Improving outcomes of biliary atresia: French national series 1986-2009.

BACKGROUND & AIMS: This study analyses the prognosis of biliary atresia (BA) in France since liver transplantation (LT) became widely available. METHODS: The charts of all BA patients living in France and born between 1986 and 2009 were reviewed. Patients were divided into 3 cohorts according to their years of birth: 1986-1996, 1997-2002, and 2003-2009. RESULTS: 1107 BA children were identified, 990 born in metropolitan France (incidence 1/18,400 live births). Kasai operation was performed in 1044 (94%), leading to complete clearance of jaundice (total serum bilirubin ≤ 20 µmol/L) in 38% of patients. Survival with native liver (SNL) after Kasai operation was 40%, 36%, and 30% at 5, 10, and 20 years, stable in the 3 cohorts. Median age at Kasai operation was 59 days, unchanged over time. Twenty-year SNL was 39%, 32%, 28%, and 19% after Kasai operation performed in the first, second, third months of life or thereafter (p=0.0002). 588 children underwent 692 LTs. Mortality without transplantation decreased over time: 16%, 7%, and 4% in the 3 cohorts (p<0.0001). Survival after transplantation was 83%, 82%, and 77% at 5, 10, and 20 years in the whole series. Five-year post-transplant survival was 75%, 90%, and 89% in the 3 cohorts (p<0.0001). In the whole series, overall BA patient survival was 81%, 80%, and 77% at 5, 10, and 20 years. Five-year BA patient overall survival increased over time: 72%, 88%, and 89% in the 3 cohorts (p<0.0001). CONCLUSIONS: BA patients currently have an 89% live expectancy, and a 30% chance to reach adulthood without transplantation. Early Kasai operation, without age threshold, reduces the need for liver transplantation until adulthood.

Prognostic value of portal pressure at the time of Kasai operation in patients with biliary atresia.

AIM: To examine the prognostic value of portal pressure at the time of Kasai operation in patients with biliary atresia (BA). PATIENTS AND METHODS: All 127 patients with BA, born between 1991 and 1996, who underwent a Kasai operation in Bicêtre Hospital were studied. Intraoperatively, the umbilical vein was catheterised and a portal pressure index (PPI), defined by the height of the physiologic saline column above the liver surface level, was measured. Overall patient survival, survival with native liver (SNL) and, in patients living with their native liver, survival without significant portal hypertension (SwsPHT) were calculated by Kaplan-Meier method and compared by univariate and multivariate analyses. RESULTS: Measurement of PPI was successful in 113/127 patients (89%) without complication. Median PPI was 15 cm (range, 5-35). Portal pressure index was positively correlated with age at surgery and histological severity of liver fibrosis. Ten-year overall patient survival was 78.2%; 10-year SNL was 35.7%. In patients living with their native liver, 5- and 10-year SwsPHT were 65.3% and 43.6%, respectively. Portal pressure index >15 cm, complete extrahepatic BA and polysplenia were independently associated with a worse SNL. Portal pressure index >15 cm and the absence of postoperative normalisation of bilirubin were independently associated with a worse SwsPHT. CONCLUSION: Biliary atresia patients with elevated portal pressure at the time of Kasai operation have lower chances of success of this procedure and a higher risk of developing portal hypertension, even if bilirubin levels normalise after the operation. Measurement of PPI was simple and safe and better predicted the postoperative outcome than did the histological scores of liver fibrosis.

Impact of age at Kasai operation on its results in late childhood and adolescence: a rational basis for biliary atresia screening.

