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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318282a913
Invited Review

International Incidence and Outcomes of Biliary Atresia

Jimenez-Rivera, Carolina*; Jolin-Dahel, Kheira S.*; Fortinsky, Kyle J.*; Gozdyra, Peter; Benchimol, Eric I.*

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Author Information

*Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada

Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Address correspondence and reprint requests to Carolina Jimenez-Rivera, MD, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada (e-mail:

Received 27 July, 2012

Accepted 11 December, 2012

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E.I.B. was supported by a Career Development Award from the Canadian Child Health Clinician Scientist Program.

The authors report no conflicts of interest.

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Objectives: International trends in incidence and outcomes of biliary atresia (BA) are controversial and a wide range of estimates have been reported worldwide. We reviewed the population-based literature to assess international variation of BA incidence and outcomes, and to assess the evidence for seasonal variation in incidence, centralization of Kasai hepatoportoenterostomy, and newborn screening.

Methods: We conducted a systematic review (registration number CRD42011001441) of observational or interventional research within MEDLINE, EMBASE, and the Cochrane Database, which reported incidence, prevalence, or outcomes of infants with BA. Population-based studies, defined by inclusion of an entire population or representative sample, were included. Outcomes included overall survival, native liver survival (NLS), and time to Kasai hepatoportoenterostomy. Single- or multicenter studies were excluded unless those centers captured all potential patients within a jurisdiction. Two independent data extractors reviewed the abstracts and articles.

Results: A total of 40 studies were included following review of 3128 references. A wide range of incidence was reported internationally. Ten-year overall survival ranged from 66.7% to 89%. NLS ranged from 20.3% to 75.8% at 1 to 3 years and 24% to 52.8% at 10 years. Earlier age at Kasai was a predictor of improved NLS. Seasonality was reported in 11 studies, and 3 reported an increased incidence during the months of August to March. The evidence for centralization of Kasai to high-volume centers is promising but does not account for all case-mix, provider, or health system factors involved in volume–outcome relations. Stool color card screening resulted in earlier Kasai and improved NLS in Taiwan.

Conclusions: Large, international studies could help fill the gaps in knowledge identified by this review.

Biliary atresia (BA) is a progressive obliterative disorder of intra- and extrahepatic bile ducts leading to hepatic fibrosis and frequently end-stage liver disease. If untreated, this disease is uniformly fatal (1). Up to two-thirds of children will undergo liver transplantation at some stage in their lives, including children who had an initial successful Kasai operation (2). The cause of BA is not well understood; however, multiple factors have been related to its pathogenesis including immunologic factors, genetic predisposition, ischemic events, infections, and other environmental factors. Previous reports of seasonal and geographical variations support the latter two hypotheses (3,4). Reports on the epidemiology of BA are variable, with ranging incidence estimates, potentially because of variations in study design, case ascertainment, and lack of population-based nature of the cohorts contributing to uncertainty.

Native liver survival (NLS) and overall survival (OS) rates are inversely correlated with age at Kasai operation (2,5). Moreover, attempts to improve outcomes by early diagnosis and referral have been carried out in Taiwan through a nationwide program by implementing an infant stool color card (6). The United Kingdom, however, adopted measures aimed to improve outcomes that included centralization of surgical procedures to designated centers where expertise and higher caseloads yielded better apparent long-term outcomes (7–9).

We conducted a systematic review of the literature to identify population-based studies, which assessed the incidence and outcomes of BA. Our aim was to highlight similarities and differences by geographic region in order to generate meaningful hypotheses that will inspire future research to investigate the etiology, environmental factors, outcomes, and health systems improvements in patients with BA. We used the available literature to assess the strength of associations of seasonality, centralization of management, and screening programs with BA incidence and outcomes.

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Protocol and Registration

The protocol for this systematic review was registered on the PROSPERO network on July 18, 2011 (registration number CRD42011001441) (10).

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Search Strategy

We conducted an electronic search of the following online bibliographic databases: Ovid MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1948–January 2012, Week 1), Ovid EMBASE (1974–2012 January 12), Wiley Cochrane Central Register of Controlled Trials (to Issue 4, 2011). Our detailed search strategy is outlined in the online-only table (, and was approved following peer review by an independent medical librarian using a previously published tool (11).

