Acute liver failure

Question 1

What are the 3 criteria that define ALF?

Answer 1

-rapid development (< 26wks)
-hepatocellular dysfunction (jaundice, markedly elevated LFTs)
-abnormal liver synthetic function w/ INR > 1.5
-encephalopathy
-absence of prior history of liver disease

Question 2

What are some examples of causes of ALF?

Answer 2

-viral hepatitis
-drug induced
-toxin induced
-metabolic errors
-ischemia
-there are other rare causes

Question 3

What is the icterus-encephalopathy interval (IEI)?

Answer 3

interval between jaundice and encephalopathy w/ or w/o coagulopathy
-also the interval between acute hepatic injury and liver failure

Question 4

What are the icterus-encephalopathy interval (IEIs) that define hyperacute, acute, and sub-acute ALF?

Answer 4

-hyperacute = IEI </= 7 days
-acute = IEI </= 4 weeks
-subacute = IEI > 5 weeks to < 12 weeks

Question 5

What are the major complications in ALF that typically lead to death?

Answer 5

-cerebral edema (most common)
-seizures
-infections (up to 90%)
-bleeding/coagulopathy
-renal failure (40-80%)

Question 6

Is renal failure more or less frequent in ALF d/t acetaminophen overdose?

Answer 6

more frequent (up to 70% compared to 30% in other causes)

Question 7

Hyperammonemia levels lead to changes in which neuroglial cell type?

Answer 7

astrocytes - they start to swell

Question 8

What is the greatest source of circulating ammonia?

Answer 8

glutamine metabolism in the intestinal epithelium
-glutaminase coverts glutamine to glutamate and ammonia

Question 9

What presenting ammonia level in ALF has been shown to predict mortality?

Answer 9

> 124 mmol/L

Question 10

What role do astrocytes play in the the brain (and why is this important in ALF)?

Answer 10

they are an integral component of blood brain barrier, so ammonia accumulation in them leads to alterations in the barrier permeability

Question 11

What electrolyte derangement along w/ hyperammonia induces brain edema?

Answer 11

hyponatremia
-hypernatremia seems to be protective

Question 12

What acid/base alteration can worsen hepatic encephalopathy?

Answer 12

alkaline pH was found to drive ammonia into astrocytes, worsening encephalopathy

Question 13

What are the goals for ICP and CCP in ALF?

Answer 13

ICP < 2mmHg
CCP > 50mmHg

Question 14

What ICP and CCP values are contraindications to liver transplant?

Answer 14

-prolonged ICP > 40 for > 2hrs
-CCP < 50

Question 15

Which muscle relaxants for intubation have prolonged elimination in liver failure?

Answer 15

rocuronium
vecuronium
pancuronium

Question 16

Which glucose derangement is most commonly seen in ALF?

Answer 16

hypoglycemia

Question 17

What future liver remnant post-hepatectomy is needed to prevent post-hepatectomy liver failure in an otherwise healthy liver? In a pt w/ underlying liver disease?

Answer 17

-25%
-40%

Question 18

What are the leading causes of death in ALF?

Answer 18

-cerebral edema
-elevated ICPs

Question 19

What are the caloric and protein requirements for patients w/ ALF?

Answer 19

• 25-40kcal/kg/day
• 0.8-1.2g/kg/day

Question 20

What medication should be given to help improve HBV-associated ALF outcomes?

Answer 20

lamivudine

Question 21

What medication should be given to help improve HSV-associated ALF outcomes?

Answer 21

acyclovir

Question 22

What medication should be given to help improve CMV-associated ALF outcomes?

Answer 22

ganciclovir

Question 23

What are the King’s College Criteria for acetaminophen associated ALF requiring transplant?

Answer 23

-pH < 7.3 after resuscitation
or all of the following
-INR > 6.5
-creatinine > 3.4
-grade 3-4 encephalopathy

Question 24

What are the King’s College Criteria for non-acetaminophen associated ALF requiring transplant?

Answer 24

-INR > 6.5
or any 3 of the following
-age < 10 or > 40
-INR > 3.5
-bilirubin > 17.6
-encephalopathy developing 7+ days after jaundice
-etiology other than HAV/HBV

Question 25

What components make up a MELD score?

Answer 25

-bilirubin
-INR
-creatinine

Question 26

What MELD score is accepted as criteria to pursue transplant?

Answer 26

> 30

Question 27

What should be used first line for pain and agitation in post-op transplant pts?

Answer 27

fentanyl
-rapid on and short duration

Question 28

What should be used first line for sedation in post-op transplant pts?

Answer 28

dexmedetomidine
-alpha 2 adrenoreceptor agonist
-use w/ caution in pts w/ hypotension and bradycardia

Question 29

What can cause sustained delirium and encephalopathy in a post-transplant pt?

Answer 29

-poor functioning of liver transplant graft
-infection
-intracranial hemorrhage
-cerebral ischemia
-seizures
-immunosuppressant toxicity

Question 30

What is the MOA for N-acetylcysteine?

Answer 30

replenishes reduced glutathione stores in the liver
-toxic acetaminophen metabolites deplete these stores

Question 31

When should N-acetylcysteine be used in ALF?

Answer 31

-acetaminophen induced liver failure
-provides a survival benefit (d/t anti-inflammatory properties) for all causes of ALF if given before G3-4 encephalopathy

Question 32

What are risk factors for intracranial hypertension in ALF?

Answer 32

-shorter symptom to encephalopathy interval
-higher grades of encephalopathy
-younger age
-vasopressor use
-renal impairment
-sustained arterial ammonia > 150-200

Question 33

What causes the intracranial hypertension seen in ALF?

Answer 33

raised ammonia levels leading to encephalopathy, cerebral edema, and intracranial hypertension

Question 34

What is the treatment for mushroom induced ALF?

Answer 34

IV silibinin
-milk thistle or silymarin
-give w/ PCN G and NAC