Acute liver failure – etiology, pathogenesis, and clinical manifestations.
Acute liver failure is rapid loss of liver function, characterized by severe hepatocellular dysfunction within days to weeks, leading to coagulopathy (INR ≥1.5) and hepatic encephalopathy, in a patient without pre-existing liver disease.
Etiology
Drugs and toxins (most common in Western countries)
- Acetaminophen (paracetamol) overdose (most frequent).
- Other drugs: isoniazid, valproic acid, halothane.
- Toxins: Amanita phalloides (mushroom poisoning).
Viral hepatitis
- HBV (most common viral cause).
- HAV, HEV (especially in pregnant women).
- HSV (rare).
Ischemic injury
- Massive hypotension (“shock liver”).
- Hepatic vein thrombosis (Budd-Chiari syndrome).
Other causes
- Autoimmune hepatitis.
- Wilson’s disease (in adolescents, young adults).
- Acute fatty liver of pregnancy.
Pathogenesis
- 1 Massive hepatocyte necrosis
- Direct toxic injury (e.g., acetaminophen metabolites) or immune-mediated destruction (e.g., viral hepatitis).
- 2 Loss of hepatic synthetic and detoxification functions
- Decreased production of coagulation factors → coagulopathy.
- Impaired ammonia detoxification → hyperammonemia → cerebral edema → encephalopathy.
- 3 Systemic inflammatory response and multi-organ failure
- Impaired vascular tone → hypotension.
- Renal dysfunction (hepatorenal syndrome).
- Increased susceptibility to infections.
Clinical manifestations
General symptoms
- Profound fatigue, weakness.
- Nausea, vomiting.
- Jaundice (can be severe).
Coagulation abnormalities
- Easy bruising.
- Mucosal bleeding.
Hepatic encephalopathy
- Mental status changes: confusion, lethargy → stupor → coma.
- Asterixis (“flapping tremor”).
- Cerebral edema → increased intracranial pressure.
Other features
- Ascites (may occur but less prominent than in chronic liver disease).
- Hypoglycemia (due to impaired gluconeogenesis).
- Renal failure (hepatorenal syndrome).
- Infections (sepsis risk).