The Journal of Pediatrics
Volume 148, Issue 4 , Pages 432-435, April 2006

Prognosis of biliary atresia: What can be further improved?

  • Christophe Chardot, MD, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: Pr Christophe Chardot, Hôpital des Enfants, Service de chirurgie pédiatrique, Rue Willi Donzé 6, CH 1205 GENEVE, Switzerland.
    • ,
  • Marie-Odile Serinet, MD

Hôpital des Enfants, Service de chirurgie pédiatrique, Rue Willi Donzé 6, CH 1205 GENEVE, Switzerland

Article Outline

 

Biliary atresia is characterized by obliteration of intrahepatic and extrahepatic bile ducts of unknown origin, occurring in the perinatal period.1 The first descriptions of biliary atresia were published at the end of the 19th century.2 Various surgical techniques were proposed in the first half of the 20th century, attempting to restore the biliary drainage. Except in “favorable” cases, where some biliary ducts remained patent and could be anastomosed to the intestine, the results were disappointing, without significant difference in outcome with untreated patients.3

See related article, p 467

The first important surgical progress came with the Kasai operation,4, 5 which consists of a resection of all the extrahepatic bile ducts and anastomosis of a jejunal en Y loop at the porta hepatis. In Western countries, short-term clearance of jaundice can be achieved in 50% to 60% of the patients after the Kasai operation,6, 7, 8, 9 about one third of the patients can survive with native liver at the age of 10 years,10, 11, 12, 13 and one fourth at age 20 years (63 of 271 patients who underwent operation in Paris between 1968 and 1983).14 In Japan, the rate of early clearance of jaundice is 57% in the national registry15 to 75% in Sendai,16 and the 10-year survival rate with native liver is 53% to 54%.15, 16 The reasons for the discrepancy of median-term results between Japan and Western countries remain unclear. At age 20 years, reported survival rates with native liver are 14% in Tokyo (16 of 115 children who underwent operation between 1968 and 1985),17 15% in Nagoya (6 of 39 patients who underwent operation from 1969),18 and 40% in Sendai (40 of 112 patients who underwent surgery between 1969 and 1980).19 Data are still scarce for survival with native liver beyond the age of 30 years: 11% (4 patients) in the Parisian study,14 8% (6/78 patients who underwent operation between 1951 and 1968) in Sendai.19 Noteworthy, these data correlate with 11% of the patients who reach adolescence without clinical or biologic signs of chronic liver disease.20

The second significant milestone in the treatment of patients with biliary atresia was the use of liver transplantation when the Kasai operation failed to restore sufficient biliary flow or when life-threatening complications of biliary cirrhosis occur.21 Since its widening clinical application in the early 1980s,22 the results of pediatric liver transplantation for biliary atresia regularly improved over the last 20 years, exceeding 90% success today23 (Table). This progress is related to the improvement of surgical techniques and postoperative care, as well as a better medical preparation of the child to the operation, especially regarding the nutritional status.24

