Exam 2 - Drug-Induced Liver Injury (DILI)

Question 1

T/F: DILI is the most common cause of acute liver failure in the US.

Answer 1

TRUE

Question 2

What medication causes the most drug-induced acute liver failure in the US?

Answer 2

APAP

Question 3

What 2 things do hepatotoxic drugs lead to?

Answer 3

1) Hepatocyte necrosis or apoptosis

2) Subsequent cell death

Question 4

Name the host-dependent risk factors for Idiosyncratic DILI.

Answer 4

• Age
• Gender
• Race
• Alcohol consumption
• PG
• Comorbidities

Question 5

Name the drug-dependent risk factors for Idiosyncratic DILI.

Answer 5

• Lipophilicity (LogP>3) plus daily dose (>100 mg)
• Concomitant drugs
• Reactive metabolites
• Oxidative stress
• Mitochondrial hazards
• Hepatobiliary transport inhibition

Question 6

Name the 3 types of DILI.

Answer 6

1) Intrinsic (Direct)
2) Idiosyncratic
3) Indirect

Question 7

T/F: Intrinsic (Direct) DILI is not dose-related.

Answer 7

FALSE

-Intrinsic (Direct) DILI is dose-related

Question 8

What is the latency period of Intrinsic (Direct) DILI?

Answer 8

Short (hours to a few days)

Question 9

What is the latency period of Idiosyncratic DILI?

Answer 9

Variable (days to weeks)

Question 10

What is the latency period of Indirect DILI?

Answer 10

Typically delayed (weeks to months)

Question 11

Which type of DILI has the highest rate of occurrence?

Answer 11

Intrinsic (Direct) DILI

Question 12

What is the mechanism of Intrinsic (Direct) DILI?

Answer 12

Intrinsic hepatotoxicity

Question 13

What is the mechanism of Idiosyncratic DILI?

Answer 13

Metabolic or immune-mediated damage

Question 14

What is the mechanism of Indirect DILI?

Answer 14

Drug effect causes undesirable liver effects

Question 15

Name the laboratory tests available for DILI.

Answer 15

• Serum aminotransferases (AST/ALT)
• Alkaline phosphatase (ALP)
• Total bilirubin (TBL)
• Gamma-glutamyltransferase (GGT)
• Serum albumin
• Coagulation parameters (PT/INR)

Question 16

What are the two serum aminotransferase lab tests?

Answer 16

1) AST

2) ALT

Question 17

What is ALP?

Answer 17

The Alkaline phosphatase lab test

Question 18

What is GGT?

Answer 18

The Gamma-glutamyltransferase lab test

Question 19

Which two lab tests measure severity of DILI?

Answer 19

1) Serum albumin

2) Coagulation parameters (PT/INR)

Question 20

ALT ____ x upper limit of normal (ULN).

Answer 20

ALT >5 x upper limit of normal (ULN).

Question 21

ALP ____ x ULN.

Answer 21

ALP >2 x ULN.

Question 22

ALT ___ x ULN + TBL ___ x ULN.

Answer 22

ALT >3 x ULN + TBL >2 x ULN.

Question 23

How do you calculate the R-value?

Answer 23

R = (ALT/ULN)/(ALP/ULN)

Question 24

What does an R value of >5 equal?

Answer 24

Hepatocellular injury

Question 25

What does an R value of <2 equal?

Answer 25

Cholestatic injury

Question 26

What does an R value of >2 and <5 equal?

Answer 26

Mixed injury

Question 27

What are the three DILI injuries based on R values?

Answer 27

1) Hepatocellular 2) Cholestatic 3) Mixed

Question 28

T/F: DILI can be asymptomatic or mild in presentation.

Answer 28

TRUE

Question 29

What do s/s of DILI present like?

Answer 29

Acute hepatitis-like syndrome | -Nausea, fatigue, jaundice, abdominal discomfort

Question 30

In cholestatic cases, what may limit the QOL of the patient?

Answer 30

- Pruritus | - Asthenia

Question 31

What are the immunoallergic features of DILI?

Answer 31

- Fever - Rash - Arthraliga - Lymph node enlargement

Question 32

Name the common drugs that cause Intrinsic DILI (4).

Answer 32

DAAS - Divalproex sodium/valproic acid - Acetaminophen - Amiodarone - Statins

Question 33

Name the common drugs that cause Idiosyncratic DILI (12).

Answer 33

"A FIND MAPS AS" - Allopurinol - Amiodarone - Amoxicillin-clauvulanate - Diclofenac - Fenofibrate - Isoniazid - Ketoconazole - Minocycline - Nitrofurantoin - Phenytoin - Statins - Sulfonamides

Question 34

What is the drug of choice for Acetaminophen toxicity?

Answer 34

NAC (N-Acetylcysteine)