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Study Eligibility Criteria and Study Selection

Full-text articles were searched, with no restriction on language or year of publication. No language, date, or study design limits were imposed. Studies were included when the diagnosis of BA was confirmed by clinical, biochemical, radiological, surgical, and histological findings, or when they used defined health administrative data identification algorithms. Studies were only included if they reported the population-based incidence, prevalence, or outcomes of infants with BA. Outcomes of interest included OS, NLS, and time to Kasai operation. Additionally, articles were included if they discussed seasonal variation, temporal changes, or health system changes related to incidence and outcomes of BA, as long as they were population-based. In particular, we were interested in centralization of surgical Kasai procedures and implementation of screening for BA as health system changes potentially impacting outcomes. Observational cohort studies and interventional studies were included, as long as they were population-based, defined by inclusion of an entire population or a sample representative of a given jurisdiction (12), with incidence estimates providing a denominator for total population estimate of the relevant age group. As such, single- or multicenter studies were excluded unless those centers captured all potential patients within a given geographic or political jurisdiction. Also excluded were review articles, meta-analyses, and studies that based their incidence estimates on <5 cases of BA. The reference lists of review articles were searched for studies meeting inclusion criteria. Studies were not excluded based on potential for bias, methods of case ascertainment, or quality of analysis; however, these items were noted in data collection for discussion in this article.

Article abstracts were reviewed by 2 independent, blinded reviewers (C.J-R. and K.J.F.) to determine whether they met eligibility criteria. If reviewers were uncertain, the abstract was lacking or upon disagreement between the 2 reviewers, the full-text article was reviewed. The retrieved full text articles were then independently reviewed by 2 reviewers (C.J-R. and K.S.J-D.) for eligibility, and the decision to include or exclude was by consensus. Any disagreement was solved by consultation with a third reviewer (E.I.B.). Of 2081 abstracts reviewed, 145 were assessed in full-text format. There was substantial agreement between the first 2 reviewers (κ statistic 0.71 ± 0.06), with 17 articles requiring review by the third reviewer.

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Data Extraction

Two authors (C.J-R. and K.S.J-D.) independently completed a data extraction form for each eligible study. Forms were then reviewed to assure consistency of data extraction. Disagreement between the 2 extraction forms resulted in a third reviewer (E.I.B.) also completing the form to ensure data accuracy. The data items sought included: jurisdiction, dates and method of case ascertainment, incidence, prevalence, determination of temporal trends in incidence/prevalence (including statistical methods), determination of seasonal variation or periodicity of incidence, OS rates, NLS rates, OS and NLS by age at Kasai, and the effect of centralization of surgery or screening on outcomes.

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Summarization of Data

Description of the studies was summarized using proportions. Geographic maps of BA incidence (from studies reporting the latest incidence in a jurisdiction) were created using ArcGIS version 9.3 (ESRI, Redlands, CA). The Choropleth (shaded) map used here represents rate values using color intensity (darker color indicating higher rate). The value ranges shown on the map were derived using the manual breaks classification method. Rate values in local jurisdictions were shown only for the United Kingdom and the United States, whereas incidence estimates from other regions were expanded to the full country to allow for visibility on the map. Where incidence in a jurisdiction was reported by multiple studies, the latest incidence estimate was mapped.

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Search Results

A total of 3128 records were identified through searching; 2081 were retained for screening after duplicate records. Conference abstracts and conference proceedings were removed (Fig. 1). Of these, 149 articles were reviewed in full and 36 articles qualified for inclusion. An additional 4 studies were identified for inclusion from the reference lists of review articles and recent pertinent publication search, and therefore a total of 40 articles were included for this review. A complete listing of included studies is presented in Table 1. Twenty-seven of 40 included articles (67.5%) studies were retrospective, using surveys, chart review, disease registries, or large databases. Eight (20%) were based on active prospective surveillance and disease registries, and 5 (12.5%) used 2 methods of case ascertainment (retrospective and/or prospective).