Table. Evolution of the prognosis of biliary atresia since 1976
SeriesRefN patients starting point (N available for follow-up)Kasai op. or technical variantsAge at Kasai op.Patients without Kasai op.SNLPatients dead without liver transplantationSpLTOS of patients with biliary atresia
Multicentric mainly North America 1976–8926904 from diagnosis (670)816(>100centers)Median 69 days44/904(4.9%)———After Kasai op. 5-year actuarial OS: 48%
National UK 1980–19829114 from diagnosis (105)107(16centers)Median 9 weeks7/114(6.1%)After Kasai op. Actual SNL at last follow-up (mean 2 years 3 months): 62/105(59.0%)——Actual OS at last follow-up (mean 2 years 3 months) 64 / 112(57.1%)
Range 4–36 weeks
National France 1986–9627472 from diagnosis (472)440(32centers)Median 61 days32/472(6.8%)After Kasai op. 5-year actuarial SNL 33.9%72/472(15.3%)5-year actuarial SpLT 70.8%5-year actuarial OS: 70.2%
Range 13–180 days
National Japan 1989–1999151381 from diagnosis (735)1181(93centers)Median between 61 and 70 days4/1381(0.3%)All patients with biliary atresia 1989–94 5-year actual SNL 59.7%——All patients with biliary atresia 1989–94 5-year actual OS 75.5%
National UK and Ireland 1993–95893 from diagnosis (93)91(15centers)Meridian 54 days2/91(2.2%)All patients with biliary atresia 5-year actuarial SNL: 30.1 %10/93(10.7%)Actual SpLT at last follow-up (median 2.4 yrs after LT) 33 / 37(89%)5-year actuarial OS 85%
Range 14–294 days
Multicentric USA 1997–200025104 from Kasai op.(104)104(9centers)Mean 61 days—After Kasai op. Actual SNL at age 2 years: 58 / 104(55.8%)4/104(3.8%)Actual (SpLT) at age 2 years 37 / 42(88%)After Kasai op. Actual OS at age 2 years 91.3%
Range 11–153 days
National France 1997–2002⁎271 from diagnosis (271)255(22centers)Median 57 days16/271(9%)After Kasai op. 4-year actuarial SNL 42.7%19/271(6.9%)4-year actuarial SpLT 88.8%4-year actuarial OS: 87.1%
Range 12–151
National England and Wales 1999–20026148 from diagnosis (148)142(3centers)Median 54 days6/148(4.5%)All patients with biliary atresia 4-year actuarial SNL: 51%7/148(4.7%)Actual SpLT at last follow-up (median age 2 years) 51/57(89%)4-year actuarial OS: 89%
Range 7–175 days

⁎unpublished data from the French Observatory of biliary atresia (study funded by the Programme Hospitalier de Recherche Clinique national 2002, grant 02 0079).SNL, survival with native liver; SpLT, survival post liver transplantation; OS, overall survival.

Consequently, the overall prognosis of biliary atresia from diagnosis improved in recent years, and nowadays reaches 90% patient survival (Table). In this issue of The Journal of Pediatrics, Shneider et al25 report the outcome of 104 patients with biliary atresia who underwent the Kasai operation between 1997 and 2000 in 9 US centers specialized in pediatric liver diseases and collaborating in the Biliary Atresia Research Consortium. At the age of 2 years, the actual survival rate with native liver was 55.8% and the patient survival rate was 91.3%.25

The overall prognosis of patients with biliary atresia depends on the successive steps of their management: diagnosis, Kasai operation, liver transplantation. The diagnosis of biliary atresia mandates that the main clinical symptoms (jaundice, white stools) are identified and that the child is immediately referred to a center able to diagnose biliary atresia. The delay in diagnosis may vary according to the accessibility of the health care system, its organization, and efficacy. In the industrialized world, the median age at Kasai operation is about 2 months and does not differ among countries (Table), although the diagnosis could be made much earlier in most cases.26 The age at Kasai operation is slightly lower in the UK (median 54 days) where efforts have been made to educate parents and health care staff to detect the early clinical signs of neonatal liver diseases (“yellow alert” campaign www.childliverdisease.org/jaundice). In the US collaborative study presented in this issue, Shneider et al25 show that the age at diagnosis and Kasai operation is significantly lower in white non-Hispanic patients, as compared with children from other ethnic backgrounds. The authors suggest that this difference may be due to an easier detection of jaundice in white babies, as well as a better access to medical care of their families. In India, high rates of delays before referral of patients with biliary atresia to appropriate centers for management have been reported, jeopardizing the chance of success of the Kasai operation.27 Screening methods, on the basis of the evaluation of stool color by comparison with a stool color card, have been shown simple and effective in detecting patients with biliary atresia and reducing the age at Kasai operation in Japan28 and Taiwan.29 These data indicate that further progress is still possible and necessary to earlier diagnose biliary atresia and refer the patient for surgery.

