When medicine has really succeeded brilliantly in technology, as in immunization. . . or endocrinereplacement therapy, so that the therapeutic measures can be directed straight at the underlying disease mechanism and are decisively effective, the cost is likely to be very low indeed. It is when our technologies have to be applied halfway along against the progress of disease, or must be brought in after the fact to shore up the loss of destroyed tissue, that health care becomes enormously expensive. The deeper our understanding of a disease mechanism, the greater are our chances of devising direct and decisive measures to prevent disease, or to turn it around before it is too late." Lewis Thomas (1) Inborn errors of metabolism are a recognizable cause of acute or chronic liver disease, manifesting as either fulminant liver failure, cirrhosis or HCC. Orthotopic liver transplantation (OLT) is therefore accepted therapy for liver-based metabolic disease. In a recent analysis of 5,180 liver transplants performed in the United States, 5.3% were carried out for metabolic disease (2). OLT not only replaces the damaged organ but corrects the abnormal phenotype. In this issue, Schilsky et al. (3) convincingly reaffirm this hypothesis by demonstrating that OLT is lifesaving for patients with Wilson's disease, a prototypic metabolic liver disease. However, important questions remain unanswered. When should we apply this technology? Is OLT the only option available? Multiple nontransplant options are now (or soon will be) available for the treatment of metabolic liver disease. These novel management strategies not only allow more cost-effective therapy but also provide rational stewardship for valuable donor livers, making organs available for patients who do not have other options for treatment of their liver disease.
A list of potential strategies for the management of metabolic liver disease is shown in Table . Certain of these nontransplant options are currently considered the treatment of choice for the listed disorder, others have been used only in selected individuals and some are merely conceptual or theoretical hopes for the future. A few are worthy of note. In children with inborn errors of