CM- Acute Hepatitis

Question 1

When is hepatotoxicity dose-related?

What is an example of this type of drug?

Answer 1

when every individual ingesting a sufficient amount manifests hepatotoxicity

Ex. acetaminophen

Question 2

What is hepatic injury dependent on in idiosyncratic drug-induced liver injury?

Answer 2

Host factors.
Genetics: gender, metabolizing enzymes, differences in immune responsiveness
Acquired: nutritional status, concomitant conditions, other medications, alcohol

Question 3

What determines the clinical presentation of drug induced hepatitis?

Answer 3

The pattern of enzyme change:
1. hepatocellular
2. cholestatic
3 .mixed

Question 4

What are the 3 major etiologic categories for MILD acute hepatitis?

Answer 4

1. Early stages of Hep A-E, CMV, EBV
2. drugs and toxins
3. autoimmune

Question 5

Why is alchohol not included in the differential diagnosis of true acute hepatitis?

Answer 5

It is an acute exacerbation of underlying chronic liver disease

Question 6

How is the etiology of acute hepatitis determined?

Answer 6

1. History (look for risk factors, travel, etc)
2. serological tests (autoimmune, viral)
3. imaging (gallstones, secondary dilation)

Question 7

Viral serologic tests for acute hepatitis are appropriate unless there is evidence of what lab finding?

Answer 7

Elevated LD equal to AST. This is a sign of ischemia (cocaine, heart failure, hyperthermia)

Question 8

When serologic studies are negative what test should you consider?

Answer 8

US to check for gallstones and secondary dilation

Question 9

If the viral serologic test are all negative and the sonogram shows no obstructions, what is the next thing you want to consider?

Answer 9

Look for :

SMA, ANA and LKM1 antibodies

Question 10

If a patient has mild acute hepatitis (asymptomatic with slightly elevated liver enzymes) what do you do?

Answer 10

“watchful waiting” - confirm the findings before trying to figure out the etiology.

Question 11

What stimuli are going to have asymptomatic or mild liver disease? Which are going to have more severe acute disease?
What are unlikely to present as an acute process?

Answer 11

Asymptomatic/Mild: viruses, drugs/toxins, autoimmune

Severe: obstruction, ischemia

Chronic: genetic disorder (A1AT, Wilson, hemochromatosis), alcohol

Question 12

How long does it take for AST and ALT to return to normal after ischemia, choledolithiasis, and acetaminophen toxicity stimuli are removed?

How long does it take for AST and ALT to return to normal after viral hepatitis?

Answer 12

Ischemia, choledolithiasis, acetaminophen toxicity return quickly (half life of the enzymes)

Viral takes longer because it is the immune response, not the virus itself causing the damage

Question 13

How does severe liver damage cause hepatic encephalopathy?

Answer 13

Portal venous blood enters systemic circulation directly without passing through the liver.

The unaltered metabolites like ammonia and glutamine change the brain osmolarity and water content, neurotransmitter levels and energy metabolism

Question 14

Are you more likely to get cerebral edema and intra-cranial hypertension in acute or chronic liver disease?

Answer 14

Acute - this is because of degree, not mechanism

Also in acute, ammonia clearance and metabolism is compromised. Glutamine also accumulates.

A rapid change will cause brain shrinkage quickly

Question 15

What drug is the most common etiology for acute liver failure? What determines the hepatotoxicity?

Answer 15

Acetominophen

The level between 4 and 24 hours after ingestion predicts hepatotoxicity

Question 16

What are the 3 pathways by which acetaminophen is metabolized?

Answer 16

1. Glucuronidation (same as bilirubin)
2. Sulfation
3. p450s produce NAPQI (radical toxic metabolite)
   Glutathione S-transferase (GSH) can take NAPQI to make it innoculous but if glutathione is depleted, NAPQI will form a hepatotoxic covalent adduct

Question 17

What decreases glucuronidation of acetaminophen?

What else can increase the flux down the hepatotoxic pathway?

Answer 17

Environmental factors - fasting
Genetic - Gilbert’s
Factors that induce p450s (alcohol, meds) will increase NAPQI production

Question 18

How is acetaminophen toxicity treated?

Answer 18

N-acetyl cysteine to help make glutathione to push NAPQI to mecapturic acid instead of the toxic adduct

Question 19

What is the histologic hallmark of acetaminophen toxicity?
How does it differ from ischemic and viral injuries?
How does it differ from acute fatty liver of pregnancy?

Answer 19

centrilobular necrosis (same as ischemic injury)

Viral has massive hepatic necrosis but no centrilobar demarcation

Acute fatty liver of pregnancy has microvesicular fat

Question 20

What is the requisite clinical finding for the diagnosis of fulminant hepatic failure?

Answer 20

hepatic encephalopathy in less than 8 weeks from the onset of symptoms

Question 21

A patient comes in with disturbances of consciousness, impaired intellectual fuction and asterixis. You ask them to sign their name and they are unable to do so. What is it likely they have?

Answer 21

hepatic encephalopathy

Question 22

What is the first laboratory finding for the diagnosis of acute liver failure?

Answer 22

Coagulopathy (prolonged PT and INR)
It is the first lab detected in acetaminophen OD because of the centrilobular bleeding pattern.

clotting factors have short half lives so they quickly demonstrate liver injury

Question 23

What is the differential diagnosis of acute liver failure?

Answer 23

1. decompensation of underlying chronic liver disease (alcohol)
2. non-hepatic causes of encephalopathy:
   - metabolic (uremia, hypoxia, hyponatremia, hyper/hypoglycemia, sepsis, delerium tremens)
   - ischemia, toxins, vit, def, endocrine probs

Question 24

What differentiates non-hepatic causes of encephalopathy from hepatic?

Answer 24

The ammonia will not be elevated (except in rena and a genetic disorderl) and the there will be a lack of coagulopathy

Question 25

What is the treatment for fulminant liver failure?

Answer 25

1. autologous replacement
2. allogenic replacement (transplant)

While waiting for new liver to grow, you must

• give IV glucose to maintain levels
• head elevation, hyperventilation,diuretics to lower pressure
• avoid HYPER capnia, glycemia, thermia and HYPOnatremia because they increase pressure