Early and correct diagnosis of biliary atresia is an essential element for favorable outcome of further therapeutic procedures. EHBA-related cholestasis in newborns has to be differentiated from multiple diseases associated with jaundice. Several methods of screening and staged diagnostic procedures are in discussion. Rapid development of technical equipment offers new aspects for minimal invasive diagnosis. Surgical and post-surgical therapy are not standardized and, unfortunately, most of the series of patients in each institution are too small for reliable evaluation. Cooperative strategies in diagnosis and therapy at multiple centers would be more effective to resolve these problems.
BILIARY ATRESIA: CURRENT CONCEPTS AND RESEARCH DIRECTIONS
William F. Balistreri, M.D.
Children's Hospital Medical Center, Cincinnati, Ohio
Biliary atresia is the end result of a destructive, inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract with the development of biliary cirrhosis. It is the commonest cause of chronic cholestasis in infants and children, and therefore is the most frequent indication for liver transplantation in this age group. The disease occurs worldwide, affecting an estimated 1 in 8,000 to 12,000 live births. At present, there is no specific therapy for biliary atresia; however, sequential surgical therapy begins with creation of a hepatoportoenterostomy; in those with end-stage liver disease, liver transplantation is indicated. Since most candidates are young children of small size, there is a shortage of size-matched donors for liver transplantation. At present, an increased awareness to ensure early diagnosis and development of methods to prevent progressive fibrosis are needed. These considerations are dependent on detailed studies of the pathogenesis of biliary atresia. Recent studies have focused on normal and altered bile duct morphogenesis and the role of various factors (infectious or toxic agents and metabolic insults) in isolation or in combination with a genetic or immunologic susceptibility in the etiology of biliary atresia.
BILIARY ATRESIA: FROM 95% MORTALITY TO 94% SURVIVAL.
A. Baker, A. Dhawan, N. Hadzic, M. Davenport, P. Muiesan, M. Rela, N. Heaton,
G. Mieli-Vergani, E.R.Howard
Departments of Child Health, Paediatric Surgery and Liver Transplantation,
King's College Hospital, Denmark Hill, London, SE5 9RS, UK
Twenty years ago biliary atresia (BA) was untreatable with a two year mortality of 95%. Kasai portoenterostomy (PE) and liver transplantation (OLT) have radically improved outcome but their relative roles have been debated. At our centre (KCH) a multidisciplinary team including Paediatricians, Paediatric and Transplant Surgeons provides the complete range of treatment for hepato-biliary disorders. The aim of the study was to document the results of this comprehensive approach to BA.
Between 2.12.1992 and 25.1.1995, 50 infants referred to KCH for neonatal cholestasis were found to have BA. PE was performed in all at median age 54 (range 14-120) days. A successful operation was defined as serum bilirubin less than 30 mmol/l. At median 56 (range 47-73) months, one was lost to follow up at 17 months, 8 have normal liver function tests (LFT) including aspartate, amino-transferase and gamma glutamyl transpeptidase and no clinical or ultrasound evidence of portal hypertension (pHT), 8 have abnormal LFT with only ultrasound evidence of splenomegaly, 9 have clinical evidence of PHT, 5 have significant PHT of whom 3 have impaired nutrition by arm anthropometry, 2 have serum bilirubin >30 mmol/l, 3 are listed for OLT, 14 have undergone OLT successfully, all except 1 with normal LFT. One child died after OLT and 2 while listed. Thus with expert surgery PE has 62% 5yr successful survival rate and actuarial 5 year survival including with OLT is; 94%. These results indicate that an integrated service leading to low PE failure rate with reduced need for OLT, less competition for organs and excellent OLT outcome is the optimum management of BA.
EARLY PREDICTORS OF SUCCESS OF KASAI OPERATION IN CHILDREN WITH BILIARY ATRESIA
A.Ch. Straakholder, R. Kardorff, H.Mildenberger*, J.H.H. Ehrich, B. Rodeck
Dept. of Pediatrics, *Dept. of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany
Purpose: The aim of the study was to evaluate predictive parameters of transplantation (Tx)-free or Tx-listed-free survival after Kasai procedure in children suffering from biliary atresia.
Patients and methods: 67 infants were treated with Kasai procedure at a median age of 51 days (range 19-180) after birth in our institution between 1977 and 1998. A logistic regression with subsequent roc analysis and a cox regression model was applied to all children with a minimum observation time of one year and complete data set. The response variable was Tx-free or TX-listed-free survival after observation time, as covariates 5 variables were entered i. e. ALT (parameter of liver cell damage), cholinesterase-activity and Quick's test (parameters of liver synthesis capacity), bilirubin and gGT (parameters of cholestasis) at different time points after Kasai operation.
Results: In the logistic regression analysis bilirubin concentration six weeks after Kasai procedure was identified as significant predictor of Tx-free or TX-listed-free survival in 22 patients with complete data ( log rank 8.3, p< 0.01). The subsequent roc analysis showed a cut off of 80 mmol/L with a positive predictive value of 0.76 and a negative predictive value of 0.83. The cox regression model confirmed bilirubin (3 months after Kasai) in 28 children as predictor of success of initial surgical treatment (log rank 7.9, p< 0.01).
Conclusions: Development of early bilirubin concentration after Kasai procedure reflecting reconstitution of bile flow is an important factor of predicting the prognosis of the condition. Patients with bilirubin levels above 80 mmol/L 6 weeks after surgery should be carefully looked after and early be evaluated regarding the necessity of liver transplantation in order to optimise pretransplant management.
