Biliary atresia

Although the prognosis of biliary atresia has been dramatically improved in the era of liver transplantation, the Kasai operation is still the first line of surgical treatment. Successful hepatic portoenterostomy depends on early diagnosis and surgery, adequate surgical technique, prevention of cholangitis, and precise postoperative management.     

Biliary atresia

Biliary atresia (BA) remains a devastating disease of infants. It is still a disease of largely unknown etiology although many hypotheses such as an aberrant early bile duct development, perinatal viral infection, aberrant immune response, and abnormalities of bile acids have all been suggested as possibly etiologically important. Although recent studies, using the techniques of molecular biology and immunohistochemistry, have improved the understanding of some of the inflammatory elements of BA, there is a lack of understanding of how many such disparate elements interact and relate. Clinically, the management in the majority of cases should consist of a primary portoenterostomy (Kasai procedure) to try and restore bile flow and alleviate jaundice. Transplantation should be reserved for those who develop chronic liver disease and its attendant complications. Recent series would suggest that over 50% of infants in large centers will be able to clear their jaundice and therefore have a reasonable expectation of long-term survival with a good quality-of-life.     

Biliary atresia: Outcome and management

Untreated, biliary atresia remains a fatal condition of the newborn. Most present within four to six weeks of conjugated jaundice and acholic stools, and, although still a challenging diagnosis to make, therein lies the opportunity of changing the course of this otherwise inexorable disease. The aim of surgery is to restore bile flow, alleviate jaundice and abbreviate the cholangiodestructive process within the liver. The Kasai portoenterostomy, introduced almost 50 years ago in Japan, aims to expose microscopic biliary ductules within the fibroinflammatory mass at the porta hepatis, and restore bile drainage into a mobilised Roux loop. About 50% of infants with BA will be able to clear their jaundice following Kasai alone, given appropriately experienced surgeons and if performed prior to the onset of overt cirrhosis. They have a reasonable expectation of long-term survival to adulthood with a good quality-of-life. The remainder may be candidates for liver transplantation (where available) although donor organ shortage and immunosuppresion-related complications remain significant problems.     

Biliary atresia: clinical aspects

Biliary atresia (BA) remains an enigmatic disease with a degree of etiologic heterogeneity. A number of variants can be defined clinically, and these include the syndromic group (typically BA splenic malformation), cystic BA, and cytomegalovirus (CMV) IgM +ve associated BA. The remainder, and still the largest group, may be termed isolated BA(.) There is a wide variation in incidence across the globe from 1 in 5000 in Taiwan to 1 in 20,000 live births in Northern Europe, although the reasons for such a disparity remain obscure. Management remains primarily surgical with an attempt to restore bile flow by resection of extrahepatic biliary remnants and a reconstruction portoenterostomy (the Kasai procedure), reserving liver transplantation for those where this fails or complications of chronic liver disease supervene. Clearance of jaundice to normal values has been achieved in 40%-55% of cases in large series from around the world, with an expectation of 5-year native liver survival of similar proportions.     

Biliary atresia.

Although biliary atresia is characterized by luminal obstruction of the extrahepatic bile ducts, the etiology and the pathophysiology of the liver are still controversial. The prognosis of biliary atresia has been improved after the introduction of Kasai's hepatic portoenterostomy, but there are still many problems to be solved in the treatment of this disease. Successful results of hepatic portoenterostomy depend on early diagnosis and operation, adequate operative technique, prevention of postoperative cholangitis, and precise postoperative management. However, we are on the verge of a new era in the therapy of biliary atresia combining portoenterostomy with liver transplantation.     

Biliary atresia: service delivery and outcomes

Biliary atresia is a complex disorder dependent on multidisciplinary management. A series of comprehensive national audits in the United Kingdom and France exposed a clear relationship between center volume and clinical outcomes. Different models were adopted in each country in an attempt to improve results. In the United Kingdom, the management of biliary atresia was centralized to three specialist units in 1999, whereas in France, a strategy of decentralized management with closer inter-unit cooperation was adopted in 1997. Both policy changes led to improved outcomes for infants with biliary atresia, but only centralization improved the overall results of Kasai portoenterostomy. Other countries have adopted alternative systems of audit based on voluntary registries, but the impact of these on clinical outcomes at a national level remains unknown. The utility of monitoring tools in assessing performance in biliary atresia, the importance of risk stratification, and the need for standardized definitions of outcome are highlighted.     

