Effects of adjuvant therapy on the outcomes of surgical management of extrahepatic biliary atresia
Authors: Carlo Pulitanò, Akihiko Kobayashi, Luca Aldrighetti
Journal: Hepatology (2008)

We read with great interest the article by Davenport et al. regarding the role of adjuvant corticosteroids therapy after Kasai portoenterostomy for biliary atresia.1 Steroids have been in use for more than 30 years as an adjunct in the management of biliary atresia. Although some comparative studies have reported beneficial effects of adjuvant steroid therapy, the value of these studies is limited by their retrospective nature.2-4 For these reasons, the putative value of adjuvant steroid administration after the Kasai procedure is still open to question. The clinical trial by Davenport et al. is actually the only randomized clinical trial of this controversial topic. Infants in the steroid group received a low dose of prednisolone (2 mg/kg/day from day 7 to day 21 followed by 1 mg/kg/day from day 22 to day 28) starting postoperatively 1 week after Kasai portoenterostomy.1 The authors concluded that steroids do not significantly increase the proportion of infants achieving a normal bilirubin level or reduce the need for liver transplantation 1 year later. However, the low-dose regimen and the delayed postoperative administration of steroids may have affected the results of this study. Controversy exists regarding the optimal steroid treatment regimen. Kobayashi et al. reported that large-dose prednisolone therapy (20 mg/day) had a positive impact on the time it took for patients with biliary atresia post-portoenterostomy to become jaundice free.5 A lower initial dose of 10 mg/day was ineffective. Meyers et al. reported accelerated clearance of jaundice and decreased need for early liver transplantation when using, ursodeoxycholic acid, intravenous antibiotics, and high-dose steroids, starting at the time of surgery.3 Similarly, Dillon et al. noted longer jaundice-free status and survival without liver transplantation using long-term high-dose steroids.4 There are several experimental and clinical evidences that an initial high pulse dose of steroids may be effective in improving liver function. Steroids may improve bile flow through the induction of Na+/H+ exchanger and Cl/HCO3 exchanger activity, which results in an increase in bicarbonate excretion.6 Increased levels of inflammatory mediators are present at the time of portoenterostomy, with a marked increase of proinflammatory cytokines, which represent a strong stimulus for the initiation of fibrosis in the liver.7 When given in high doses, steroids have pronounced anti-inflammatory and immunosuppressive effects, decreasing edema and collagen deposition, inhibiting scarring, and arresting migration of infiltrating monocytes and lymphocytes.8 It is of great interest that the possible clinical effects of a high pulse dose of steroids include the prevention of bacterial translocation and immunosuppression induced by the operation itself.9, 10 Concerns exist on the clinical use of high-dose steroids, because of the possible side effects and the risk of adrenal suppression. However, no adverse effects have actually been reported in the previous study about high-dose steroids.2-4 We believe that intraoperative high pulse doses of steroids (up to 20 mg/kg/day) with tapers lasting 2 to 3 weeks followed by a low dose of prednisone may still represent a safe and effective adjuvant therapy after Kasai portoenterostomy for biliary atresia. Future randomized trials are necessary to evaluate the possible benefits of early high-dose regimens of adjuvant corticosteroids. Carlo Pulitanò*, Akihiko Kobayashi , Luca Aldrighetti*, * Department of Surgery–Liver Unit, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy, Department of surgery, University of Tsukuba, Ibaraki, Japan.