What are the causes and management of acute liver failure (ALF)?

From the Guidelines

Acute liver failure requires immediate hospitalization in an intensive care unit and transfer to a liver transplant center, with administration of N-acetylcysteine (NAC) for acetaminophen overdose and consideration of liver transplantation as the definitive treatment. The management of acute liver failure involves identifying and removing the underlying cause, providing supportive care with IV fluids, correcting coagulation abnormalities, and monitoring for complications 1.

Key Considerations

• Early recognition and prompt management of liver failure and its complications may improve outcomes 1
• NAC should be administered for acetaminophen overdose at a loading dose of 150 mg/kg over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1
• Lactulose and rifaximin may help manage hepatic encephalopathy [@Example@]
• Blood glucose should be maintained above 70 mg/dL with dextrose infusions if needed [@Example@]
• Patients require close neurological monitoring, infection surveillance with prophylactic antibiotics in some cases, and management of cerebral edema 1

Diagnosis and Treatment

The diagnosis of acute liver failure is based on the occurrence of encephalopathy and hepatic synthetic dysfunction within 26 weeks of the first symptoms of liver disease in a patient without evidence of chronic liver disease 1. The treatment of acute liver failure involves a multidisciplinary approach, including critical care, emergency medicine, pharmacists, nurses, advanced practice providers, and dietitians 1.

Prognosis and Outcome

The prognosis of acute liver failure is poor, with high mortality rates if left untreated 1. Liver transplantation is the definitive treatment for many cases of acute liver failure, and early evaluation and listing for transplantation are essential 1.

From the FDA Drug Label

Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.

The drug N-acetylcysteine (IV) is used to treat acetaminophen overdose, which can cause acute liver failure.

• The effectiveness of N-acetylcysteine depends on early administration, within 16 hours of the overdose.
• N-acetylcysteine works by maintaining or restoring glutathione levels or by acting as an alternate substrate for conjugation with the reactive metabolite. 2

From the Research

Definition and Causes of Acute Liver Failure

• Acute liver failure (ALF) is a rare critical illness with high mortality, requiring early recognition and effective initial management 3.
• ALF can result from a wide variety of causes, including paracetamol-induced hepatotoxicity, acetaminophen overdose, viral hepatitis, drug-induced liver injury, Wilson's disease, and autoimmune hepatitis 4.
• The definition of ALF includes neurologic dysfunction, an international normalized ratio ≥ 1.5, no prior evidence of liver disease, and a disease course of ≤ 26 weeks 5.

Diagnosis and Treatment of Acute Liver Failure

• Diagnosis of ALF involves recognizing the common etiologies, including acetaminophen overdose, and using laboratory and imaging tests to establish the diagnosis 4.
• Administration of antidotal N-acetyl cysteine at first recognition is key in managing ALF, particularly in cases of paracetamol-induced hepatotoxicity 3.
• N-acetylcysteine (NAC) is used to prevent hepatotoxicity and improve outcomes in patients with ALF, with its main mechanism of action being to maintain intracellular glutathione stores to detoxify the electrophilic APAP metabolite, NAPQI 6.
• Patients with acute liver failure may be candidates for orthotopic liver transplantation, with one-year survival after emergency liver transplantation being 70% 7.

Management and Prognosis of Acute Liver Failure

• Management of ALF involves early recognition, effective initial management, and supportive care, including stabilization, monitoring, and treatment of complications such as encephalopathy, coagulopathy, infectious processes, renal injury, and hemodynamic instability 5.
• Prognostic criteria are applied to identify patients for emergency liver transplantation, and candidates for surgery are prioritized on waitlisting schemes 3.
• Outcomes for patients with ALF have improved dramatically over the last three decades, but mortality remains unacceptable, highlighting the need for further advances in care 3.