BACKGROUND: Increased age at surgery has a negative impact on results of the Kasai operation for biliary atresia in infancy and early childhood. It remained unclear if an age threshold exists and if this effect persists with extended follow-up. In this study we examined the relationship between increased age at surgery and its results in adolescence. METHODS: All patients with biliary atresia who were living in France and born between 1986 and 2002 were included. Median follow-up in survivors was 7 years. RESULTS: Included in the study were 743 patients with biliary atresia, 695 of whom underwent a Kasai operation; 2-, 5-, 10-, and 15-year survival rates with native liver were 57.1%, 37.9%, 32.4%, and 28.5%, respectively. Median age at Kasai operation was 60 days and was stable over the study period. Whatever the follow-up (2, 5, 10, or 15 years), survival rates with native liver decreased when age at surgery increased (< or =30, 31-45, 46-60, 61-75, and 76-90 days). Accordingly, we estimated that if every patient with biliary atresia underwent the Kasai operation before 46 days of age, 5.7% of all liver transplantations performed annually in France in patients younger than 16 years could be spared. CONCLUSIONS: Increased age at surgery had a progressive and sustained deleterious effect on the results of the Kasai operation until adolescence. These findings indicate a rational basis for biliary atresia screening to reduce the need for liver transplantations in infancy and childhood.

Management of patients with biliary atresia in France: results of a decentralized policy 1986-2002.

This study analyzed the results of the decentralized management of biliary atresia (BA) in France, where an improved collaboration between centers has been promoted since 1997. Results were compared to those obtained in England and Wales, where BA patients have been centralized in three designated centers since 1999. According to their birth dates, BA patients were divided into two cohorts: cohort A, with patients born between 1986 and 1996, had 472 patients; and cohort B, with patients born between 1997 and 2002, had 271 patients. Survival rates were calculated according to the Kaplan-Meier method and compared by using the log rank test and the Cox model. Four-year overall BA patient survival was 73.6% (95% CI 69.5%-77.7%) and 87.1% (CI 82.6%-91.6%) in cohorts A and B, respectively (P < .001). Median age at time of the Kasai operation was 61 and 57 days in cohorts A and B, respectively (NS). Four-year survival with native liver after the Kasai operation was 40.1% and 42.7% in cohorts A and B, respectively (NS): 33.9% (cohort A) and 33.4% (cohort B) in the centers with two or fewer caseloads a year, 30.9% (cohort A) and 44.5% (cohort B) in the centers with 3-5 cases/year, 47.8% (cohort A) and 47.7% (cohort B) in the center with more than 20 caseloads a year. In cohorts A and B, 74 (15.7%) and 19 (7%) patients, respectively, died without liver transplantation (LT). Four-year survival after LT was 75.1% and 88.8% in cohorts A and B, respectively (P = .006). In conclusion, BA patients currently have the same chance of survival in France as in England and Wales. The early success rate of the Kasai operation remains inferior in the centers with limited caseloads in France, leading to a greater need for LTs in infancy and early childhood.

Anti-CD20 monoclonal antibody (Rituximab) treatment for Epstein-Barr virus-associated, B-cell lymphoproliferative disease in pediatric liver transplant recipients.

OBJECTIVES: Anti-B-cell immunotherapy has been used with success in adults with posttransplant B-cell lymphoproliferative disease (PTLD), but such treatment has rarely been reported in children. We report the outcome of anti-CD20 antibody (rituximab) therapy for Epstein-Barr virus (EBV)-associated PTLD in six pediatric liver transplant recipients. METHODS: In these six patients, PTLD was diagnosed within 2 to 4 months after transplantation. The tumors were classified as monomorphic or polymorphic B-cell infiltrate expressing CD20 antigen and EBV genome. Anti-CD20 therapy was associated with withdrawal of tacrolimus or ciclosporine therapy in all patients. Intravenous rituximab was administered at 375 mg/m2 once a week for 3 to 4 consecutive weeks. RESULTS: Rituximab treatment was associated with decreased EBV load, disappearance of abnormal serum immunoglobulin concentration, and disappearance of tumoral masses, which occurred 1 to 2.5 months after treatment onset. Despite rituximab therapy, one patient was diagnosed subsequently with a cerebral tumor. Five patients experienced acute liver graft rejection episodes within 10 days to 2.5 months after beginning treatment. In these patients, immunosuppression was reintroduced, but three children experienced fatal chronic rejection, whereas two experienced complete tumor remission. Three children are alive and in complete remission, with normal liver tests, 15 months to 3 years after PTLD onset. CONCLUSIONS: Rituximab therapy is an interesting approach for children with early EBV-associated PTLD after liver transplantation. It does not prevent cerebral localization, and rapid resumption of immunosuppression may be advisable to prevent lethal chronic liver graft rejection.