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

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Last updated: May 30, 2025View editorial policy

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From the Guidelines

Acute liver failure is most commonly caused by acetaminophen-induced hepatotoxicity, accounting for 22% of cases, followed by hepatitis A and B infections, and other drugs or toxic agents. The causes of acute liver failure (ALF) can be diverse, and identifying the underlying reason is crucial for guiding specific management and predicting outcomes 1.

Common Causes of ALF

  • Acetaminophen-induced hepatotoxicity, whether intentional or not, is the leading cause of severe ALF and an indication for emergency liver transplantation 1.
  • Hepatitis A and B infections account for 14.6% of ALF cases 1.
  • Other drugs, such as antimicrobial and antiepileptic agents, statins, and various toxic agents like herbal supplements, cocaine, ecstasy, or mushrooms, cause ALF in 9.4% and 4.8% of cases, respectively 1.

Less Frequent Causes of ALF

  • Autoimmune hepatitis, Wilson’s disease, and metabolic diseases are less common causes, accounting for 28.8% of patients on the liver transplant waiting list 1.
  • Vascular issues, malignant infiltration, and other rare conditions can also lead to ALF.

Importance of Early Recognition

Early recognition of the cause of ALF is vital to guide potential specific management and predict its outcome 1. Abdominal Doppler ultrasound and echocardiography should be performed rapidly to exclude chronic liver disease and verify the permeability of vessels 1. Prompt identification and treatment of the underlying cause can significantly impact patient outcomes, with transplant-free survival rates varying widely depending on the etiology of ALF.

From the Research

Causes of Acute Liver Failure

The causes of acute liver failure can be categorized into several groups, including:

  • Viral infections, which remain a significant cause of ALF in many developing nations 2
  • Drug-induced liver injury, including acetaminophen toxicity, which is the leading cause of ALF in the Western world 2, 3, 4
  • Hepatic ischaemia 3
  • Autoimmune hepatitis 3, 5
  • Wilson's disease 5
  • Herbal and dietary supplements 3
  • Acetaminophen overdose, which has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care 4

Specific Causes and Their Impacts

  • Acetaminophen (paracetamol) use has been associated with severity and outcomes in patients with viral hepatitis-associated acute liver failure, with evidence suggesting that concurrent APAP use may negatively impact outcomes compared with little or no APAP exposure 6
  • Viral hepatitis, including hepatitis A, B, Epstein-Barr virus, and herpes simplex virus, can lead to ALF, with APAP use potentially exacerbating liver injury 6
  • The use of APAP to treat prodromal hepatitis symptoms is common, but its impact on liver injury in AVH-induced ALF is not well understood, highlighting the need for prospective studies on the safest and effective dose of APAP to use in patients with AVH 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Viral etiologies of acute liver failure.

World journal of virology, 2024

Research

Acute liver failure.

Lancet (London, England), 2019

Research

Acute liver failure including acetaminophen overdose.

The Medical clinics of North America, 2008

Research

Acute Liver Failure.

Seminars in respiratory and critical care medicine, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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