Makindo Medical Notes

Related Subjects: |Chronic liver disease |Liver Function Tests |Ascites Assessment and Management |Budd-Chiari syndrome |Alcoholism and Alcoholic Liver Disease |Liver Transplantation

Acute Liver Failure (ALF) is an acute episode of primary liver dysfunction in a person without pre-existing chronic liver disease or other systemic illness causing liver disease. In hyperacute cases, the interval from onset to liver failure is a week or less, often due to paracetamol (acetaminophen) toxicity or viral infections such as hepatitis A, B, and E in developing regions. Signs may include coagulopathy, elevated serum transaminases, abnormal bilirubin levels, and altered consciousness, which may progress to coma and death.

Classification: Jaundice to Encephalopathy Time Gap

About Acute Liver Failure (ALF)

• Incidence: Approximately 10 cases per million people annually in developed countries.
• Commonly Affects: Previously healthy adults in their 30s.
• Fulminant Hepatic Failure: Severe liver injury with rapid progression to hepatic encephalopathy within 8 weeks of symptom onset, without pre-existing liver disease. It is potentially reversible if treated promptly.
• Diagnostic Criteria: Hepatic injury of less than 26 weeks' duration, international normalized ratio (INR) > 1.5, altered mental status, and absence of chronic liver disease (except in cases like Wilson's disease, vertically acquired HBV, or autoimmune hepatitis).

Findings in Acute Liver Failure

• Hepatocellular Jaundice: Yellowing of the skin and eyes due to elevated bilirubin.
• Elevated Liver Enzymes: Increased AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels.
• Coagulopathy: Prolonged prothrombin time due to impaired synthesis of clotting factors.
• Encephalopathy: Signs of brain dysfunction ranging from confusion to coma.

Causes of Acute Liver Failure

• Viral Hepatitis (40-70%): Hepatitis A, B, D, C, E; cytomegalovirus (CMV); Epstein-Barr virus (EBV); varicella-zoster virus (VZV).
• Drug-Induced/Toxic Causes (20%): Paracetamol overdose (common in the UK), halothane, isoniazid, phenytoin, sulfonamides, amiodarone, ecstasy.
• Autoimmune Hepatitis: Immune-mediated liver injury.
• Metabolic Diseases: Wilson's disease (copper accumulation), acute fatty liver of pregnancy.
• Vascular Causes: Budd-Chiari syndrome (hepatic vein thrombosis).
• Pregnancy-Related Conditions: HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelet count); screen neonate for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.
• Other Infections: Leptospirosis, yellow fever, severe bacterial infections, amoebic infection.
• Reye’s Syndrome: Rare condition associated with aspirin use in children.
• Unknown Causes: 20-30% of cases have no identifiable cause.

Clinical Features

• History: Exposure to drugs, toxins, or recent infections is crucial.
• Symptoms: Jaundice, bleeding tendencies, hypoglycemia, nausea, vomiting.
• Signs of Encephalopathy:
  • Hepatic flap (asterixis).
  • Fetor hepaticus (musty breath odor).
  • Constructional apraxia (inability to draw simple figures).
• Signs of Chronic Liver Disease: May be absent but can include spider naevi, gynecomastia, palmar erythema.
• Encephalopathy Grading:
  • Grade 1: Disoriented but awake.
  • Grade 2: Confused, lethargic.
  • Grade 3: Stuporous, difficult to arouse.
  • Grade 4: Comatose, unresponsive.

