William F. Balistreri, MD

Disclosures

December 27, 2013

In This Article

Pathophysiology of Acute Liver Failure

Acute liver failure (ALF) is a syndrome of intense systemic inflammatory response characterized by multiorgan system failure and, frequently, death if liver transplantation is not performed. In patients with ALF, platelet-derived microparticles and sub-micron-sized membrane fragments (involved in intercellular signaling and hemostasis) increase in proportion to the severity of the inflammatory response and organ failure, suggesting a possible pathogenic role.

Stravitz and colleagues[18] assessed 1598 patients in the ALF Study Group Registry and determined that the development of thrombocytopenia, a previously uncharacterized feature of the ALF syndrome, occurs simultaneously with increases in plasma microparticles. They postulate that a reduction in platelets and an increase in platelet microparticles, which parallel the severity of the systemic inflammatory response, may predict the development of multisystem organ failure and a poor outcome. They further speculate that platelet fragmentation into microparticles may mediate the systemic complications of ALF.

Therapeutic Options for Patients With Biliary Atresia

Biliary atresia, a rapidly fibrosing cholangiopathy that obstructs the extrahepatic bile duct, is the most common cause of end-stage liver disease in children and the most frequent indication for pediatric liver transplantation. The primary treatment is surgical excision of the fibrotic biliary remnant followed by Roux-en-Y hepatoportoenterostomy, which has a reported success rate for restoring bile drainage of approximately 50%. Despite treatment, the intrahepatic cholangiopathy progresses, and more than 70% of patients ultimately require liver transplantation. Therefore, there is a need for adjunct therapies to improve survival with the native liver.

On the basis of their anti-inflammatory effects, corticosteroids have been proposed and are frequently used in clinical practice in the management of biliary atresia. Bezerra and colleagues[19] conducted the Steroids in Biliary Atresia Randomized Trial (START) to determine whether adding high-dose corticosteroid therapy to surgical intervention is superior to surgical therapy alone.

Children with biliary atresia (n = 140) were enrolled from 14 US centers participating in the ChiLDREN Network, which is sponsored by the National Institute for Diabetes and Digestive and Kidney Disorders. They were randomly assigned to receive intravenous methylprednisolone/oral prednisolone (4 mg/kg/day for 2 weeks, then 2 mg/kg for 2 weeks, followed by a tapering protocol over the next 9 weeks) or placebo within 72 hours of hepatoportoenterostomy.

High-dose corticosteroid therapy did not result in significantly improved bile drainage at 6 months or greater transplant-free survival up to 2 years of age in children with biliary atresia. Bezerra and colleagues concluded that corticosteroid therapy after hepatoportoenterostomy for patients with biliary atresia cannot be recommended.

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