenterostomy (KP). METHODS Data for BA patients born after 1998 and undergoing KP were obtained from National Health Insurance Research Database (NHIRD), Taiwan. Patients were followed up until the end of 2011. Incidence and the number of cholangitis episodes were recorded and compared between patients based on LT status. RESULTS Ninety-six (26.8%) of the 366 BA patients underwent LT. More patients who underwent KP at < 60 days of age survived with their native liver (P = 0.007). The mean age at first cholangitis was 0.9 years and 0.8 years in the LT and non-LT groups, respectively (P = 0.868). The cumulative incidence of cholangitis within 2 years after KP did not differ between the groups (hazard ratio 1.2; 95% CI 0.9-1.6). However, the total number of cholangitis episodes was higher in the LT group within 2 years after KP (P < 0.001). CONCLUSIONS Cholangitis occurrence was not related to LT in the first 2 years after KP in BA patients, but the number of cholangitis episodes could be a prognostic marker for future LT.
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Affiliation(s)
- Szu-Ying Chen
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, 40705, Taichung, Taiwan, Republic of China.,Wuri Lin Shin Hospital, Taichung, Taiwan
| | - Chieh-Chung Lin
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, 40705, Taichung, Taiwan, Republic of China
| | - Yu-Tse Tsan
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.,School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Wei-Cheng Chan
- Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jiaan-Der Wang
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, 40705, Taichung, Taiwan, Republic of China. .,School of Medicine, China Medical University, Taichung, Taiwan.
| | - Yi-Jung Chou
- Institute of Public Health, China Medical University, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
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Long-term Results and Quality of Life Assessment in Biliary Atresia Patients: A 35-Year Experience in a Tertiary Hospital. J Pediatr Gastroenterol Nutr 2018; 66:570-574. [PMID: 29216021 DOI: 10.1097/mpg.0000000000001854] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To review long-term transplant-free survival and quality of life (QOL) of patients with biliary atresia (BA). METHODS A retrospective study reviewing all patients with Kasai operation between January 1, 1980 and December 31, 2015 was performed to evaluate the transplant-free survival. Subgroup analysis of patients older than 20 years was carried out to assess the QOL using the Short Form-36 Health Survey and incidences of disease-related complications. Comparison between patients with native and transplanted liver was performed using two-tailed independent samples t-test (P value < 0.05, significant). RESULTS The 20-year Kaplan-Meier transplant-free survival of the 141 patients in our study was 51%. The subgroup analysis of long-term survivors revealed a trend of increased prevalence of complications like esophageal varices, portal hypertension, and recurrent admissions in the patient groups with raised serum bilirubin (SB).Thirty-one patients were successfully contacted for QOL assessment, 26 (16 with native liver and 10 with transplanted liver) responded (76.5%). BA patients who were documented to have active complications have a significantly lower vitality score (50.7 vs 57.5, P = 0.015). There was no statistically significant difference in the scores between the transplanted group and the disease-free control group. However, the native liver group achieved a lower score in both the general health section (42.9 vs 49.6, P = 0.029) and the overall physical component (49.6 vs 54.4, P = 0.037). CONCLUSIONS A significant proportion of our patients survive with their native liver for more than 20 years. These long-term survivors may suffer from complications that impair their QOL. They require continuous life-long care.
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Abstract
To determine incidence and outcome of biliary atresia (BA) between ethnic groups in New Zealand (NZ), a retrospective review was undertaken of children with BA born between 2002 and 2014. Prioritized ethnicity was used to determine ethnicity and was compared to population data. Uni- and multivariate analyses were undertaken to determine demographic and biochemical factors associated with outcome. Overall incidence was 1 in 9181 (Māori 1 in 5285; European 1 in 16,228; P < 0.0001). Overall and transplant-free survival rates at 1, 2, and 5 years were 92%, 86%, 82% and 70%, 49%, 30% respectively with Māori having improved transplant-free survival (P < 0.05) despite European children undergoing Kasai earlier (49 vs 63 days). BA is more common in NZ than Europe and North America, which is attributable to a higher incidence in Māori but overall outcome is poorer. Māori have improved transplant-free survival compared to NZ European children but the reason is unknown.