Investigations Summary

• Laboratory Tests:
  • Full blood count (FBC), electrolytes, liver function tests (LFTs), coagulation profile.
  • Arterial blood gases (ABG): May show metabolic acidosis.
  • Toxicology screen: Blood and urine for drugs and toxins.
  • Ammonia levels: Elevated in encephalopathy.
  • Viral serology: HAV IgM, HBV markers (HBsAg, anti-HBc IgM), HCV antibodies, HEV, CMV, HSV, EBV.
  • Autoimmune markers: Antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), liver-kidney microsomal antibody (LKM), soluble liver antigen (SLA), immunoglobulin levels.
  • Wilson’s disease tests: Ceruloplasmin levels, 24-hour urinary copper, slit-lamp examination for Kayser-Fleischer rings.
  • Pregnancy test, HIV status.
• Imaging: Ultrasound of the liver to assess size, texture, and presence of ascites; Doppler ultrasound to evaluate hepatic vasculature for Budd-Chiari syndrome.
• Additional Tests: Consider liver biopsy if diagnosis remains unclear and coagulopathy is corrected.

General Management of Acute Liver Failure

• Supportive Care:
  • Airway, Breathing, Circulation (ABC): Secure airway if encephalopathy grade ≥3.
  • Avoid hypoxemia, hypotension, and hypoglycemia.
  • Monitor vital signs, urine output, and neurological status closely.
  • Manage hypoglycemia with intravenous dextrose (25% initially, then 10% infusion).
  • Treat coagulopathy with vitamin K 5 mg IV; administer fresh frozen plasma (FFP) and platelets if bleeding or prior to invasive procedures.
  • Administer lactulose 30 mL orally three times daily to achieve 2-3 soft bowel movements per day.
• Prevent Complications:
  • Head elevation at 20 degrees to reduce intracranial pressure.
  • Consider mannitol 20% (0.5–1 g/kg IV) if signs of cerebral edema develop.
  • Avoid sedatives and hepatotoxic medications.
  • Maintain electrolyte balance; correct hyponatremia and hypokalemia cautiously.
  • Monitor for and treat infections promptly; prophylactic antibiotics may be considered.
• Consultation and Transfer:
  • Early consultation with a hepatologist or liver transplant center is crucial.
  • Consider transfer to a facility capable of liver transplantation if criteria are met.

Specific Management Based on Cause

• Paracetamol Overdose: Administer intravenous N-acetylcysteine (NAC) immediately, regardless of time since ingestion or serum paracetamol levels.
• Autoimmune Hepatitis: Consider corticosteroids (e.g., prednisolone 40–60 mg/day) after ruling out active infection.
• Mushroom Poisoning (Amanita phalloides): Administer high-dose penicillin G and consider silymarin; early consideration for liver transplantation is essential.
• Pregnancy-Related ALF:
  • Acute Fatty Liver of Pregnancy: Expedite delivery of the fetus.
  • HELLP Syndrome: Immediate delivery is recommended; monitor both mother and neonate closely.
• Wilson's Disease: Urgent evaluation for liver transplantation is often necessary.
• Viral Hepatitis: Supportive care; specific antiviral therapies may be considered in certain cases (e.g., antiviral agents for herpes simplex virus).
• Budd-Chiari Syndrome: Manage with anticoagulation, thrombolysis, or surgical interventions; consider transplantation if liver failure progresses.

Complications and Additional Management

• Hypoglycemia: Monitor glucose levels frequently; administer dextrose as needed.
• Coagulopathy: Administer vitamin K, FFP, and platelets if bleeding occurs or prior to procedures.
• Cerebral Edema: Elevate head, maintain adequate ventilation, consider mannitol or hypertonic saline under specialist guidance.
• Hepatic Encephalopathy:
  • Limit protein intake if indicated.
  • Avoid sedatives and unnecessary medications.
  • Use lactulose to reduce ammonia absorption.
  • Consider rifaximin as an adjunct therapy.
• Infections: High risk due to immunosuppression; maintain strict aseptic techniques and monitor for signs of infection.
• Renal Failure: Monitor renal function; renal replacement therapy may be necessary.
• ICU Care: Patients with encephalopathy grade 3 or higher should be managed in an intensive care setting.

References

• EASL Clinical Practice Guidelines on the Management of Acute (Fulminant) Liver Failure, 2017
• Acute Liver Failure - New England Journal of Medicine, 2013