Figure 1
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Incidence: Seasonality, Trends Over Time, and Geographical Distribution
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Incidence was reported in 28 of 40 included articles (70%) (2–4,8,9,13–35). International incidence per thousand live births is mapped in Figure 2. Of the 40 included studies, 11 studies (27.5%) described seasonal variations in incidence (3,4,16,17,20,24,25,27,28,31,32), 3 of which included analysis of temporal trends and/or geographical distribution (3,4,25). One study (31) reported trends over time and the association between incidence of BA and maternal ethnicity, vaccination against rotavirus infection, and gross domestic product. Of the 11 studies reporting seasonal variations, 8 (72.7%) used χ2 as statistical test to compare trends; only 2 studies found significant seasonal variations with increased incidence of BA from August to October (32) and December to March (25). Another study (28) described increased incidence in the months of November to January; however, no formal statistical analysis was performed. The remaining 7 studies did not demonstrate seasonal clustering. Five studies reported trends over time; however, only 3 analyzed trends statistically. One revealed an increased incidence over time using linear trend analysis (4), one revealed no change and used Poisson regression (3), and another revealed decreasing incidence over time using Poisson regression (31). Geographical distribution was described in 7 studies; however, only 2 reported significant differences. One study reported higher incidence in urban areas as compared with rural areas (20) and another showed higher incidence in the southeast when compared with the northwest regions of England and Wales (3).

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Outcomes by Age at Kasai Operation

There were 14 studies (35%) in which outcomes related to time to Kasai operation were reported. All studies demonstrated improved NLS when surgery was performed at an earlier age. Five studies reported outcomes on NLS at 2, 4, 5, 10, and 15 years if Kasai was performed before 45 days compared with other ages (ranges of P values from <0.0001 to 0.004) (16,18,23,36,37). Three studies reported better NLS at 2, 4, 5, 10, and 15 years when surgery was performed before 30 days of life compared with older ages (2,38,39). Schreiber et al (2) found no difference in NLS at 4 years comparing 2 eras (1985–1995 vs 1996–2002). Three studies compared NLS at 3, 4, and 5 years when surgery was performed before 60 days to other ages (4–6). Two of these reported improved outcomes compared with Kasai performed >60 days of age (P = 0.017 and P = 0.01) (4,6), and one reported improved outcomes compared with Kasai performed >90 days (5). Two studies measured outcomes based on clearance of jaundice, one at 3 months post-Kasai showing improved outcomes when Kasai was performed <60 days of life (P = 0.002) (15), and the other one at 1 year postsurgery (P = 0.095) (19).

Outcomes at 20 years postsurgery were recently described by De Vries et al (40), revealing an OS of 43%, NLS 27%, and improved outcomes when surgery was performed at 60 to 75 days compared to >75 days of age (P = 0.03). Outcomes by age at Kasai procedure are summarized in Table 2.

Table 2
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Volume–Outcome Relation

Outcomes by caseload are summarized in Table 3. Ten studies (including 1 from Canada, 2 from France, 1 from Germany, 1 from Finland, and 5 from the United Kingdom) reported outcomes based on institutional caseload (7–9,13,18,24,33,34,36,41). Caseload was considered high if a single institution treated >5 cases per year in 6 studies (7–9,13,36,41). Of these, 4 reported better OS or NLS at 2, 4, 5, and 10 years (7,8,13,41). The first study from the United Kingdom by McClement et al (9) reported significant differences in the likelihood of being jaundice-free when surgery was performed at a higher caseload center compared with lower caseload centers (P < 0.05). The study by Davenport et al (33) reported continued good outcomes after centralization was implemented in 1999 in the United Kingdom. In contrast, a Canadian study (36) failed to show differences in OS and NLS among patients operated on at a higher caseload center; however, on subgroup analysis, there was a significant benefit in 4-year NLS in children older than 60 days who were operated on at a higher caseload center (P = 0.02). Two other studies divided caseload into 3 categories: >20, 3 to 5, and <2 cases per year. One of these described significant differences in both OS (P = 0.0001) and NLS (P = 0.0001) at 5 and 10 years when caseload was higher (23). Serinet et al (18) described significant differences in OS (P < 0.0001) and NLS (P < 0.0001) at 4 years if Kasai operation was done at a center with higher caseload. A recent study from Finland reported better outcomes after centralization was implemented in 2005 with NLS at 1 and 2 years improving from 59% to 94% and 27% to 75% respectively; however, volume–outcome relation was never statistically assessed (34).