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A review of long-term outcome and quality of life of patients after Kasai operation surviving with native livers. Pediatr Surg Int 2017; 33:1283-1287. [PMID: 28940041 DOI: 10.1007/s00383-017-4158-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2017] [Indexed: 02/07/2023]
Abstract
Biliary atresia (BA) is a rare neonatal cholestatic disease which leads to progressive obliterative cholangiopathy, resulting in biliary obstruction and jaundice. The standard surgical treatment is hepatoportoenterostomy (Kasai operation). Although approximately 50% of the affected infants would require liver transplantation within the first 2 years of life, the other 50% of the patients can live for years with their native liver, despite the progression of cirrhosis and chronic liver disease. Many of these patients will be affected by long-term complications such as repeated cholangitis, portal hypertension, variceal bleeding, growth problems, biochemical abnormalities, and hepatic osteodystrophy. These morbidities impose a huge impact on the quality of life of the patients and their families. Herein, we performed a comprehensive review on the clinical status and quality of life of long-term survivors of biliary atresia with their native livers, to facilitate meticulous longitudinal follow-up of these patients, and alert caregivers the probable complications to be aware of.
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Sasaki H, Tanaka H, Nio M. Current management of long-term survivors of biliary atresia: over 40 years of experience in a single center and review of the literature. Pediatr Surg Int 2017; 33:1327-1333. [PMID: 28956136 DOI: 10.1007/s00383-017-4163-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/05/2017] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Owing to several therapeutic advancements, more patients with biliary atresia now survive into adulthood while retaining their native liver. However, the optimal strategy for long-term management of such patients remains unclear. METHODS Aiming to establish the current management strategies, we reviewed previous reports of long-term outcome of BA who underwent surgery at our institution as well as the relevant literature, focusing particularly on the treatment of late complications. RESULTS Approximately 30-40% of long-term survivors of biliary atresia who retain their native liver exhibit late sequelae such as cholangitis and portal hypertension. Early and appropriate intervention with Kasai portoenterostomy is essential for ensuring long-term survival with good quality of life. In our hospital, the current standard for Kasai portoenterostomy involves dissecting the fibrous remnants along the porta hepatis, just on the level of the liver capsule. Cholangitis is an important late complication in biliary atresia, and the possibility of mechanical obstruction of the biliary drainage route or deformity of the intrahepatic bile ducts with or without gallstones should be thoroughly evaluated in patients with intractable cholangitis. Regarding portal hypertension, appropriate interventions such as endoscopic variceal treatment and partial splenic embolization are considered to provide good quality of life when hepatic function is preserved. CONCLUSION Appropriate therapeutic management is strongly recommended in selected patients with late complications.
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Affiliation(s)
- Hideyuki Sasaki
- Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan
| | - Hiromu Tanaka
- Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan
| | - Masaki Nio
- Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan.
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Abstract
The oldest survivors from the Kasai portoenterostomy originate in Sendai, Japan and are approaching their 60th birthday. These represent the tip of an expanding cohort of adults born with this previously fatal condition. Increasingly transition to adult-biased hepatologists and physicians will be the expectation of many with this condition. However unlike their usual patients with alcohol, drugs, virally mediated liver disease these are different with different expectations of health and quality of life. Cure is not on the cards for most of these and they survive still with impaired bile flow and increased liver fibrosis and cirrhosis with the threat of cholangitis and portal hypertension still apparent. We review the reported statistics on long-term survival essentially from Japan and Western Europe (such as the UK and France) and the range of complications that may still beset this group.
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Affiliation(s)
- Arun Kelay
- Department of Paediatric Surgery, Kings College Hospital, London SE5 9RS
| | - Mark Davenport
- Department of Paediatric Surgery, Kings College Hospital, London SE5 9RS.
