Acute Liver Failure

Acute liver failure (ALF) remains one of the most dramatic and highly mortal syndromes in modern medicine, with a poor outcome (death or need for emergency liver transplantation) in more than 50% of affected patients. However, prevention of specific etiologies of ALF, general improvements in intensive care medicine, and specific improvements in the management of the systemic complications of ALF, have markedly reduced mortality over the last 40 years. Specific ALF etiologies, including hepatitis A and B, appear to have decreased in developed nations along with improvements in sanitation and widespread vaccination. The management of specific complications—cerebral edema in particular—has lowered the proportion of ALF deaths due to intracranial hypertension, which was once the most dreaded systemic manifestation of ALF. A recent randomized, multicenter trial has documented the efficacy of high-volume plasma exchange in improving transplant-free and overall in-hospital survival. These and other advances have led to a speculation that ALF will be a “curable” clinical condition by the year 2024. Challenges persist, however, as acetaminophen (APAP) overdose continues to account for ~50% of cases of ALF in many developed nations. In the United Kingdom, legislation to limit access to the drug has led to a marked decrease in the incidence of ALF due to acetaminophen overdose: an important lesson for other governments to consider as they work to meet the goal of rendering ALF a “curable” condition. This review contains 6 figures, 10 tables and 53 references Key Words: acetaminophen, acute liver failure, cerebral edema, drug-induced liver injury, extracorporeal liver assist device, fulminant liver failure, hepatic encephalopathy, intracranial hypertension, liver transplantation