Pediatric Surgery and Pediatric Graduate School, Children’s Hospital Institute of Clinical Medicine, University of Helsinki and National Graduate School of Clinical Investigation Helsinki, Finland
BILIARY ATRESIA Treatment Results and Native Liver Function
HANNA LAMPELA
ACADEMIC DISSERTATION To be publicly discussed, with the permission of the Faculty of Medicine, University of Helsinki, in the Niilo Hallman Auditorium, Children’s Hospital, on 1st of March 2013, at 12 noon. Helsinki 2013
Supervisor Docent Mikko Pakarinen Pediatric Surgery Pediatric Transplantation Surgery Children’s Hospital University of Helsinki Finland Reviewers Docent Tarja Ruuska Pediatrics Tampere University Hospital Tampere, Finland Docent Paulina Salminen Gastrointestinal Surgery Turku University Hospital Turku, Finland Opponent Professor Mark Davenport Paediatric Surgery King’s College Hospital London, UK
ISBN 978-952-10-8592-5 (paperback) ISBN 978-952-10-8593-2 (PDF) http://ethesis.helsinki.fi Unigrafia Oy Helsinki 2013
“And if I have the gift of prophecy, and know all mysteries and all knowledge; and if I have all faith, so as to remove mountains, but have not love, I am nothing.” 1. Corinthians 13:2
CONTENTS ABSTRACT
6
LIST OF ORIGINAL PUBLICATIONS
8
ABBREVIATIONS
9
INTRODUCTION
10
REVIEW OF THE LITERATURE
11
History
11
Early descriptions
11
Development of operative techniques
11
Classifications
13
Epidemiology
14
Incidence
14
Seasonality
14
Etiology
14
Isolated BA
14
Congenital BA
15
Diagnosis
16
Symptoms and screening
16
Diagnostic tools and differential diagnostics
17
Treatment Kasai portoenterostomy Adjuvant medical therapy
20 20 23
Corticosteroids
23
Choleretics
23
Nutritional therapy
24
Complications
24
Portal hypertension and esophageal varices
24
Cholangitis
26
Other complications
26
Carcinoma
27
Liver transplantation
28
Outcomes
29
Factors associated with portoenterostomy success
29
Native liver and overall survival
29
Health and quality of life among adult native liver survivors
30
AIMS OF THE STUDY
31
PATIENTS AND METHODS
32
Patients and study design
32
Follow-up data collection
33
Histology and immunohistology
33
Liver function test and scores
34
Ethics
35
Statistics
35
BA treatment protocol
36
RESULTS Epidemiology Seasonality and geographic distribution Outcomes
37 37 38 39
Portoenterostomy success and native liver survival
40
Liver transplantations for BA
42
Deaths and overall survival
43
Liver function and general health among native liver survivors
44
Esophageal varices
44
Liver histology
46
Follow-up tools
48
DISCUSSION
50
CONCLUSIONS
55
ACKNOWLEDGEMENTS
56
REFERENCES
59
ABSTRACT Background. Biliary atresia (BA) is a devastating disease of infancy where the bile ducts are occluded and destroyed by a fibroinflammatory process. BA is rare but still the most common indication for childhood liver transplantation (LT). BA treatment is started with a portoenterostomy (PE) operation, adjuvant medical therapy, and nutritional treatment and continued with LT if the PE fails. Aims. The aim of this study was to investigate the incidence of BA in Finland and to evaluate the outcomes of Finnish BA patients in the era of liver transplantation, with special emphasis on the effects of treatment centralization in 2005. Furthermore, the occurrence and predictors for esophageal varices and associated gastrointestinal bleeding were assessed, the relations between liver histology and clinical outcome variables evaluated, and noninvasive follow-up tools identified. Patients and methods. BA patients born in Finland between 1987 and 2010 were identified from the national Register of Congenital Malformations and Children’s Hospital BA database. All hospital records were reviewed for diagnosis confirmation associated structural abnormalities, treatment, follow-up data, upper gastrointestinal endoscopies, gastrointestinal bleeding episodes, LT, and outcome. Liver biopsies taken at PE and LT were reviewed together with follow-up biopsies taken at a median 4.2 years after successful PE. Results. BA was diagnosed in 74 children. The incidence of BA was 1:19 900 live births. Anomalies associated with laterality disorders (heart defects, intestinal rotation disorders, poly- or asplenia, pancreatic anomalies, vascular anomalies, situs inversus) were observed in 17 (23%) patients and ten of these (14% of the cohort) met the criteria for BA splenic malformation. Births with BA were more common in autumn-winter than in spring-summer (p=0.013). Before centralization, 52 BA patients were treated in five centres with a median of zero (0-3) patients/year and after 2005, 22 patients were treated in one centre with a median of four (2-5) patients per year, p
