What is the definition of fulminant (acute) liver failure?

From the Guidelines

Fulminant liver failure is a rare and severe condition characterized by the rapid deterioration of liver function in a person without pre-existing liver disease, resulting in coagulopathy and encephalopathy within 8 weeks of symptom onset, as defined by the American Association for the Study of Liver Diseases (AASLD) 1.

Key Characteristics

• The condition is marked by the development of hepatic encephalopathy and profound coagulopathy within a short timeframe, typically 8 weeks or less 1.
• It is often defined by a prothrombin time (PT) greater than 20 seconds, an international normalized ratio (INR) greater than 1.5, although these values can vary depending on the underlying cause and the patient's overall condition 1.
• The diagnosis of fulminant liver failure can be challenging, and the condition may be precipitated by various factors, including acetaminophen overdose, typically exceeding 10 grams per day, or other hepatotoxic medications such as isoniazid 1.

Causes and Treatment

• The management of acute liver failure involves supportive care and, in some cases, liver transplantation, with the goal of preventing further liver damage and managing complications such as cerebral edema and multiorgan failure 1.
• Treatment may involve administration of N-acetylcysteine at a dose of 150 mg/kg over 1 hour, followed by 12.5 mg/kg/hour for 4 days, although the effectiveness of this treatment can vary depending on the underlying cause of liver failure 1.

Prognosis

• The prognosis for patients with fulminant liver failure is generally poor, with a high mortality rate if left untreated, although liver transplantation can significantly improve survival rates 1.
• The prognosis depends on various factors, including the underlying cause of liver failure, the patient's age, and the degree of encephalopathy, with acetaminophen overdose having a relatively better prognosis due to the availability of effective treatment 1.

From the Research

Definition of Fulminant (Acute) Liver Failure

Fulminant liver failure, also known as acute liver failure (ALF), is a clinical syndrome characterized by:

• Rapid loss of hepatocyte function
• Coagulopathy
• Encephalopathy in a patient without preexisting liver disease or cirrhosis 2, 3, 4, 5, 6 Key features of ALF include:
• Cerebral edema, which may produce uncal herniation, yielding brain stem compression and death 2
• A prolonged prothrombin time (ie, an international normalized ratio of prothrombin time of ≥1.5) and any degree of mental status alteration (HE) 4
• High morbidity and mortality, with careful attention required for hemodynamics, metabolic parameters, and infection surveillance 5

Causes and Management

The cause of ALF varies across the world, with common causes including:

• Drug toxicity
• Hepatotropic and non-hepatotropic viruses
• Herbal and dietary supplements
• Antituberculosis drugs
• Autoimmune hepatitis 3 Management of ALF involves:
• Extensive investigation for cause
• Liver transplantation as the best current therapy
• Artificial liver support systems, such as therapeutic plasma exchange, for patients with ALF, especially in non-transplant centers 3
• Supportive management in an intensive care unit in a liver transplant center, with timely transfer and active surveillance of infections 5