Overview

Acute liver failure (ALF) is a rare but life-threatening condition characterized by the rapid deterioration of liver function in individuals without pre-existing liver disease. It typically occurs within days or weeks and is marked by sudden onset of jaundice, coagulopathy (problems with blood clotting), and hepatic encephalopathy (confusion or altered mental state). Unlike chronic liver failure, which develops gradually over months or years, acute liver failure progresses quickly and can lead to serious complications like brain swelling, bleeding disorders, and multi-organ failure. Prompt medical intervention is crucial, and treatment often requires intensive care or even liver transplantation.

Causes

Acute liver failure can be caused by a wide range of factors, including medications, infections, and underlying medical conditions. The most common causes include:

• Drug-induced liver injury: Acetaminophen (paracetamol) overdose is the leading cause of ALF in many countries. Other medications, including certain antibiotics, anti-epileptic drugs, and herbal supplements, can also cause liver toxicity.
• Viral hepatitis: Hepatitis A, B, and E viruses can cause acute liver failure, especially in regions with high prevalence of these infections.
• Autoimmune hepatitis: The body's immune system may attack liver cells, leading to rapid liver dysfunction.
• Toxins: Exposure to toxic substances such as poisonous mushrooms (Amanita phalloides), industrial chemicals, or other hepatotoxic agents can trigger ALF.
• Ischemic hepatitis: Severe drop in blood flow to the liver due to heart failure or shock can result in liver injury.
• Metabolic disorders: Rare inherited conditions like Wilson’s disease can cause sudden liver failure, especially in younger individuals.
• Cancer-related causes: Acute liver failure can also result from rapid spread of cancer to the liver.
• Unknown causes: In a significant number of cases, no clear cause (indeterminate ALF) can be identified despite thorough evaluation.

Symptoms

The symptoms of acute liver failure develop rapidly and worsen quickly. Common symptoms include:

• Jaundice: Yellowing of the skin and eyes due to high bilirubin levels.
• Fatigue and weakness: Generalized tiredness and reduced energy levels.
• Abdominal pain: Discomfort or pain, particularly in the upper right quadrant of the abdomen.
• Nausea and vomiting: Frequent gastrointestinal symptoms are common in the early stages.
• Confusion or altered mental state: Hepatic encephalopathy leads to difficulty concentrating, confusion, personality changes, or even coma in advanced stages.
• Bleeding tendency: Easy bruising or excessive bleeding due to impaired clotting factor production.
• Swelling: Fluid retention leading to swelling in the abdomen (ascites) or legs.
• Foul-smelling breath: Fetor hepaticus, a musty odor of the breath, may develop in severe cases.

Diagnosis

Diagnosing acute liver failure requires a combination of clinical evaluation, laboratory testing, and imaging studies to confirm liver dysfunction and determine the underlying cause:

• Medical history and examination: A detailed review of recent medication use, drug or toxin exposure, viral illnesses, and family history is conducted along with physical examination.
• Liver function tests (LFTs): Elevated levels of liver enzymes (ALT, AST), high bilirubin, and low albumin levels indicate liver dysfunction.
• Coagulation tests: Prolonged prothrombin time (PT) and increased INR reflect impaired blood clotting capacity.
• Serum ammonia: Elevated ammonia levels are often found in hepatic encephalopathy.
• Viral hepatitis panels: Testing for hepatitis A, B, C, D, and E viruses helps identify infectious causes.
• Imaging studies: Ultrasound or CT scans assess liver size, blood flow, and exclude obstructive causes like bile duct blockage.
• Autoimmune and metabolic screening: Tests for autoimmune markers and metabolic disorders like Wilson’s disease may be required.
• Liver biopsy: In select cases, a liver biopsy helps establish a definitive diagnosis when other tests are inconclusive.

Treatment

Treatment of acute liver failure focuses on supportive care, managing complications, and addressing the underlying cause. Treatment typically occurs in an intensive care setting:

• Hospitalization: Immediate admission to an intensive care unit (ICU) is required for close monitoring and management.
• Medications:
  • Antidotes: N-acetylcysteine (NAC) is used for acetaminophen overdose.
  • Antivirals: In cases of hepatitis B, antiviral therapy may be administered.
  • Immunosuppressants: Autoimmune hepatitis may require corticosteroids.
  • Supportive medications: Drugs to manage encephalopathy, control bleeding, and maintain blood pressure are commonly used.
• Liver transplantation: In severe or non-reversible cases, liver transplant offers the only chance for survival. Early evaluation and listing for transplant are critical.
• Management of complications: Intensive care includes treatment of cerebral edema, infections, kidney dysfunction, and metabolic imbalances.

Prognosis

The prognosis of acute liver failure varies depending on the cause, severity, and timely initiation of treatment. Some cases, especially those due to acetaminophen overdose or hepatitis A, have high chances of full recovery with appropriate treatment.

Without prompt intervention, acute liver failure carries a high risk of mortality due to complications like brain swelling, multi-organ failure, and sepsis. Liver transplantation has significantly improved survival rates, with many patients achieving excellent long-term outcomes after surgery. Early recognition, aggressive supportive care, and access to specialized liver centers are crucial for improving survival and recovery in individuals with acute liver failure.