Drug Induced Liver Disease

Question 1

Liver Function Tests (LFTs)

Answer 1

Aminotransferases (AST &ALT)
Alkaline Phosphatase (ALP)

Question 2

Synthetic Function Tests

Answer 2

Albumin
PT/INR

Question 3

LFTs normal levels

Answer 3

AST: 5-40 U/L

ALT: 5-40 U/L

ALP: 30-140 U/L

Question 4

Bilirubin normal values

Answer 4

Total bili < 1.2 mg/dL
usually around 1

Question 5

DILI definition

Answer 5

Total bili > 2.5mg/dL + any elevation in ALT, AST, or ALP

ALT > 5x ULN
AST > 5x ULN
ALP > 2x ULN
INR > 1.5 w/ elevated AST, ALT, or ALP

Question 6

R value

Answer 6

R= [ALT/40] / [ALP/140]

Question 7

Hepatocellular DILI

Answer 7

AST + ALT elevation
R >/= 5

Question 8

Cholestatic DILI

Answer 8

ALP elevation
R </= 2

Question 9

Mixed DILI

Answer 9

R: 2-5

Question 10

Amoxicillin-Clavulanate related DILI

Answer 10

sx onset 2-45 days after admin

most common antibiotic cause

Management:
- supportive care

Question 11

Herbal & Dietary Supplements

Answer 11

16.1% of cases

Common: hydroxycut, NO-XPLODE
- bodybuilding supps

Question 12

APAP DILI Mechanism

Answer 12

Liver can’t keep up

Glutathione (enzyme) is depleted -> build up of toxic NAPQI

Question 13

APAP DILI Clinical Presentation

Answer 13

N/V
malaise
pallor
diaphoresis
liver injury not seen until 24-36 hrs post injection (inc in AST>1000 IU/L)

max toxicity at 72-96 hrs
- AST & ALT > 10,000
- changes in INR, bili, glucose, lactate, phosphate, pH, renal failure

• death 3-5 days post OD
• those who survive make full recovery

Question 14

APAP DILI Management

Answer 14

if 1-2hrs post ingestion: activated charcoal

NAC

Supportive
- IV fluids
- management of N/V
- correction of hypoglycemia
- Vitamin K/FFP

Question 15

NAC

Answer 15

Glutathione substitute

near complete efficacy when given w/in 8 hrs of OD

check APAP level at 4-24 hrs -> use Rumack-Matthew Nomogram to determine if NAC is indicated

IV vs PO
- equal efficacy
- IV NAC results in higher [systemic] and may be preferred when other organs are affected

Question 16

PO NAC

Answer 16

Dosing: 72hr protocol
- 140mg/kg LD
- 70mg/kg Q4H up to total of 1330 mg/kg
- dilute solution to 5% with a soft drink and covered to help with the smell
- repeat dose if vomited within 1 hr of ingested

ADE:
- bad taste
- N/V (pre-treat with antiemetics)

Change to IV if liver failure develops

Question 17

IV NAC

Answer 17

Dosing: 20 hr protocol
- 150 mg/kg LD over 60 min
- 50 mg/kg over 4 hrs
- 100 mg/kg over next 16 hrs
- total dose 300 mg/kg

ADE:
- anaphylactoid reaction (usually minor, pats can almost always restart without recurrence)

Preferred in liver failure, pregnancy, and inability to tolerate PO

Question 18

When to continue NAC past protocol

Answer 18

ongoing liver failure
- elevated PT/INR
- encephalopathy

Detectable APAP or ongoing hepatocyte damage
- APAP > 10 mcg/mL
- AST > ULN and not decreasing
- AST > 1000 U/L