Table 3
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Four studies from Taiwan reported better outcomes when the Infant Stool Color Card screening program was implemented. Two of these compared outcomes before and after screening revealing significant increases in the proportion of patients undergoing Kasai operation before 60 days of life when population-based screening was implemented (62.5% vs 82.9%, P = 0.004 in the first, and 49.4% vs 65.7%, P = 0.02 in the second) (6,15). This resulted in increased number of jaundice-free patients at 3 months post-Kasai and higher NLS. One study reported a trend toward higher rates of jaundice-free survival in those undergoing Kasai before 60 days of age, although statistical significance was not reached (67.9% vs 45.5% in those undergoing Kasai after 60 days; P = 0.095) (19). Tseng et al (35) revealed a decline in the proportion of late referral and decreased time to Kasai; however, this did not reach statistical significance (P = 0.051).

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Overall Survival

Of the 40 included studies, 18 (45%) reported both OS and NLS; 4 (10%) reported OS only and 2 (5%) NLS only. Survival rates are plotted in Figure 3.

Figure 3
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Population-based studies reporting incidence and outcomes of BA are scarce. This systematic review revealed that the incidence of BA tends to be higher in east Asian countries and French Polynesia compared with Europe and North America. In addition, reports of incidence within the same country can vary dramatically, as in the case of studies from Taiwan (4,15,19,26,31,35). The majority of excluded studies reported single-center experiences, which cannot necessarily be extrapolated to the population of a region or country, particularly when estimates from tertiary and quaternary care centers are subject to referral bias. Moreover, there is a lack of data on the incidence of BA in developing countries, a barrier to identification of environmental and genetic factors in the pathogenesis of BA.

Reports on seasonal clustering and geographical distribution of cases have raised the possibility of environmental contributors to the pathogenesis of BA. Seasonal clustering raises the possibility of viral triggers, and previous reports discuss reovirus and rotavirus as the most likely virus associated with BA (42,43). A recent publication suggested a decrease in the incidence of BA after introduction of rotavirus vaccine in Taiwan (31); however, the present study also postulated socioeconomic status as a possible contributor. One study revealed higher incidence rates in rural areas of New York State compared with New York City. In addition, the seasonal pattern was felt to be stronger in rural areas of New York State with a peak in the months of September to November; however, no statistical analysis was performed (20). In Texas, there was a clustering of cases in 1976, 1977, and 1979, as well as higher incidence during the fall months (August through October) (32). Other studies failed to demonstrate seasonal variations of BA (3,16,17,44). Of note, studies assessing seasonal variation in incidence of BA did not account for statistical autocorrelation between diagnosis dates, nor were tests for heterogeneity described. Although advanced statistical methods have been described to assess seasonal variation in epidemiologic studies (45), their use is likely limited by the rarity of BA in most populations. The evidence for seasonal variation in BA incidence in the population-based literature is provocative but remains controversial.

Outcomes of BA treatment are most often reported by rates of NLS and OS, whereas some studies reported jaundice clearance. The Kasai hepatoportoenterostomy was introduced in 1955 as a method of treating the noncorrectable type of BA (46) and it became the standard of care thereafter. Success of the Kasai procedure is reported to vary according to patient age, center volume, and the use of coadjuvant therapy such as choleretics, antibiotics, and corticosteroids. Presence of associated malformations in the so-called embryonic or splenic malformation form of BA has been linked to worse outcomes in some (23,33,47), but not all studies (2,40,48–50).

We found general consensus that improved outcomes were associated with earlier age of performance of Kasai operation; however, the optimal age has not been established. The available population-based literature showed statistical benefit up to 60 days of age, but only one study specifically compared patients with surgery performed <30 days with those undergoing surgery at older ages (38). Although NLS was improved at 5 years in the <30 day group compared with those undergoing Kasai at 30 to 45 days, this difference did not hold to 10-year NLS. These results are encouraging, but further research is required to determine the long-term benefit of performing the Kasai operation in patients <30 days old. Reports from France (51) and the Netherlands (40) revealed that the benefit of earlier age of Kasai operation was maintained decades after surgery, resulting in better long-term outcomes.