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Abstract
OBJECTIVES Biliary atresia (BA) occurs in 0.54 of 10.000 of overall live births in the Netherlands. BA has an unfavorable prognosis: <40% of patients are cleared of jaundice after Kasai portoenterostomy (KPE), 4-year transplant-free survival rate is 46% and the 4-year survival rate is ∼75%. Little is known on difficulties in diagnosis and the outcome of BA in preterm infants. We aimed to analyze the incidence and outcome of BA in preterm infants in the Netherlands. METHODS Retrospective study including Dutch preterm infants treated for BA. Parameters included gestational age, congenital anomalies, age at KPE, days between first symptoms, and KPE and referral interval (first hospital to KPE). Outcome parameters were clearance of jaundice (COJ) and (transplant-free) survival. Data are presented as medians (ranges). RESULTS Included 28 preterm infants (13 boys/15 girls) between March 1988 and December 2015. The incidence of BA was 1.06 of 10.000 preterm live births. Gestational age was 34.8 (27.3-36.9) weeks. Congenital anomalies were present in 11 of 28 (39%) infants. Time between first symptoms and KPE was 57 (9-138) days. Referral interval was 28 (8-86) days. Age at KPE was 70 (35-145) days. COJ was achieved in 23% of cases. Four-year transplant-free survival rate was 21%. Four-year overall survival was 61%. CONCLUSIONS BA has a higher incidence in the preterm population compared to the overall BA population. The outcome of BA in preterm infants is poor, regarding COJ and (transplant-free) survival. We speculate that timely recognition of BA-related signs and symptoms in preterm infants will improve prognosis.
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Treatment Policy and Liver Histopathology Predict Biliary Atresia Outcomes: Results after National Centralization and Protocol Biopsies. J Am Coll Surg 2017; 226:46-57.e1. [PMID: 28958913 DOI: 10.1016/j.jamcollsurg.2017.09.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 07/28/2017] [Accepted: 09/07/2017] [Indexed: 01/13/2023]
Abstract
BACKGROUND Different treatment policies can influence biliary atresia outcomes, but the pathophysiology of expanding fibrosis occurring even after successful portoenterostomy remains unclear. STUDY DESIGN Clearance of jaundice (COJ) (bilirubin <20 μmol/L), native liver survival, and overall survival rates of biliary atresia patients were analyzed before and after national centralization of management, as well as in relation to native liver histopathology of protocol biopsies. RESULTS Of the 59 patients, 35 were managed after centralization and received standardized postoperative adjuvant therapy, including corticosteroids. After centralization, age at portoenterostomy decreased from 73 days to 54 days (p = 0.014) and COJ rate increased from 42% to 80% (p = 0.005), 5-year native liver survival increased from 38% to 70% (p = 0.014), and 5-year overall survival increased from 68% to 94% (p = 0.007). High-grade portal inflammation at portoenterostomy predicted COJ (odds ratio 3.66; p = 0.011) and slower fibrosis progression (β = -0.74; p = 0.005). Native liver survival was extended in patients with high-grade portal inflammation (p = 0.002) and in patients whose bilirubin normalized within 3 months (p < 0.001). Portal inflammation and cholestasis reduced only after COJ (p < 0.001), and persisting ductal reaction, reflected by cytokeratin 7-positive proliferating bile ductules and periportal hepatocytes, correlated with follow-up fibrosis (r = 0.454 to 0.763; p < 0.001 to 0.003). Cytokeratin 7 immunopositivity of periportal hepatocytes increased after COJ (p = 0.015) and was the only predictor of follow-up liver fibrosis (β = 0.36; p = 0.002) in multiple regression. CONCLUSIONS Biliary atresia outcomes improved significantly after centralization and standardized management. Resolution of cholestasis and reduction of high-grade portal inflammation postoperatively predict slower fibrosis progression and improved native liver survival, and persisting ductal reaction parallels progressive native liver fibrosis despite COJ.
