ALF is a devastating disease requiring coordinated care in a specialized center for best outcome. In both prospective and retrospective studies, the cause of most cases of ALF in children is indeterminate. Liver transplantation has improved short-term outcome, but there is little knowledge regarding the functional health of spontaneous survivors or of liver transplant recipients. Moreover, for patients who have indeterminate ALF, who comprise the majority of this population, there are no biochemical markers that specifically identify those who will have spontaneous recovery and will not require liver transplantation. There are no proven therapies to promote liver regeneration. It is important to understand the outcome of ALF, not only in terms of survival but also the functional status of those who recover with or without liver transplantation  (Fig. 3). Efforts to prevent ALF, to standardize care, and to understand the biology of the disease so as to develop specific therapy will improve outcome and decrease the demand for liver transplantation. If it is determined that a proportion of patients who have indeterminate ALF have defects in fatty acid oxidation, immune dysregulation, or unrecognized acetaminophen toxicity, specific therapy might be instituted that could improve outcome and avoid the need for liver transplantation. © 2006 Elsevier Inc. All rights reserved.
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