Acute Liver Disease

Question 1

What are the different liver failures?

Answer 1

Question 2

Acute Liver Failure (ALF) is Defined As

Answer 2

• No pre-existing liver disease
– Exceptions: Wilson’s disease, Autoimmune hepatitis, Hepatitis B
• INR > 1.5
• Any degree of mental alteration • Illness <26 weeks duration

Question 3

What is the presentation for Acute Liver Failure?

Answer 3

• Rare Presentation
• 2000 cases per year in the US
• 60-75% overall survival
• About 4% of listings for orthotopic liver transplantation in US

Question 4

Key In Evaluation ALF is Assessing Etiology for Treatment

Answer 4

• Search for etiology
– Acetaminophen use
– Supplement use
– Substance abuse
– Suicide attempt
– Depression

• Evaluate for risk factors for ALF
– Pregnancy
– Travel
– Immune suppression
– Chemotherapy
– Autoimmune diseases

• Assess for conditions that impact decision on liver transplant
– Known chronic liver disease
– Active and dependent alcohol or substance
abuse
– History of recent cancer
– Severe congestive heart disease or respiratory co-morbidity

• Calculate interval from jaundice to encephalopathy

Question 5

Timing of Acute Liver Failure Predicts Survival Without Transplant

Answer 5

Timing of Acute Liver Failure Predicts Risk of Cerebral Edema

Question 6

Patient Can Have Acetaminophen (APAP) Toxicity Despite Negative Level

Answer 6

• Diagnosis can be missed when history obscure or patient comatose on arrival
• Characteristic high AST or ALT and low bilirubin
• Criteria
– Ingestion > 4 grams
– Any positive APAP level
– ALT >1000 (91%); ALT > 3500 (58%)
• Acetaminophen Toxicity is the Most Common Etiology of ALF
• Acetaminophen Toxicity Related to Injury from NAPQI

Question 7

Acetaminophen Toxicity is the Most Common Etiology of ALF

Question 8

Acetaminophen Toxicity Related to Injury from NAPQI

Answer 8

Question 9

N- Acetylcysteine Augments Glutathione Stores and Protect Hepatocytes from NAPQI

Answer 9

Question 10

Amanita Phalloides Mushroom Ingestion is a Cause of ALF

Answer 10

• > 10,000 species of mushrooms
• Amatoxin Poisoning Related to α- Amanitin
  
  • α-Amanitin-can be measured in blood, urine, gastric aspirate
  • Consumed mushrooms are absorbed via the GI tract and enter portal circulation
    
    • Enter into hepatocytes and concentrated within cell
    • Bind to RNA polymerase and halts intracellular protein production
    • Hepatocyte Apoptosis
    • Also excreted into biliary tract → gut → repeat enterohepatic circulation → recurrent exposure
• Amatoxin Poisoning Treatment Depend on Availability and Severity
  
  • Activated charcoal- interrupts enterohepatic circulation and limit ongoing exposure
  • Silibinin, Penicillin G- decreases hepatocyte uptake of toxin from portal circulation
  • NAC- antioxidant effect

Question 11

Wilson Disease is a Rare Disorder of Copper Metabolism that Can Lead to Liver Failure

Answer 11

• Autosomal recessive
• Defect in ATP7B gene that encodes for a copper transporting ATPase
  
  • Export copper from the hepatocyte into the bile canaliculus and also incorporates Cu into ceruloplasmin
• Absence causes copper accumulation within hepatocytes and in extra hepatic organs
• Fulminant Wilson Disease is Fatal Without Liver Transplant
  
  • Coombs-negative hemolytic anemia
  • Neurologic symptoms prior to the onset of acute liver failure
  • Kayser-Fleisher rings
  • A ratio of AST to ALT of greater than two
  • A normal or subnormal alkaline phosphatase
  • A ratio of alkaline phosphatase (int. unit/l) to total bilirubin (mg/dl) of less than four

Question 12

Etiology and Outcome: Good Prognosis- 60% Spontaneous Survival

Answer 12

• Acetaminophen
• Hepatitis A
  Ischemia/Shock
• Pregnancy

Question 13

Etiology and Outcome: Poor Prognosis- 30% Spontaneous Survival

Answer 13

• Drugs
  Indeterminate
• Autoimmune hepatitis
• Hepatitis B
  Wilson’s disease

Question 14

_____ Predicts Prognosis and Need for Liver Transplant

Answer 14

King’s College Criteria

Question 15

______ Index More Accurate Predictor Than ______ and _______

Answer 15

ALFSG Index More Accurate Predictor Than King’s Criteria and MELD Score

Question 16

Complications of ALF

Answer 16

Question 17

Management of ALF

Answer 17

Question 18

Management of ALF x 2

Answer 18

Question 19

Hepatic Encephalopathy: Cerebral Edema Is Related to Hyperammonemia

Answer 19

• HE is a defining feature of ALF
• Cerebral edema leading to herniation is an important cause of death in ALF
• Mechanism likely multifactorial
  
  • Increased ammonia production and uptake by brain astrocytes
  • Accumulation of glutamine (osmotically active)
  • Passive influx of water
  • Rapid swelling of astrocytes
• Different from chronic liver disease
  
  • Slower rate of glutamine accumulation allowing astrocytes to maintain osmotic balance- cerebral edema not seen

Question 20

How is Hepatic Encephalopathy Assessed?

Answer 20

Hepatic Encephalopathy is Assessed Using the West Haven Criteria

Question 21

Management of Cerebral Edema Includes Maintaining Cerebral Perfusion and Decreasing Ammonia

Answer 21

Question 22

Renal Dysfunction Occurs in Up to 33% of Patients

Answer 22

Question 23

Renal Dysfunction Occurs in Up to 33% of Patients

Answer 23

Question 24

Management of ALF in Hepatorenal Syndrome

Answer 24

• Management

– Volume Repletion

– Vasopressors, MAP (mean arterial pressure) > 80 to maintain CPP (cerebral perfusion pressure)

– Echocardiography

– Consideration of adrenal insufficiency

Question 25

Institution of CRRT

Answer 25

Question 26

Timing of Acute Liver Failure Predicts Risk of Cerebral Edema

Answer 26