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Fn14 hepatic progenitor cells are associated with liver fibrosis in biliary atresia. Pediatr Surg Int 2017; 33:593-599. [PMID: 28180936 DOI: 10.1007/s00383-017-4068-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/18/2017] [Indexed: 12/19/2022]
Abstract
PURPOSE The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia. METHODS Liver samples from biliary atresia patients are as BA group, and the normal liver derived from hepatoblastoma infants during operation are control group. The extent of fibrosis in liver samples was blindly evaluated by two experienced pathologists depending on Ishak system. The BA liver samples were divided into mild liver fibrosis group (grade I-IV, BAa) and severe liver fibrosis group (grade V-VI, BAb) to detect Fn14 protein expression. RESULTS In mRNA level, Fn14 expression was 21.23 ± 8.3 vs. 1.00 ± 0.17, p = 0.023 < 0.05 and CD133 expression was 6.02 ± 2.16 vs. 1.14 ± 0.75, p = 0.008 < 0.01 between BA group and control group. Fn14 cells co-expressed the progenitor marker CD133 in liver, and activated in BA. Fn14 andα-SMA were co-location in fibrous area in liver. Compared to the control group, Fn14, CD133, and α-SMA protein expression were 2.10 ± 0.53 vs. 0.97 ± 0.2, p = 0.001, 2.23 ± 0.57 vs. 1.00 ± 0.03, p = 0.000, 4.96 ± 2.4 vs. 1.00 ± 0.22, p = 0.001. The Fn14 protein expression was 2.60 ± 0.35 vs. 1.86 ± 0.42, p = 0.012, between BAb and BAa group. CONCLUSION Fn14 cells, which co-express the progenitor marker CD133 in liver, are HPCs and activated in BA. Fn14 + HPCs are associated with liver fibrosis in BA.
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Joshi D, Gupta N, Samyn M, Deheragoda M, Dobbels F, Heneghan MA. The management of childhood liver diseases in adulthood. J Hepatol 2017; 66:631-644. [PMID: 27914924 DOI: 10.1016/j.jhep.2016.11.013] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 11/20/2016] [Accepted: 11/21/2016] [Indexed: 12/12/2022]
Abstract
An increasing number of patients with childhood liver disease survive into adulthood. These young adults are now entering adult services and require ongoing management. Aetiologies can be divided into liver diseases that develop in young adults which present to adult hepatologists i.e., biliary atresia and Alagille syndrome or liver diseases that occur in children/adolescents and adults i.e., autoimmune hepatitis or Wilson's disease. To successfully manage these young adults, a dynamic and responsive transition service is essential. In this review, we aim to describe the successful components of a transition service highlighting the importance of self-management support and a multi-disciplinary approach. We will also review some of the liver specific aetiologies which are unique to young adults, offering an update on pathogenesis, management and outcomes.
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Affiliation(s)
- Deepak Joshi
- Institute of Liver Studies, King's College Hospital, London, UK.
| | - Nitika Gupta
- Division of Paediatric Gastroenterology, Emory University School of Medicine, Atlanta, USA
| | - Marianne Samyn
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Fabienne Dobbels
- Academic Centre for Nursing and Midwifery, Katholieke Universiteit Leuven, Belgium
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Value of Gamma-Glutamyl Transpeptidase for Diagnosis of Biliary Atresia by Correlation With Age. J Pediatr Gastroenterol Nutr 2016; 63:370-3. [PMID: 26963938 DOI: 10.1097/mpg.0000000000001168] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES The aim of the study was to analyze the value of gamma-glutamyl transpeptidase (GGT) for distinguishing biliary atresia (BA) from non-BA for patients suspected of having neonatal obstructive jaundice by correlation with age. METHODS From January 2003 to March 2014, cholangiography and/or surgical exploration were undertaken in 1469 patients with suspicion of having neonatal obstructive jaundice. A total of 1338 patients were diagnosed with BA intraoperatively. Preoperative medical records were compared between BA and non-BA patients. RESULTS Preoperative levels of total bilirubin, direct bilirubin, and GGT were significantly higher in the BA group (P < 0.05), whereas the non-BA group had higher alkaline phosphatase levels (P = 0.0003). The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin, GGT, and alkaline phosphatase was 0.584, 0.614, 0.843, and 0.398, respectively. In all age groups (i: 31-60 days; ii: 61-90 days; iii: 91-120 days; iv: ≥121 days), BA groups had higher GGT levels (in IU/L) (i: 725.3 ± 549.9; ii: 927.0 ± 679.8; iii: 1114.3 ± 823.1; iv: 767.5 ± 666.7). The level of GGT in patients with BA younger than 30 days was 834.2 ± 475.3 IU/L. GGT levels had the highest diagnostic value (0.869) in group ii (61-90 days) and the lowest diagnosis value (0.712) in group iv (≥121 days). At a cutoff of >303 IU/L in group ii (61-90 days), GGT had 82.8% sensitivity and 81.6% specificity for the discrimination of BA. CONCLUSIONS GGT levels contribute to the diagnosis of BA before 120 days. Age must be considered if using GGT levels as a diagnostic test for BA.
