1. Metabolic and Nutritional Support
The goal of treatment is to achieve overall metabolic and hemodynamic stability, with the reasonable, though yet unproven, idea that such therapy will greatly improve conditions for hepatic regeneration and minimize the risk of complications. In patients with acute liver failure, this type of support is provided as it is for other critically ill patients, with specific caveats. Patients with acute liver failure are at increased risk for hypoglycemia, which can be prevented by an intravenous glucose infusion. Large-volume infusions of hypotonic fluids, which may result in hyponatremia and cerebral swelling, should be avoided. Patients with acute liver failure have high energy expenditure and protein catabolism, requiring nutritional support to preserve muscle bulk and immune function. Pragmatically, in patients with encephalopathy, we administer 1.0 to 1.5 g of enteral protein per kilogram per day while frequently measuring blood ammonia levels, with a lowered protein load for short periods in patients with worsening hyperammonemia or otherwise at high risk for intracranial hypertension.

2. Prognostic Evaluation
Early identification of patients who will not survive with medical therapy alone is of great practical importance in identifying potential candidates for transplantation. Since the progression of multiorgan failure results in deterioration in many patients who are awaiting transplantation, candidates for transplantation should be identified as quickly as possible.

Various prognostic evaluation systems, most of which have features derived from analyses of historical patient cohorts that were treated without transplantation, are in use worldwide. Although the details of these systems differ, they share common features. The presence of encephalopathy is a key indicator, with further consideration given to the patient's age and the severity of liver injury, as assessed by the presence of coagulopathy or jaundice. The most well characterized evaluation system is the King's College Criteria, with meta-analyses confirming that these criteria have clinically acceptable specificity but more limited sensitivity. To address these limitations, a wide variety of alternate prognostic systems and markers have been proposed. To date, none have achieved universal acceptance, though the need for improved identification of candidates for transplantation is clear.

3. Transplantation

Although transplantation is a treatment option for some specific causes of acute liver failure, such treatment is not universally available, and less than 10% of liver transplantations are performed in patients with acute liver failure. In such patients, especially those who are at risk for intracranial hypertension, intraoperative and postoperative management is challenging, and rates of survival are consistently lower than those associated with elective liver transplantation. However, outcomes have improved over time, with registry data reporting current rates of survival after transplantation of 79% at 1 year and 72% at 5 years. Most deaths after transplantation for acute liver failure occur from infection during the first 3 postoperative months. The risk of death is higher among older recipients and among those receiving older or partial grafts or grafts from donors without an identical ABO blood group. Early impaired liver-graft function is poorly tolerated in critically ill patients and predisposes them to intracranial hypertension and sepsis.