Drug Induced Liver Disease

Question 1

What labs do you want to test in possible liver disease?

Answer 1

RUQ Ultra Sound
Liver Size
INR
AMA, ASMA, ANA, LKM,
Ceruloplasmin, A1AT
Ferritin, Iron, TIBC
Iron Sat
Liver Biopsy

Question 2

What is the #1 drug for Drug induced liver disease?

Answer 2

Augmentin (Amoxicillin-Clauvulanic Acid)

Question 3

What is Drug induced liver disease?

Answer 3

Hepatotoxicity caused by drugs used either in medical practice, theraputic, nutritional, or recreational purposes including Drugs of abuse.

Question 4

How is liver disease objectively measured?

Answer 4

Elevation in Bilirubin, Alk Phos, AST, ALT, or GGT

Question 5

What are the different categories of DILD?

Answer 5

Intrinsic and Idiosyncratic

Question 6

What is Intrinsic DILD

Answer 6

Drug or metaolite induced direct hepatocyte damage.
Predictable at high doses
Short latency
Would affect majority of population at high enough dose
Acetaminophen
Re-Challenge doesn’t lead to recurrence

Question 7

What is Idiosyncratic DILD?

Answer 7

Occurrs in a minority of suceptible people
Rxns have variable and prolonged latency
Unexpected based on pharmacological action of the drug
Less consistnent relationship to dose

Question 8

What is the most frequent reason for withdrawl of an approved FDA drug from the market?

Answer 8

Drug induced liver injury

Question 9

What is Hy’s Law?

Answer 9

10% mortality risk of DILD even if offending drug is discontinued if 3 criteria are met.

Question 10

What are the three criteria of Hy’s law?

Answer 10

Serum ALT or AST >3X ULN
Serum total Bili >2 X ULN without initial findings of cholestasis
No other reason explains the elevation of liver enzymes

Question 11

What is the most common cause of Acute liver failure and transplant in western countries?

Answer 11

DILD

Question 12

What are risk factors for DILD?

Answer 12

Age 
Gender
Obesity
Exposure to Drugs, EtOH
History of previous drug rxns

Question 13

What are the challenges of Diagnosing DILD?

Answer 13

No specific Biomarker
Most reactions are idiosyncratic and cannot be easily preicted
Provign a drug IS NOT involved is challenging

Question 14

How can risk of DILD due to Genetic Factors be assessed?

Answer 14

Test to see how active the enzyme is that breaks down the drug you want to give them. If low or absent, high risk of DILD!

Question 15

What disease drug combo puts you at a higher risk of DILD?

Answer 15

HIV + HCV combo with antiretroviral drugs increase risk of DILD

Also those with Chronic Hepatitis

Question 16

Waht is the leadign cause of acute liver failure in the US?

Answer 16

Acetaminophen

Question 17

What are the FDA guidelines for acetaminophen?

Answer 17

Combo with opioid for prescription strength pain relief
325mg/tab. 2 tabs every 4 hrs
4g max dose in 24 hrs (12 tabs)

Question 18

How can liver be overwhelmed in Acetaminophen

Answer 18

pure Acetamin. OD

Alcohol + Acet.

Question 19

What is the cure for acetaminophen OD?

Answer 19

Give Glutathione Transferase

Question 20

When is Acetaminophen safe in a person with liver disease?

Answer 20

Not active alcoholism
Not malnourished
No starvation present

Question 21

What constitutes Acute DILI?

Answer 21

Duration of manifestations last

Question 22

What can cause Acute DILI?

Answer 22

Overdose
Idiosyncratic drug rxn
Drug Hypersensitivity

Question 23

What is Acute Drug induced Cholestatic Injury?

Answer 23

Mimic complete extrahepatic obstructive jaundice with arrested bile flow.
Sepsis, TPN, and CHF and cause a cholestatic pattern of injury

Question 24

What is Pseudomononucleosis?

Answer 24

Drug induced Hepatitis that may resemble infectious mononucleosis
Acute HC injury with
-Lymphadenopaty
-Lymphocytosis
-atypical circulatory lymphocytes