A number of different screening methods have been used to identify infants at risk for BA and intervene earlier. The literature includes reports of measurement of urinary sulfated bile salts (52), near-infrared reflectance spectroscopy to measure conjugated bilirubin in stools (53), and measurement of conjugated bile acids in dried blood spots using tandem mass spectrometry (54). Studies have suggested that screening of newborns by measurement of serum conjugated bilirubin after birth may identify those requiring further investigation for BA (55–57); however, the only population-based studies found in the literature assessed the role of the stool color card to help parents determine whether stools were acholic. A pilot study carried out in Taiwan from 2002 to 2003 revealed a high sensitivity and specificity of an infant stool color card (89.7% and 99.9%, respectively (19)). This prompted the launch of a universal screening program in Taiwan in 2004. Hsiao et al (15) reported significantly higher rates of jaundice clearance in children undergoing Kasai before 60 days of life after the screening program was launched. This study also demonstrated an increased rate of children diagnosed before the age of 60 days after screening was implemented, findings supported by a more recent study (6). The high prevalence of BA in Taiwan would indicate a higher prescreening probability of disease and therefore a greater likelihood of effect on outcomes and cost-effectiveness. The stool color card screening method is promising but should be validated in lower prevalence populations before application to other jurisdictions.

Significant controversy exists when assessing outcomes by center volume of Kasai procedures performed. The first national UK survey conducted in 1980–1982 found improved outcomes in patients undergoing Kasai operation in centers with higher caseload volume (9). Subsequently, a second national survey from 1993 to 1995 (8) revealed improved outcomes when surgery was performed at higher caseload centers, and improved outcomes were noted after centralization to 3 UK centers (41). Davenport et al (33) described continued improved outcomes after centralization and compared them to reports from other countries where centralization was not implemented; NLS at 4/5 years was 46% in this report compared with 20% to 39% in other countries, except from Japan where 4/5 year NLS was reported at 53% and 62% in 2 different eras (21). In other countries where no centralization policy exists, retrospective studies have demonstrated improved outcomes in high caseload centers (13,23), whereas others found no significant difference (18,36). Interestingly, a Canadian study demonstrated improved outcomes only for infants older than 60 days at Kasai in higher-volume centers, with no significant effect of center volume on the full BA population (36). This implies that subgroups of patients may benefit more from surgeon or center experience; however, the majority of included studies were not powered to analyze subgroups. In France, where no centralization policy exists, NLS was initially worse in patients treated in lower-volume centers (18,23). Following a policy of increased collaboration among centers, and some lower-volume centers ceasing their provision of Kasai voluntarily, there was no longer a significant difference observed by center volume in recent years (18). Over time, there was improvement in NLS in centers performing 3 to 5 surgeries per year, but no change in NLS in high- (≥20 cases per year) or low-volume (<2 cases per year) centers. These changes imply a complex interaction among the provider education, center volume, changes in medical therapy over time, and surgeon skill in the volume–outcome relation. Although a surgical–volume relation may be present, the present literature has not deduced the minimum number of Kasai procedures required for improved outcomes or whether this outcome relation curve flattens with volumes >5 cases per year. Included studies did not determine whether other factors within the high-volume centers contribute to improved outcomes, such as case-mix, provider and hospital characteristics, individual surgeon volume, health system funding, or change in medical therapy and surgical technique over time. Future large prospective studies should incorporate these factors in multilevel regression models to determine the factors involved. Additionally, experimental studies to determine the surgical technique associated with improved outcomes of Kasai should be undertaken. These research designs would require prospective collaborative studies because no single nation has sufficient cases of BA to be sufficiently powered. International collaborative population-level studies would allow for greater statistical power and could result in stronger evidence, policy-change, and improved outcomes for children with BA.