Biliary atresia: East versus west

Biliary atresia (BA) is a common cause of surgical jaundice during the neonatal period. It is currently considered as a spectrum of diseases with a common final pathology characterized by obliteration of the extrahepatic biliary tract and the absence of normally branching intrahepatic ducts. Though it is a global disease that can be found in all ethnicities there are some clear differences between BA arising in the East and the West. This is likely to be related to different genetic, environmental and cultural factors. BA is more frequently found in Far Eastern infants (both Chinese and Japanese) though the syndromic associations are much less common. Many Eastern countries have national screening programmes not seen in the West possibly due to debate over its cost effectiveness in countries where incidence is low. Kasai portoenterostomy (KPE) is considered as the primary treatment of BA but its outcome still remains unsatisfactory across the region. Given the complexity of BA, it is unlikely that strategic advances could be made by the sole effort of individual countries and we believe that collaboration between the East and West is the way forward.     

Biliary atresia: perspective on transplantation

In North America, long-term, jaundice-free survival following Kasai's operation for biliary atresia is 25%–35%; thus, the majority of patients require liver transplantation for salvage. The timing of organ replacement is crucial. Patients without bile drainage because of either surgical election or operative failure should be referred immediately. Patients with ongoing but inadequate biliary drainage should be referred at a time that coincides with a plateau of the growth curve or if cholangitis is recalcitrant. Portal hypertension itself is not an indication for transplantation irrespective of its manifestations. Ascites, however, when primarily due to hypoalbuminemia, is a solid indication for transplantation. Other tests of liver function are generally unreliable. Factors found to be unimportant or of questionable adverse impact on transplant outcome include previous operation, coexisting infection limited to the liver, nonpatent portal vein, and/or abnormal liver function tests. The only factor that was found to significantly influence outcome was patient size and age. Thus, bile drainage after Kasai portoenterostomy, by permitting growth, improves the chances for a favorable outcome. Transplant 1-year survival is from 60% to 88%. Liver replacement is not without complications, namely technical errors, infection, and rejection. Nonetheless, in a majority of cases hepatic transplantation provides the only opportunity for high-quality long-term survival. Offprint requests to: R. J. Hall     

Biliary atresia: unity in diversity

Biliary atresia (BA) is a rare disease of unknown origin and unsatisfying outcome. Single, multicenter and national evaluations of epidemiological and outcome data on BA have been periodically published over the course of decades. However, the diversity of the registered parameters and outcome measures impede comparability and cumulative analysis of these very worthwhile studies. Taking into account the fact that BA is a good example of translational research and transition of patients from pediatric surgery and hepatology to transplant surgery and hepatology in general, the interdisciplinary community should make every effort to develop a common platform upon which further activities are conducted. Extending this topic to BA-related diseases might increase the acceptance of research studies and enhance the effectiveness of any recommendations outlined therein. The use of the Internet-based communication platform and registry on http://www.bard-online.com represents the first step in this direction, and the database should be viewed as a helpful tool that guides further activities.     

Biliary atresia: the animal models

Biliary atresia (BA) is a progressive fibrosing process of the neonatal biliary tree and liver, of unknown origin, and an as-yet unexplained pathologic mechanism. The crucial point is to elucidate the origin of this rare disease to change palliative surgery to etiology-related procedures. Patient-based research can only begin at the time of the Kasai procedure and does not allow retracing of the pathology back to its origin. Basic research has focused on similar diseases in the veterinary literature and started to simulate BA in animal models. Unfortunately, even after 50 years of research, no knowledge has been gained from such models, which has led to a single clinical application. This article reviews BA in the context of the animal models available and discusses whether future studies are promising or futile.