What are the signs, symptoms, and pathophysiology of liver (hepatic) failure?

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From the Guidelines

Liver failure is a life-threatening condition that requires prompt recognition and management to improve outcomes, with signs and symptoms including fatigue, weakness, nausea, loss of appetite, and abdominal discomfort, progressing to jaundice, ascites, edema, easy bruising and bleeding, mental confusion or encephalopathy, and a distinct sweet-smelling breath (fetor hepaticus) 1.

Pathophysiology of Liver Failure

The pathophysiology of liver failure involves damage to hepatocytes beyond the liver's regenerative capacity, disrupting multiple liver functions including protein synthesis, toxin clearance, bile production, and metabolic regulation 1.

  • The impaired clearance of toxins like ammonia leads to hepatic encephalopathy
  • Decreased production of clotting factors causes coagulopathy
  • Reduced albumin synthesis contributes to edema and ascites
  • Portal hypertension develops as blood flow through the damaged liver becomes restricted, further complicating the condition

Clinical Presentation and Diagnosis

Liver failure can present with a range of signs and symptoms, including:

  • Early signs: fatigue, weakness, nausea, loss of appetite, and abdominal discomfort
  • More severe manifestations: jaundice, ascites, edema, easy bruising and bleeding, mental confusion or encephalopathy, and a distinct sweet-smelling breath (fetor hepaticus) 1
  • Diagnosis is based on a combination of clinical presentation, laboratory tests, and imaging studies

Management and Treatment

Management of liver failure focuses on treating the underlying cause while providing supportive care until the liver recovers or transplantation becomes necessary 1.

  • Treatment may involve:
  • Supportive care, such as fluid and electrolyte management, nutritional support, and management of complications like hepatic encephalopathy and coagulopathy
  • Specific treatments for the underlying cause, such as antiviral medications for viral hepatitis or withdrawal of offending medications in cases of drug-induced liver injury
  • Consideration for liver transplantation in cases of severe liver failure or acute-on-chronic liver failure

From the Research

Liver Failure Signs and Symptoms

  • Acute liver failure (ALF) is a life-threatening disorder characterized by rapid deterioration of liver function, coagulopathy, and hepatic encephalopathy in the absence of pre-existing liver disease 2
  • Signs and symptoms of ALF include altered mentation, disturbed coagulation, and rapid-onset elevation of aminotransferases 3
  • Cerebral oedema and intracranial hypertension are common complications of ALF, and can lead to high morbidity and mortality 4, 5, 6

Pathophysiology of Liver Failure

  • ALF is a rare and dynamic condition, with a broad aetiology and an incompletely understood pathophysiology 4
  • The cause of ALF varies across the world, and common causes include drug toxicity, hepatotropic and non-hepatotropic viruses, herbal and dietary supplements, antituberculosis drugs, and autoimmune hepatitis 2
  • The absence of existing liver disease distinguishes acute liver failure from decompensated cirrhosis or acute-on-chronic liver failure 3

Management of Liver Failure

  • Management of ALF requires critical care and organ support, and frequently early liver transplantation 4, 5
  • Proper identification, prevention, and treatment of complications such as intracranial hypertension and sepsis are critical to optimizing outcomes 4, 5
  • Therapeutic plasma exchange and continuous renal replacement therapy (CRRT) may have a role in the management of ALF, particularly in patients with severe disease 4, 5
  • Liver transplantation is the best current therapy for ALF, and can provide a life-saving alternative to medical management 2, 3, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute liver failure.

Lancet (London, England), 2024

Research

Acute liver failure.

Lancet (London, England), 2019

Research

Acute liver failure: A practical update.

JHEP reports : innovation in hepatology, 2024

Research

Update on the management of acute liver failure.

Current opinion in critical care, 2025

Research

Acute Liver Failure.

Clinics in liver disease, 2017

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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