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40
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Teele SA, Jacobs JP, Border WL, Chanani NK. Heterotaxy Syndrome: Proceedings From the 10th International PCICS Meeting. World J Pediatr Congenit Heart Surg 2016; 6:616-29. [PMID: 26467876 DOI: 10.1177/2150135115604470] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
A session dedicated to heterotaxy syndrome was included in the program of the Tenth International Conference of the Pediatric Cardiac Intensive Care Society in Miami, Florida in December 2014. An invited panel of experts reviewed the anatomic considerations, surgical considerations, noncardiac issues, and long-term outcomes in this challenging group of patients. The presentations, summarized in this article, reflect the current approach to this complex multiorgan syndrome and highlight future areas of clinical interest and research.
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Affiliation(s)
- Sarah A Teele
- Division of Cardiovascular Critical Care, Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jeffrey P Jacobs
- Division of Cardiac Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA Johns Hopkins All Children's Heart Institute, All Children's Hospital, Saint Petersburg and Tampa, FL, USA
| | - William L Border
- Sibley Heart Center Cardiology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA
| | - Nikhil K Chanani
- Sibley Heart Center Cardiology, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA
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Bessho K. Complications and Quality of Life in Long-Term Survivors of Biliary Atresia with Their Native Livers. J Pediatr 2015; 167:1202-6. [PMID: 26382628 DOI: 10.1016/j.jpeds.2015.08.041] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2015] [Revised: 07/23/2015] [Accepted: 08/20/2015] [Indexed: 12/12/2022]
Affiliation(s)
- Kazuhiko Bessho
- Department of Pediatrics, Graduate School of Medicine, Osaka University, Suita-shi, Osaka, Japan.
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Keyzer-Dekker CMG, Lind RC, Kuebler JF, Offerhaus GJA, Ten Kate FJW, Morsink FHM, Verkade HJ, Petersen C, Hulscher JBF. Liver fibrosis during the development of biliary atresia: Proof of principle in the murine model. J Pediatr Surg 2015; 50:1304-9. [PMID: 25783404 DOI: 10.1016/j.jpedsurg.2014.12.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 12/16/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND The murine model of biliary atresia (BA) is used for examining the pathogenesis of BA. The aim of the study was description of the morphological features and illustrating the detailed development of fibrosis using the Biliary Atresia Research Consortium (BARC) system. METHODS Neonatal mice were injected intraperitoneally with rhesus rotavirus (RRV) strain (N=17). Healthy mice were the control group (N=29). All mice were sacrificed at 7 or 14days after birth. Two pathologists examined the morphological features using the BARC system; CK19, αSMA and collagen type I were assessed by immunohistochemistry. RESULTS In RRV mice, portal fibrous expansion with focal bile duct proliferation and strong portal cellular infiltrate was found in contrast to healthy mice. In RRV mice, CK19 bile duct staining was significantly less or absent (p<0.01), with stronger portal staining of collagen type I (p=0.02). Expansion of staining for αSMA was more in RRV mice (p<0.01), but αSMA portal staining was stronger in healthy mice (p=0.02). CONCLUSIONS The morphological features observed in the murine model of BA correspond with the BA characteristics according to the BARC criteria. Fibrosis is an important feature of the model. Therefore, this murine model is useful for investigating the pathogenesis of BA.