Lastly, this systematic review revealed a wide range of OS and NLS rates in the literature. Short-term (1–3 years) NLS ranged from 20.3% to 75.8%. Long-term outcomes were similarly variable. Ten-year NLS rates ranged from 24% to 52.8% and OS ranged from 66.7% to 89%. A single recent study reported 20-year outcomes; OS was 43% and NLS was 27% (40). The lower OS reported in Japan could be explained by low transplantation rates in that country up to the early 1990s (21). Again, the available literature does not address the reasons for the high variability in outcomes seen. Case-mix, patient or provider treatment choice, health system factors, phenotype, or environmental factors may all play roles in patient outcomes.

This is the first systematic review of the epidemiology and outcomes of BA to assess population-based studies. Although our conclusions are limited by the small number of articles, which met inclusion criteria, findings are strengthened by the ability for population-level data to overcome referral bias. We also identified large gaps in research originating from developing nations. Studies were included no matter the methodology of case ascertainment or analytic techniques. Comparison across studies may have led to incorrect conclusions; however, we considered detailed evaluation of cohort design to be beyond the scope of this review. Additionally, exclusion of lower quality cohorts would have further limited our ability to detect outcomes and trends.

In summary, the incidence of BA varied among countries; however, few studies adequately analyzed trends over time or seasonality. There is unanimous agreement in the published literature on the importance of early diagnosis and surgical intervention in infants with BA. Although controversy exists with regards to the benefit of centralization of centers performing the Kasai procedure, implementation of the policy in the UK and Finland has been associated with improved outcomes. The applicability of screening strategies to international populations should be considered for early diagnosis and treatment. Further well-designed population-based studies are needed to clarify the role of infectious agents and other environmental factors in the etiology of this complex and important pediatric chronic disease.

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The authors gratefully acknowledge Margaret Sampson, MLIS, PhD, for developing the search strategy and Jessie McGowan, MLIS, PhD, for peer reviewing the MEDLINE search strategy. We also acknowledge Drs Janusz Feber and Johannes Roth for aid with article translation and Dr David Mack for review of the manuscript.

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1. Suchy FJ, Burdelski M, Tomar BS, et al. Cholestatic liver disease: Working group report of the first World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2002; 35 (suppl 2):S89–S97.

2. Schreiber RA, Barker CC, Roberts EA, et al. Biliary atresia: the Canadian experience. J Pediatr 2007; 151:659–665.e1.

3. Livesey E, Cortina BM, Sharif K, et al. Epidemiology of biliary atresia in England and Wales (1999–2006). Arch Dis Child Fetal Neonatal Ed 2009; 94:F451–F455.

4. Tiao MM, Tsai SS, Kuo HW, et al. Epidemiological features of biliary atresia in Taiwan, a national study 1996–2003. J Gastroenterol Hepatol 2008; 23:62–66.

5. de Carvalho E, dos Santos JL, da Silveira TR, et al. Biliary atresia: the Brazilian experience. J Pediatr 2010; 86:473–479.

6. Lien TH, Chang MH, Wu JF, et al. Effects of the infant stool color card screening program on 5-year outcome of biliary atresia in Taiwan. Hepatology 2011; 53:202–208.

7. McKiernan PJ, Baker AJ, Lloyd C, et al. British paediatric surveillance unit study of biliary atresia: outcome at 13 years. J Pediatr Gastroenterol Nutr 2009; 48:78–81.

8. McKiernan PJ, Baker AJ, Kelly DA. The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 2000; 355:25–29.

9. McClement JW, Howard ER, Mowat AP. Results of surgical treatment for extrahepatic biliary atresia in United Kingdom 1980–2. Survey conducted on behalf of the British Paediatric Association Gastroenterology Group and the British Association of Paediatric Surgeons. Br Med J (Clin Res Ed) 1985; 290:345–347.

10. PROSPERO. International Prospective Register of Systematic Reviews [Webpage]. National Institute for Health Research. Available at: Published July 23, 2012. Accessed January 4, 2013.

11. Sampson M, McGowan J, Cogo E, et al. An evidence-based practice guideline for the peer review of electronic search strategies. J Clin Epidemiol 2009; 62:944–952.

