DILI

Question 1

What is the most common cause of acute liver failure in the developed world?

Answer 1

Drug- induced liver injury

Question 2

Amoxicillin toxicity usually happens when mixing it with what drug?

Answer 2

When combined with clavulonic acid

Question 3

Which class of medications most commonly causes drug-induced liver injury?

Answer 3

Acetaminophen (45-50%) Antimicrobials (~45% of cases), followed by herbal and dietary supplements (~16%).

Question 4

How common are idiosyncratic drug-induced liver reactions?

Answer 4

Rare, occurring in fewer than 1 in 10,000 exposed patients.

Question 5

What major types of drug-induced hepatotoxicity exist?

Answer 5

Direct (intrinsic) toxicity

Idiosyncratic toxicity.

Question 6

Why is the diagnosis of drug-induced liver injury difficult?

Answer 6

Because clinical, laboratory, and histologic findings are often indistinguishable from other liver diseases.

Question 7

What hepatic metabolic system is responsible for most drug metabolism that may generate toxic intermediates?

Answer 7

Cytochrome P450 enzyme system (phase I metabolism).

Question 8

What detoxification mechanism neutralizes NAPQI metabolites in the liver?

Answer 8

Glutathione conjugation via glutathione S-transferase.

Question 9

What occurs if glutathione stores are depleted during drug metabolism?

Answer 9

Toxic metabolites accumulate and cause hepatocyte injury.

Question 10

Name cellular mechanisms through which drugs may cause hepatocyte injury.

Answer 10

Free radical formation

Membrane lipid peroxidation

Covalent protein binding

Apoptosis activation

Mitochondrial dysfunction

Impaired bile salt export.

Question 11

What transporter dysfunction can contribute to drug-induced cholestasis?

Answer 11

Inhibition of bile canalicular pumps causing accumulation of toxic bile acids.

Question 12

What genetic factor often determines susceptibility to idiosyncratic drug hepatotoxicity?

Answer 12

Polymorphisms in drug-metabolizing enzyme

Question 13

What immunologic mechanism may contribute to some cases of drug-induced liver injury?

Answer 13

Drug metabolites bind host proteins forming neoantigens that trigger immune responses.

Question 14

What defines intrinsic (direct) drug-induced hepatotoxicity?

Answer 14

Predictable, dose-dependent toxicity with short latency.

Question 15

What defines idiosyncratic drug-induced hepatotoxicity?

Answer 15

Unpredictable, not dose-dependent, and occurs rarely.

Question 16

What clinical features may suggest a hypersensitivity-mediated idiosyncratic reaction?

Answer 16

Rash, fever, arthralgia, eosinophilia, leukocytosis.

Question 17

What phenomenon describes mild transaminase elevation that resolves despite continued drug use?

Answer 17

Drug adaptation.

Question 18

Which commonly used drugs may show adaptation with mild transient transaminase elevation?

Answer 18

Isoniazid, valproate, phenytoin, and statins.

Question 19

Idosyncratic hepatotoxicity characteristics

Answer 19

Unpredictable
Not dose-dependant
May involve extrahepatic features (fever, rash, eosinophilia)
Occurs only in suceptible individuals
Most common cause: amoxi/clav

Question 20

Hepatocellular patern of hepatic injury

Answer 20

Elevated transaminases

Usually due to acetaminophen

Question 21

What are the two major biochemical patterns of drug-induced liver injury?

Answer 21

Hepatocellular

Cholestatic (or mixed).

Question 22

Who usually presents hepatocellular damage?

Answer 22

Younger patients

Question 23

Intrinsic hepatotoxicity characteristics

Answer 23

Predectable and dose-dependent
Short latent periods (hours to days)
Prototypic agent: acetaminophen

Question 24

Cholestatic pattern

Answer 24

Pruritus, jaundice, and elevated alkaline phophatate and GGT

Usually due to amoxi/clav

Question 25

Who usually presents cholestasis?

Answer 25

Older patients (hyperbillirubinemia)

Question 26

Cause of metabolic liver necrosis

Answer 26

NAPQI

Question 27

Therapeutic safe dose of paracetamol

Answer 27

4 g/day

Question 28

Which drugs classically cause a mixed hepatocellular–cholestatic pattern of drug-induced liver injury?

Answer 28

Statins and sulfonamides

Question 29

Toxic dose of paracetamol

Answer 29

10-15 g

Question 30

Fatal dose of paracetamol

Answer 30

25 g/day

Question 31

Which enzyme generates the toxic acetaminophen metabolite NAPQI?

Answer 31

CYP2E1.

Question 32

What antidote is used for acetaminophen overdose?

Answer 32

N-acetylcysteine (NAC).

Question 33

What is the mechanism of action of N-acetylcysteine in acetaminophen toxicity?

Answer 33

Replenishes hepatic glutathione stores to detoxify NAPQI.

Question 34

Early phase clinical presentation and timing of acetaminophen intoxication

Answer 34

4-12 hours: nausea, vomiting, diahrrea and shock

Question 35

Latent phase clinical presentation and timing of acetaminophen intoxication

Answer 35

24-48 hours. initial symptoms may abate while hepatic injury becomes biochemically aparent

Question 36

Potentiation of paracetamol toxicity

Answer 36

Chronic alcohol use → induces CYP450 Glutathione depletion → alcohol consumption and starvation decrease hepatic gluthatione levels Therapeutic Misadventures → toxcitity in malnourished and alcoholic can be only 2 g/day Drug interactions→ phenobarbital and isoniazid might potatiate injury

Question 37

Managment of paracetamol toxicity

Answer 37

NAC (N-acetylsysteine) needs to be given within 8 hours of ingestion

Question 38

What early symptoms are common in drug-induced liver injury?

Answer 38

Anorexia, fatigue, and right upper quadrant discomfort.

Question 39

What laboratory pattern suggests hepatocellular injury?

Answer 39

Elevated aminotransferases (AST/ALT)

Question 40

What confirms suspicion of drug-induced liver injury after stopping the drug?

Answer 40

Improvement of liver tests after drug withdrawal.

Question 41

What is Hy’s law used for in drug-induced liver injury?

Answer 41

Predicting severe liver injury risk and predicts high risk of liver faliure and mortality.

Question 42

What criteria define Hy’s law?

Answer 42

ALT >3× upper limit of normal Total bilirubin >2× upper limit No evidence of cholestasis.

Question 43

Which antibiotic combination is a frequent cause of cholestatic DILI?

Answer 43

Amoxicillin-clavulanate.

Question 44

Which component of amoxicillin-clavulanate is responsible for hepatotoxicity?

Answer 44

Clavulanic acid.

Question 45

What pattern of liver injury is typical for amoxicillin-clavulanate?

Answer 45

Cholestatic or mixed hepatocellular-cholestatic injury.

Question 46

What is the primary treatment for most cases of drug-induced liver injury?

Answer 46

Immediate discontinuation of the offending drug.

Question 47

How quickly do liver enzymes typically normalize after drug withdrawal?

Answer 47

Within 1–2 weeks in most self-limited cases.