Acute Liver Failure: Pathogenesis and clinical findings

Acute Liver Failure: Pathogenesis and clinical findings
Authors: Juliette Hall Reviewers: Vina Fan, Ben Campbell, Mayur Brahmania* * MD at time of publication
Acetaminophen Overdose
Accumulation of toxic NAPQI (a metabolite of acetaminophen)
NAPQI binds hepatocellular proteins
(see Acetaminophen Overdose: pathogenesis and clinical findings slide)
Drug-induced liver injury
Metabolism of drugs by the liver can produce reactive drug metabolites
Intracellular stress, mitochondrial injury, or immune response
Viral Hepatitis (i.e. HAV, HBV, HEV, HSV)
Acute infection or infection flare provokes an immune response against infected hepatocytes
Autoimmune Hepatitis
Autoimmune antibodies attack hepatocytes (see Auto-immune Hepatitis (AIH) slide)
Ischemia (i.e. from shock)
↓ O2 delivery to the liver
Hepatocellular hypoxia
Wilson’s Disease
Heritable mutation in the ATP7B gene
↓ Biliary excretion of copper
Hepatic copper accumulation injures hepatocytes (see Wilson’s Disease slide)
Accelerated rate of hepatocellular necrosis or apoptosis
Hepatocyte death exceeds regeneration such that liver function is compromised within a short amount of time
Acute Liver Failure
An illness of <26 weeks duration in the absence of pre-existing cirrhosis, characterized by INR ≥1.5 and evidence of altered mentation (hepatic encephalopathy) Injured hepatocytes leak hepatic enzymes (AST, ALT, GGT) into circulation ↑ Liver enzymes Hepatocellular inflammation Stimulation of foregut autonomic nerves Right upper quadrant pain ↓ Toxin metabolism Toxins build up and activate microglial cells (brain macrophage) Oxidative stress and cerebral edema Hepatic encephalopathy Characteristic set of neuropsychiatric symptoms (see Hepatic Encephalopathy slide) ↓ Hepatocellular function and number ↓ Complement protein synthesis ↓ Ability to clear immune complexes and activate B cells Accumulation of pigmented bilirubin ↓ Synthesis of coagulation factors ↑ INR ↓ Conjugation of bilirubin by the liver and ↓ transport into bile for excretion ↑ Serum bilirubin Jaundice Infection Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published November 15, 2022 on