12. Szklo M. Population-based cohort studies. Epidemiol Rev 1998; 20:81–90.

13. Leonhardt J, Kuebler JF, Leute PJ, et al. Biliary atresia: lessons learned from the voluntary German registry. Eur J Pediatr Surg 2011; 21:82–87.

14. Grizelj R, Vukovic J, Novak M, et al. Biliary atresia: the Croatian experience 1992–1996. Eur J Pediatr 2010; 169:1529–1534.

15. Hsiao CH, Chang MH, Chen HL, et al. Universal screening for biliary atresia using an infant stool color card in Taiwan. Hepatology 2008; 47:1233–1240.

16. Wildhaber BE, Majno P, Mayr J, et al. Biliary atresia: Swiss national study, 1994–2004. J Pediatr Gastroenterol Nutr 2008; 46:299–307.

17. Wada H, Muraji T, Yokoi A, et al. Insignificant seasonal and geographical variation in incidence of biliary atresia in Japan: a regional survey of over 20 years. J Pediatr Surg 2007; 42:2090–2092.

18. Serinet MO, Broue P, Jacquemin E, et al. Management of patients with biliary atresia in France: results of a decentralized policy 1986–2002. Hepatology 2006; 44:75–84.

19. Chen SM, Chang MH, Du JC, et al. Screening for biliary atresia by infant stool color card in Taiwan. Pediatrics 2006; 117:1147–1154.

20. Caton AR, Druschel CM, McNutt LA. The epidemiology of extrahepatic biliary atresia in New York State, 1983–98. Paediatr Perinat Epidemiol 2004; 18:97–105.

21. Nio M, Ohi R, Miyano T, et al. Five- and 10-year survival rates after surgery for biliary atresia: a report from the Japanese Biliary Atresia Registry. J Pediatr Surg 2003; 38:997–1000.

22. Fischler B, Haglund B, Hjern A. A population-based study on the incidence and possible pre- and perinatal etiologic risk factors of biliary atresia. J Pediatr 2002; 141:217–222.

23. Chardot C, Carton M, Spire-Bendelac N, et al. Prognosis of biliary atresia in the era of liver transplantation: French national study from 1986 to 1996. Hepatology 1999; 30:606–611.

24. Chardot C, Carton M, Spire-Bendelac N, et al. Epidemiology of biliary atresia in France: a national study 1986–96. J Hepatol 1999; 31:1006–1013.

25. Yoon PW, Bresee JS, Olney RS, et al. Epidemiology of biliary atresia: a population-based study. Pediatrics 1997; 99:376–382.

26. Vic P, Gestas P, Mallet EC, et al. [Biliary atresia in French Polynesia. Retrospective study of 10 years]. Arch Pediatr 1994; 1:646–651.

27. Houwen RH, Kerremans II, van Steensel-Moll HA, et al. Time-space distribution of extrahepatic biliary atresia in The Netherlands and West Germany. Z Kinderchir 1988; 43:68–71.

28. Tunte W. [Incidence of congenital biliary atresia]. Z Kinderheilkd 1968; 102:275–288.

29. Perisic VN, Savcic-Kos R, Kokai GK, et al. Epidemiological and clinical study of the aetiology of cholestatic syndrome in infancy in Serbia. Arch Gastroenterohepatol 1994; 13:1–5.

30. Henriksen NT, Drablos PA, Aagenaes O. Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis. Arch Dis Child 1981; 56:622–627.

31. Lin YC, Chang MH, Liao SF, et al. Decreasing rate of biliary atresia in Taiwan: a survey, 2004–2009. Pediatrics 2011; 128:e530–e536.

32. Strickland AD, Shannon K. Studies in the etiology of extrahepatic biliary atresia: time-space clustering. J Pediatr 1982; 100:749–753.

33. Davenport M, Ong E, Sharif K, et al. Biliary atresia in England and Wales: results of centralization and new benchmark. J Pediatr Surg 2011; 46:1689–1694.

34. Lampela H, Ritvanen A, Kosola S, et al. National centralization of biliary atresia care to an assigned multidisciplinary team provides high-quality outcomes. Scand J Gastroenterol 2012; 47:99–107.