The prognosis of the Kasai operation depends on several factors. Some of them are characteristics of the patient and the disease and cannot be modified: existence of a biliary atresia splenic malformation syndrome,7, 25, 30, 31 anatomic pattern of the extrahepatic biliary remnant,7, 30, 32, 33, 34 histologic lesions of the biliary remnant,35, 36 degree of liver fibrosis at the time of Kasai operation.37, 38, 39, 40, 41, 42 Other prognostic factors are related to the management of patients with biliary atresia and therefore can be improved: age at Kasai operation,15, 26, 30, 32, 33 experience of the treating center in the management of patients with biliary atresia.8, 9, 30 This led the British health authorities to centralize all patients with biliary atresia in 3 dedicated centers, able to manage the child from diagnosis to liver transplantation. The results of this policy have been shown to be excellent, the results reaching for all patients nationwide the level of the highly specialized centers.6 The impact of postoperative medications (especially steroid therapy, ursodeoxycholic acid, antibioprophylaxis of cholangitis) is still debated, and not enough solid data are available for clear recommendations.

In the cases where liver transplantation is needed, lack of access to a liver graft at the appropriate time may significantly reduce the chances of survival of patients with biliary atresia.15 Contraindications of liver transplantation for biliary atresia have become rare, represented mainly by severe congenital heart defects (4/104 patients [3.8%] in the current US study).25 The mortality rate of children while waiting for a liver graft has drastically decreased in recent years, because of the implementation of innovative surgical techniques that increase that the availability of pediatric liver grafts: liver splitting and living-related donation. Among 755 patients with biliary atresia registered on the waiting list for liver transplantation in the USA between 1995 and 2003 and recorded in the Studies for Pediatric Liver Transplantation registry, 3% died before undergoing liver transplantation.24 Altogether, the mortality rate of patients with biliary atresia without liver transplantation decreased from more than 15% in the early days of liver transplantation to less than 5% (Table).

Outcome after pediatric liver transplantation has improved in the last 2 decades and currently exceeds 90% success.23 There again, the results may significantly vary according to the experience of the centers with liver transplantation.30, 43, 44 The preoperative condition of the child also has a determinant impact on postoperative outcome: poor nutritional status 24 and advanced liver failure 30, 45 reduce the chances of success of the procedure. Early planning and preparation of the child for liver transplantation as soon as failure of the Kasai operation is established is therefore necessary, with special attention to the correction of malnutrition.

Biliary atresia is a rare disease whose treatment is highly specialized and needs lifelong follow-up. Therapeutic results in the population of patients with biliary atresia of an entire country strongly depend on the organization and efficacy of the national health system. Besides the reports of excellence centers, repeated assessments of therapeutic results in all patients with biliary atresia by multicenter studies are necessary to further progress in the management of these patients: in this purpose, collaborative networks have been created, like Biliary Atresia Research Consortium in the USA, the Japanese biliary atresia registry, the European Federation for Biliary Atresia Research (federating the French Observatory of biliary atresia, the UK BA Registry, the European BA Registry). Hopefully, rationalization of care to patients with biliary atresia will provide each of them with the best chances of survival.

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We thank the pediatricians and surgeons of the 45 centers collaborating in the French observatory of biliary atresia (www.orpha.net/nestasso/OFAVB).

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PII: S0022-3476(06)00076-X

doi:10.1016/j.jpeds.2006.01.049

Refers to article:

  • A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000

    Benjamin L. Shneider, Morton B. Brown, Barbara Haber, Peter F. Whitington, Kathleen Schwarz, Robert Squires, Jorge Bezerra, Ross Shepherd, Philip Rosenthal, Jay H. Hoofnagle, Ronald J. Sokol, Biliary Atresia Research Consortium
    The Journal of Pediatrics April 2006 (Vol. 148, Issue 4, Pages 467-474.e1)

The Journal of Pediatrics
Volume 148, Issue 4 , Pages 432-435, April 2006

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