Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (Ϸ60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (Ϸ25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research. A cute liver failure (ALF) is a dramatic but rare clinical syndrome marked by the sudden loss of hepatic function in a person with no prior history of liver disease. The causes of ALF include viral hepatitis, drug-induced and toxin-induced liver disease, metabolic errors, ischemia, and miscellaneous rare causes. Currently, there are no specific therapies of proven benefit except for emergency liver transplantation. The many challenges in understanding and management of ALF led to the organization of a 2-day research workshop held on December 4-5, 2006 in Bethesda, Maryland, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) with support from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the Office of Rare Diseases of the National Institutes of Health (NIH). This manuscript summarizes the presentations at that meeting and the recommendations arising therefrom. Overview of ALF Epidemiology and Etiology in AdultsThe sudden loss of hepatic function in a person without preexisting liver disease defines ALF. 1,2 The most reliable signs of severe acute liver injury are the presence of coagulopathy (international normalized ratio [INR] Ն 1.5) and any degree of hepatic encephalopathy, the length of illness being considered anything Յ 24 weeks. Many patients evolve to coma within 1 week or less. The term "acute liver failure" is preferable to fulminant hepatic failure 1 or acute hepatic necrosis. 2 ALF is rare and represents a syndrome rather than a specific disease, having multiple causes that vary in course and outcome. 1401The rarity of ALF and its unpredictable, severe course make it a challenging entity for prospec...

This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

To determine the natural history of portopulmonary hypertension (POPH), a retrospective screening-right heart catheterization-survival analysis of patients was performed. We categorized patients by three treatment subgroups: (1) no therapy for pulmonary hypertension (PH) or liver transplantation (LT), (2) therapy for PH alone and (3) therapy for PH followed by LT. Seventyfour patients were identified between 1994 and 2007. Nineteen patients received no therapy for PH and no LT representing the natural history of POPH. Five-year survival was 14%, and 54% had died within 1 year of diagnosis. Five-year survival in 43 patients receiving therapy for PH but no LT was 45%, and 12% had died within 1 year of diagnosis. Twelve patients underwent LT and 5-year survival for the nine receiving therapy for PH was 67% versus 25% in the three who were not pretreated with prostacyclin therapy. The survival of untreated patients with POPH was poor. Subgroups of patients selected to medical treatment with or without LT had better long-term survival. Mortality did not correlate with baseline hemodynamic variables, type of liver disease or severity of hepatic dysfunction. Medical therapy for POPH should be considered in all patients with POPH, but the treatment effects and impact on those considered for LT still requires well-designed, prospective study before practice guidelines can be suggested.

The use of sirolimus-based immunosuppressive regimens leads to a higher incidence of wound-healing complications and will require new approaches to patient selection and management to decrease their incidence.

Many patients who have an otherwise acceptable living-kidney donor do not undergo transplantation because of the presence of antibodies against the donor cells resulting in a positive crossmatch. In the current study, 14 patients with a positive cytotoxic crossmatch (titer £1 : 16) against their living donor underwent a regimen including pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Eleven of 14 grafts (79%) are functioning well 30-600 days after transplantation. Two grafts were lost to accelerated vasculopathy and one was lost to death with good function. No hyperacute or cellular rejections occurred. Antibody-mediated rejection occurred in six patients [two clinical (14%) and four subclinical (29%)] and was reversible with plasmapheresis and steroids. Our results suggest that selected crossmatch-positive patients can be transplanted successfully with living-donor kidney allografts, using a protocol of pretransplant plasmapheresis, intravenous immunoglobulin, rituximab and splenectomy. Longer follow-up will be needed, but the absence of anti-donor antibody and good early outcomes are encouraging.