35. Tseng JJ, Lai MS, Lin MC, et al. Stool color card screening for biliary atresia. Pediatrics 2011; 128:e1209–e1215.

36. Schreiber RA, Barker CC, Roberts EA, et al. Biliary atresia in Canada: the effect of centre caseload experience on outcome. J Pediatr Gastroenterol Nutr 2010; 51:61–65.

37. Chardot C, Carton M, Spire-Bendelac N, et al. Is the Kasai operation still indicated in children older than 3 months diagnosed with biliary atresia? J Pediatr 2001; 138:224–228.

38. Serinet MO, Wildhaber BE, Broue P, et al. Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening. Pediatrics 2009; 123:1280–1286.

39. Karrer FM, Lilly JR, Stewart BA, et al. Biliary atresia registry, 1976 to 1989. J Pediatr Surg 1990; 25:1076–1080.

40. de Vries W, Homan-Van der Veen J, Hulscher JBF, et al. Twenty-year transplant-free survival rate among patients with biliary atresia. Clin Gastroenterol Hepatol 2011; 9:1086–1091.

41. Davenport M, de Ville de GJ, Stringer MD, et al. Seamless management of biliary atresia in England and Wales (1999–2002). Lancet 2004; 363:1354–1357.

42. Glaser JH, Balistreri WF, Morecki R. Role of reovirus type 3 in persistent infantile cholestasis. J Pediatr 1984; 105:912–915.

43. Morecki R, Glaser JH, Cho S, et al. Biliary atresia and reovirus type 3 infection. N Engl J Med 1982; 307:481–484.

44. Ayas MF, Hillemeier AC, Olson AD. Lack of evidence for seasonal variation in extrahepatic biliary atresia during infancy. J Clin Gastroenterol 1996; 22:292–294.

45. Stolwijk AM, Straatman H, Zielhuis GA. Studying seasonality by using sine and cosine functions in regression analysis. J Epidemiol Community Health 1999; 53:235–238.

46. Ohi R. A history of the Kasai operation: hepatic portoenterostomy for biliary atresia. World J Surg 1988; 12:871–874.

47. Shneider BL, Brown MB, Haber B, et al. A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr 2006; 148:467–474.

48. Davenport M, Tizzard SA, Underhill J, et al. The biliary atresia splenic malformation syndrome: a 28-year single-center retrospective study. J Pediatr 2006; 149:393–400.

49. Vazquez J, Lopez Gutierrez JC, Gamez M, et al. Biliary atresia and the polysplenia syndrome: its impact on final outcome. J Pediatr Surg 1995; 30:485–487.

50. Guttman OR, Roberts EA, Schreiber RA, et al. Biliary atresia with associated structural malformations in Canadian infants. Liver Int 2011; 31:1485–1493.

51. Lykavieris P, Chardot C, Sokhn M, et al. Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. Hepatology 2005; 41:366–371.

52. Matsui A, Kasano Y, Yamauchi Y, et al. Direct enzymatic assay of urinary sulfated bile acids to replace serum bilirubin testing for selective screening of neonatal cholestasis. J Pediatr 1996; 129:306–308.

53. Akiyama T, Yamauchi Y. Use of near infrared reflectance spectroscopy in the screening for biliary atresia. J Pediatr Surg 1994; 29:645–647.

54. Mushtaq I, Logan S, Morris M, et al. Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry. BMJ 1999; 319:471–477.

55. Ibrahim M, Miyano T, Ohi R, et al. Japanese Biliary Atresia Registry, 1989 to 1994. Tohoku J Exp Med 1997; 181:85–95.

56. Davis AR, Rosenthal P, Escobar GJ, et al. Interpreting conjugated bilirubin levels in newborns. J Pediatr 2011; 158:562–565.

57. Harpavat S, Finegold MJ, Karpen SJ. Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth. Pediatrics 2011; 128:e1428–e1433.

Cited By:

This article has been cited 1 time(s).

Journal of Hepatology
Is biliary atresia an immune mediated disease?
Alvarez, F
Journal of Hepatology, 59(4): 648-650.

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biliary atresia; epidemiology; liver transplantation; outcomes; pediatrics; screening

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