The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. RESULTS: A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared

with 30% for placebo; 1-sided P = .010); transplant-free survival for the Selleckchem Silmitasertib 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo

(1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). CONCLUSIONS: Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation. Acute liver failure (ALF) is characterized by loss of liver function without pre-existing chronic liver disease. The grade of hepatic encephalophathy and the international normalized ratio (INR) have been identified as the main prognostic PLX4032 nmr indicators in this disease. The clinical course in severe ALF may be characterized by the rapid development of multiorgan failure, extended intensive care, and liver transplantation may be needed. The definition of ALF has not been clearly established. The clinical presentation of coagulopathy and encephalopathy suggests the diagnosis. However, ALF with less severe Bay 11-7085 liver injury can present with coagulopathy but without encephalopathy. The historical classification of ALF

into fulminant or hyperacute, acute and subacute liver failure depending on the duration of clinical symptoms has no prognostic relevance.1 Causes of ALF with unfavorable prognosis include Wilson’s disease, Budd-Chiari syndrome, and non-A hepatitis B or C. In the United States, approximately 2000 cases of ALF are recorded annually and cause 6% of liver-related deaths overall.2 The most common etiologies of ALF are drug-induced injury, viral hepatitis, and indeterminate causes. Acetaminophen (AAF) toxicity accounts for 39% of the cases of ALF in the United States and Europe.3 Recovery from ALF is determined by the metabolic consequences of reduced liver cell mass, the release of toxic substrates from hepatocytes, and the capability of hepatocyte regeneration.