Does adjuvant steroid therapy post-Kasai portoenterostomy improve outcome of biliary atresia? Systematic review and meta-analysis.
Topic: Hormone Therapy

The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear.

PICO
Population: Patients with biliary atresia post-Kasai portoenterostomy
Intervention: Adjuvant steroid therapy
Comparison: No adjuvant steroid therapy
Outcomes: Improvement in outcome of biliary atresia

Included studies:
title: Evaluation of a standardized protocol in the use of steroids after Kasai operation.
abstract: Although the Kasai operation is still the treatment of choice for infants with biliary atresia, the long-term success rate, as defined by survival without transplantation, is only about 25-40%. It has been proposed that post-operative inflammatory changes affect the bile flow and eventually lead to cholangitis and liver failure. Recent case reports have suggested that the administration of steroids post-operatively can improve outcomes. Since 2004, our unit has adopted a strict protocol for the use of post-operative steroids for patients who undergo Kasai operation. The aim of this study is to access the early outcomes of these patients. A retrospective analysis was carried out for all patients who received Kasai operation between 1996 and 2006. For the treatment group, patients all received prednisolone at 4 mg/kg 1 week after operation as guided by protocol. The demographics and outcomes, including post operative bilirubin level, episodes of cholangitic attack, the need for early liver transplantation (transplant within 1 year of Kasai), and transplantation-free survival, were noted. Statistical analysis was done using Fisher's exact test and unpaired t-test when appropriate. A value of P < 0.05 was considered to be statistically significant. Kasai operation was performed in 30 patients (11 boys and 19 girls) during the study period. Thirteen patients received post-operative prednisolone according to protocol. The average age at operation and the mean preoperative bilirubin levels for the steroid and non-steroid group were not significantly different. A normal post-operative bilirubin (defined as bilirubin level less than 20 mumol/L) was achieved at 6 months in 7 (53.9%) patients who received steroid and 8 (47.0%) patients who did not (P = 0.71). A statistically significant reduction in the post-operative bilirubin level was also seen at 3 and 6 months in the steroid group. Early liver transplantation was required in 5 (38.5%) patients with steroid and 5 (29.4%) patients without it (P = 0.60). No significant difference in terms of cholangitic attack was observed. There was also no steroid-associated complication reported. We conclude that lower post-operative bilirubin level can be achieved with the routine use of prednisolone. However, there is no statistical improvement in terms of early liver transplantation and cholangitis. This may be attributed to the small sample size of our study population. Based on this pilot study, a multi-centre randomized trial is needed.
title: Postoperative high-dose steroids do not improve mid-term survival with native liver in biliary atresia.
abstract: Postoperative adjuvant steroid treatment is reported to improve jaundice-free survival in biliary atresia (BA) patients and to reduce the need for early liver transplantation. However, evidence of all retrospective studies is very limited, although high-dose corticosteroids were favored. The aim of this dosage finding study was to test the most promising corticosteroid protocol in a smaller but representative series, in order to optimize the settings of upcoming prospective and long-term multicenter studies.
title: Immunosuppression as adjuvant therapy for biliary atresia.
abstract: Despite improvements in the surgical management of biliary atresia, the long-term incidence of progressive liver failure remains high. Because chronic inflammation involving both bile ducts and liver parenchyma contributes to the pathology, the authors have hypothesized that the liver damage may be altered using immunosuppressive therapy. The aim of this study was to examine the safety and efficacy of long-term steroid therapy in patients with biliary atresia.
title: The improved outlook for biliary atresia with corticosteroid therapy.
abstract: Controversy exists regarding the efficacy of corticosteroids on bile flow after Kasai portoenterostomy in biliary atresia (BA). Fourteen patients who had BA and underwent Kasai portojejunostomy between November 1990 and March 1996 were subject of this study. Corticosteroid therapy ("blast" type) was used for inadequate bile drainage. Corticosteroid support was unnecessary in one patient with good bile drainage, and corticosteroids were aggressively used in the remaining 13 patients. Two patients who had no response to an initial blast subsequently responded and now are doing well. The remaining 11 patients responded to corticosteroids with varying degrees. Three had a limited response, and two ultimately underwent liver transplantation. There was one death caused by subdural hematoma. Three had an excellent initial response. However, one subsequently deteriorated because of intractable cholangitis, requiring liver transplantation. Ten survivors with native liver are anicteric with satisfactory growth and quality of life. Aggressive corticosteroid therapy is an important part of the management after Kasai portoenterostomy. The initial response to steroids does not necessarily reflect the final outcome.
title: Effect of corticosteroid therapy on outcomes in biliary atresia after Kasai portoenterostomy.
abstract: This study tests the hypothesis that steroid administration improves the outcome of biliary atresia (BA) by evaluating the efficacy of postoperative steroid use on surgical outcomes in infants with BA.
title: Randomized, double-blind, placebo-controlled trial of corticosteroids after Kasai portoenterostomy for biliary atresia.
abstract: The objective of this study was to evaluate adjuvant corticosteroids after Kasai portoenterostomy for biliary atresia. The study consisted of a prospective, 2-center, double-blind, randomized, placebo-controlled trial of post-Kasai portoenterostomy corticosteroids (oral prednisolone: 2 mg/kg/day from day 7 to day 21 and 1 mg/kg/day from day 22 to day 28). The data were compared with chi2 or Mann-Whitney tests, as appropriate. Seventy-one postoperative infants with type 3 biliary atresia were randomized to receive either oral prednisolone (n = 36) or a placebo (n = 37). At 1 month, the median bilirubin level was lower in the steroid group (66 versus 92 micromol/L, P = 0.06), but no difference was evident at 6 (P = 0.56) or 12 (P = 0.3) months. The proportion of infants with a normal bilirubin level (<20 micromol/L) at 6 (47% versus 49%, P = 0.89) and 12 months (50% versus 40%, P = 0.35) was not significantly different. The need for transplantation by 6 (12% versus 13%, P = 0.99) and 12 months (26% versus 35%, P = 0.47) was not significantly different. The steroid effect was more pronounced in younger infants (less than 70 days at Kasai portoenterostomy, n = 51), with a reduced bilirubin level at 1 month (64 versus 117 micromol/L, P = 0.01) and with a greater proportion with a normal bilirubin level at 12 months (54% versus 37%, P = 0.22).