Liver Toxicity

Question 1

Above what value (roughly) is a high bilirubin?

Answer 1

1 mg/dL

Question 2

Above what value (roughly) is a high AST/ALT?

Answer 2

40 U/L

Question 3

Above what value (roughly) is a high Alkaline Phosphatase?

Answer 3

140 U/L

Question 4

DILI classification

Answer 4

Any of the following:
- Total bili >2.5 mg/dL and any elevation in ALT, AST or ALP
- ALT >5x upper normal limit
- AST >5x ULN
- ALP >2x ULN
- INR >1.5 with elevated AST, ALT, or ALP

Question 5

Types of DILI

Answer 5

Hepatocellular (high AST/ALT)
Cholestatic (high ALP)
Mixed

Question 6

R value formula

Answer 6

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

Question 7

R for hepatocellular DILI

Answer 7

at least 5

Question 8

R for cholestatic DILI

Answer 8

at most 2

Question 9

R for mixed DILI

Answer 9

2-5

Question 10

Amox/clav

Answer 10

1 on DILIN list

• Known to cause cholestatic jaundice
• Can cause hepatocellular injury
• HLA-DRB1*15 gene
• Symptoms 2-45 days after ingestion

Question 11

Top 2 drug classes likely to cause DILI

Answer 11

1. Antimicrobials*
2. Herbal and dietary supplements

Question 12

Top 5 drugs likely to cause DILI

Answer 12

1. Amox/clav
2. Isoniazid
3. Nitrofurantoin
4. Bactrim
5. Minocycline

Question 13

Which NSAID causes DILI

Answer 13

Diclofenac

Question 14

Which antimicrobials have fast DILI onset

Answer 14

Ciprofloxacin, Levofloxacin

Question 15

Dietary supplements

Answer 15

Not FDA regulated - contain lots of garbage
- Hydroxycut
- NO-XPLODE

Question 16

When can you consider rechallenging a DILI-causing agent?

Answer 16

If the patient ONLY had cholestatic injury

Question 17

APAP hepatotoxicity

Answer 17

AST > 1000 U/L
- N/V
- Malaise
- Pallor
- Diaphoresis

Question 18

APAP toxicity management

Answer 18

1. Activated charcoal (if presenting <4 hours)
2. NAC***
3. Supportive care

Question 19

When to start NAC after hour 24?

Answer 19

• If AST is elevated
• If APAP level detectable (also with unknown late ingestion)

Question 20

When to start NAC at hours 4-24?

Answer 20

Indicated by nomogram
- AST >1000 U/L

Question 21

What should you do <4h?

Answer 21

Consider activated charcoal
Wait until hour 4 to check APAP levels before starting NAC

Question 22

When is IV NAC preferred over PO?

Answer 22

• Established liver disease
• Other organs affected
• Shorter hospital stay desired
• Pregnancy
• Unable to tolerate PO

Question 23

What is the biggest problem with IV NAC?

Answer 23

Anaphylactoid reactions (look like anaphylaxis) up to 17% of patients
- Treat with Benadryl/steroids, resume

Question 24

When to continue NAC past protocol?

Answer 24

• Ongoing liver failure (high PT/INR, encephalopathy)
• Detectable APAP or ongoing hepatocyte damage (high AST)

Question 25

PO NAC pearls

Answer 25

• Solution should be diluted to 5% and covered with a soft drink (it smells bad)
• If vomited, repeat <1 hour
• Longer protocol (72h)