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Acute-on-chronic liver failure (ACLF)

Overview

Acute-on-chronic liver failure (ACLF) is a severe and life-threatening condition characterised by the rapid deterioration of liver function in patients with pre-existing chronic liver disease. ACLF is distinct from general liver failure as ACLS exhibits a higher speed of onset, i.e., a rapid decline in liver function—whereas general liver failure can be either acute (rapid loss of liver function) or chronic (gradual loss of liver function)—causes multiple organ failure (kidney, liver, heart, brain, lungs) by inducing intense systemic inflammation (across the body).

ACLF typically occurs in individuals who have preexisting chronic liver disease, such as cirrhosis. The acute deterioration of liver function can be triggered by various factors, including:

  • Infections:
    • Bacterial infections: Spontaneous bacterial peritonitis (SBP), pneumonia, or urinary tract infections can trigger ACLF.
    • Viral infections: Hepatitis viruses (e.g., Hepatitis B, Hepatitis C) can trigger ACLF.
    • Fungal infections: In immunocompromised individuals with cirrhosis, fungal infections can trigger ACLF.
  • Alcohol abuse: Excessive alcohol consumption or sudden binge drinking can lead to liver injury, precipitating ACLF in patients with pre-existing liver disease.
  • Hepatotoxic drugs: Certain medications (e.g., acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs)) can worsen liver function.
  • Gastrointestinal bleeding: Excessive bleeding from varices (due to portal hypertension) or gastric ulcers can lead to ACLF.
  • Renal (kidney) failure: Pre-existing kidney issues or acute kidney injury (AKI) can worsen liver function, resulting in ACLF.
  • Metabolic disturbances: Electrolyte imbalances, dehydration, or hyperammonemia (a metabolic condition associated with high levels of ammonia in the blood) can exacerbate liver dysfunction.
  • Systemic inflammatory response: Conditions like sepsis, shock, or pancreatitis can trigger a systemic inflammatory response, thereby contributing to liver failure.
  • Hepatic encephalopathy: This condition can complicate the underlying liver disease, leading to ACLF.
  • Presence of comorbidities: Comorbidities, like kidney dysfunction (renal failure), cardiovascular disease, and metabolic disorders can contribute to the worsening of ACLF.
  • Poor nutrition: Malnutrition, which is common in liver disease, can weaken the body’s ability to recover from stressors like infection or injury, thereby enhancing susceptibility to ACLF.
  • Older age: Older patients with chronic liver disease are at higher risk of developing ACLF.

The symptoms of ACLF are related to acute deterioration of liver function as well as the multi-organ failure that can accompany it; these include:

  • Jaundice: This condition occurs due to bilirubin accumulation.
  • Ascites: Fluid accumulation in the abdomen due to liver dysfunction and portal hypertension.
  • Hepatic encephalopathy: Confusion, altered mental status, and in severe cases—coma—due to the inability of the liver to detoxify toxic substances in the blood.
  • Hepatorenal syndrome: Acute kidney failure, marked by low urine output and high levels of creatinine.
  • Gastrointestinal bleeding: Characterised by vomiting blood (hematemesis) or black, tarry stools (melena) due to variceal rupture or ulcers.
  • Fever and infection signs: In ACLF cases triggered by infection, fever, chills, and increased white blood cell counts may be observed.
  • Fatigue and weakness: Generalised malaise and lethargy due to liver and multi-organ failure.
  • Hypotension: Low blood pressure, often due to septic shock or liver dysfunction.

The diagnosis of ACLF is clinical, supported by laboratory tests and imaging. Key diagnostic steps include:

  • Clinical criteria:
    • History of chronic liver disease: The patient typically has a history of chronic liver disease, e.g., cirrhosis.
    • Acute deterioration of liver function: Sudden worsening of liver function, often identified by increasing bilirubin levels and INR (coagulation disorders), and worsening encephalopathy.
  • Blood Tests:
    • Liver function tests: Elevated AST, ALT, and bilirubin levels.
    • Coagulation tests: INR >1.5.
    • Kidney function tests: Creatinine and blood urea nitrogen (BUN) levels to assess renal (kidney) function.
    • Complete blood count (CBC): To check for infection or bleeding.
    • Arterial blood gas (ABG): To assess metabolic acidosis or respiratory dysfunction.
    • Serum ammonia: To assess hepatic encephalopathy.
  • Imaging:
    • Ultrasound: To assess the liver, portal vein, and presence of ascites or masses.
    • CT or MRI: To evaluate liver structure, complications (e.g., tumours, abscesses), and other organ involvement.
    • Endoscopy: To assess oesophageal varices.
  • Assessment of organ function: Multisystem organ failure (kidneys, lungs, cardiovascular system) is often evaluated, as ACLF can involve multiple organs.

The treatment of ACLF focuses on managing the underlying liver disease, treating the acute precipitating factors, and addressing multi-organ failure. The approach includes:

  • Treating the underlying cause(s):
    • Infections: Antibiotics, antivirals, or antifungals depending on the causative pathogen.
    • Alcohol: Systems and medications to enable complete cessation of alcohol consumption.
    • Discontinuation of hepatotoxic drugs: Stopping any drugs or substances that may have contributed to ACLF.
  • Supportive care:
    • Nutritional support: Adequate caloric intake, often through enteral feeding or parenteral nutrition if necessary.
    • Management of ascites: Diuretics (spironolactone, furosemide) to manage fluid accumulation.
    • Hemodynamic support: Intravenous fluids, vasopressors, and monitoring to stabilize blood pressure and manage septic shock if present.
    • Liver Support:
      1. Liver transplantation: The definitive treatment for patients with ACLF who have end-stage liver disease.
      2. Artificial liver support systems: In some cases, devices like the molecular adsorbent recirculating system (MARS) may provide temporary liver support.
  • Management of complications:
    • Lactulose and rifaximin: These drugs reduce ammonia levels in the blood, thereby managing hepatic encephalopathy.
    • Renal replacement therapy: Dialysis may be required for patients with acute kidney failure (hepatorenal syndrome).
    • Endoscopic treatments: For variceal bleeding.
  • Critical care: Intensive care management, including mechanical ventilation, continuous monitoring, and multi-organ support are needed for ACLF patients as the condition can rapidly progress to liver failure.
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