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Affiliation(s)
- Claudia M G Keyzer-Dekker
- Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands; Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Robert Cornelis Lind
- Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands
| | - J F Kuebler
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - G J A Offerhaus
- Department of Pathology, University Medical Centre Utrecht, The Netherlands
| | - F J W Ten Kate
- Department of Pathology, University Medical Centre Utrecht, The Netherlands
| | - F H M Morsink
- Department of Pathology, University Medical Centre Utrecht, The Netherlands
| | - H J Verkade
- Department of Pediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands
| | - C Petersen
- Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany
| | - J B F Hulscher
- Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
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Zhen C, Guoliang Q, Lishuang M, Zhen Z, Chen W, Jun Z, Shuli L, Kaoping G, Chao L, Xuan Y, Long L. Design and validation of an early scoring system for predicting early outcomes of type III biliary atresia after Kasai's operation. Pediatr Surg Int 2015; 31:535-42. [PMID: 25895075 DOI: 10.1007/s00383-015-3710-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/07/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND/PURPOSE The purpose of this study was to determine reliable predictors of outcome of biliary atresia (BA) after Kasai's operation. PATIENTS AND METHODS This study included two consecutive stages of infants with biliary atresia. First stage, 200 BA cases who underwent Kasai's operation at our institution between May 2006 and May 2010 were retrospectively reviewed. In the first stage, we wanted to calculate a clinical scoring system by logistic regression. For cut-off determination, receiver operating characteristic (ROC) analysis was employed. Second stage (validation of scoring system), we used our scoring system to prospectively predict the outcomes of patients underwent a Kasai operation from inspecting the accuracy of our system. RESULTS Early cholangitis, age at operation, JC time, post-operative TB, DB, AST, ALT and surgical method entered into our scoring system. The most reliable cut-offs determined by ROC analysis were 7.71 (sensitivity: 86.0%, specificity: 98.0%). We used our scoring system to predict the prognosis of the 15 BA patients and found that 13 of 15 patients were correctly predicted at the cut-off value of 7.71. CONCLUSION Our scoring system is considered to be a reliable and useful predictor of the prognosis of biliary atresia.
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Affiliation(s)
- Chen Zhen
- Department of Pediatric Surgery, Capital Institute of Pediatrics-Peking University Teaching Hospital, Yabao Road 2#, Chaoyang, Beijing, 100021, People's Republic of China
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Abstract
To date, the etiology and pathogenic underpinning of the progression of the most prevalent serious neonatal liver disease, biliary atresia, remains elusive. This disease presents as an aggressive form of neonatal cholestasis characterized by the destruction and obliteration of the extrahepatic bile ducts within the first few weeks of life and a rapid progression of biliary fibrosis, likely due to unremitting cholestasis and retention of biliary constituents including bile acids. In ∼5% of patients, biliary atresia is associated with laterality features, suggesting a genetic underpinning to a disease that begins soon after birth. However, biliary atresia does not occur within families and twins are discordant, indicating an absence of strict mendelian inheritance. Despite this, genes related to bile duct dysmorphogenesis/ciliopathies overlapping with features of biliary atresia in both humans and nonhuman model systems have been proposed. Taken together, strict genetic etiologies leading to a common pathway of a neonatal cholangiopathy resulting in biliary atresia remain elusive. Contributions from fibrogenesis- and inflammation-based studies suggest that early engagement of these pathways contributes to disease progression, but a recent double-blind study did not suggest any benefit from early use of corticosteroids. However, there are genetic contributions to the adaptation and response to cholangiopathies and cholestasis that may be present in certain populations that likely impact upon the response to hepatoportoenterostomy and subsequent biliary tract function. Studies utilizing next generation sequencing technologies (e.g., exome analysis) are ongoing in several laboratories around the world; they are expected to provide insights into genetic contributions to biliary atresia outcomes. Altogether, combinations of exome sequencing and large population studies are expected to reveal causative and modifying genes relevant to patients with biliary atresia as a means to provide therapeutic targets and potential opportunities for genetic screening.
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Affiliation(s)
- Anya Mezina
- Emory University School of Medicine, Atlanta, Ga., USA
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Abstract
BACKGROUND Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease and liver transplantation in the United States. Early diagnosis leads to improved outcomes, but diagnosis is often delayed, leading to increased rates of transplantation and mortality. METHODS A Markov model was developed to simulate the natural history and transplant-related outcomes of patients with BA in a US cohort studied for 20 years. Data regarding proportions of individuals in different health states, including transplant and death, were obtained from published literature. Costs were derived from the literature and the Johns Hopkins database of charges using the cost-to-charge ratio. Strategy A represented the status quo and assumed no screening. Strategy B used nationwide screening with the stool color card developed by the Taiwan Health Bureau. The cost associated with both strategies was compared with the number of life-years gained, deaths, and the number of transplants for a 20-year interval. A dominant strategy was one that was associated with lower cost alongside improved outcomes, including increases in life-years gained, reductions in number of deaths, and reductions in number of transplants. One-way and probabilistic sensitivity analyses were performed. RESULTS In strategy A, the 20-year cost was $142,479,725 with 3702 life-years, 74 deaths and 158 liver transplants. For strategy B, the cost was $133,893,563 with 3731.7 life-years, 71 deaths and 147 liver transplants. There was a >97% probability that screening with the stool color card would be cost saving and associated with an increase in life-years gained. Among all parameters, only stool color card specificity was associated with the potential for screening to no longer be cost saving. CONCLUSIONS Compared with no screening, screening with the stool color card is a dominant strategy associated with lower costs and better outcomes. These findings suggest that screening with the stool color card could be an important, economically feasible strategy for improving outcomes in BA in the United States.
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Ling SC. Management of adult survivors of biliary atresia. Clin Liver Dis (Hoboken) 2014; 4:86-88. [PMID: 30992929 PMCID: PMC6448743 DOI: 10.1002/cld.428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 08/30/2014] [Accepted: 09/02/2014] [Indexed: 02/04/2023] Open
Affiliation(s)
- Simon C. Ling
- Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Department of PaediatricsThe University of TorontoTorontoOntarioCanada
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47
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Nguyen KD, Sundaram V, Ayoub WS. Atypical causes of cholestasis. World J Gastroenterol 2014; 20:9418-9426. [PMID: 25071336 PMCID: PMC4110573 DOI: 10.3748/wjg.v20.i28.9418] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Revised: 03/13/2014] [Accepted: 04/05/2014] [Indexed: 02/06/2023] Open
Abstract
Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have "silent" progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.
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48
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Schreiber RA, Masucci L, Kaczorowski J, Collet JP, Lutley P, Espinosa V, Bryan S. Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis. J Med Screen 2014; 21:126-32. [PMID: 25009198 DOI: 10.1177/0969141314542115] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. SETTING AND METHODS A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. RESULTS 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). CONCLUSIONS A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.
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Affiliation(s)
- Richard A Schreiber
- Division of Pediatric Gastroenterology, Hepatology and Nutrition Department of Pediatrics, University of British Columbia, Vancouver, Canada Child and Family Research Institute, Vancouver, Canada
| | - Lisa Masucci
- Centre for Clinical Epidemiology & Evaluation, Vancouver Coastal Health Institute, BC, Canada
| | - Janusz Kaczorowski
- Dept of Family and Emergency Medicine, Université de Montréal and CRCHUM, Canada
| | - J P Collet
- Department of Pediatrics, University of British Columbia, Vancouver, Canada Child and Family Research Institute, Vancouver, Canada
| | - Pamela Lutley
- Department of Pediatrics, University of British Columbia, Vancouver, Canada
| | | | - Stirling Bryan
- School of Population & Public Health, University of British Columbia, Vancouver, Canada Centre for Clinical Epidemiology & Evaluation, Vancouver Coastal Health Institute, BC, Canada
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Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, Mazariegos GV. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Hepatology 2014; 60:362-98. [PMID: 24782219 DOI: 10.1002/hep.27191] [Citation(s) in RCA: 142] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Accepted: 04/22/2014] [Indexed: 12/16/2022]
Affiliation(s)
- Robert H Squires
- Department of Pediatrics, University of Pittsburgh School of Medicine; Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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50
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McLin VA. Biliary atresia in adolescents and young adults. Clin Liver Dis (Hoboken) 2013; 2:197-199. [PMID: 30992861 PMCID: PMC6448656 DOI: 10.1002/cld.252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 07/28/2013] [Accepted: 08/04/2013] [Indexed: 02/04/2023] Open
Affiliation(s)
- Valérie A. McLin
- Swiss Center for Liver Disease in Children, Department of PediatricsUniversity Hospitals GenevaGenevaSwitzerland
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