Lecture 1 - Drug Induced Liver Disease

Question 1

Direct Bilirubin is….

Answer 1

conjugated bilirubin

Question 2

Indirect Bilirubin is…

Answer 2

free unconjugated

Question 3

Markers of Liver injury

Answer 3

ALT
AST
ALP
GGT
GDH
LDH

Question 4

Markers of hepatocellular function

Answer 4

Bilirubin
Albumin
PT

Question 5

Risk factors for DILI

Answer 5

Adult > children
Women > men
Racial differences (W>B)
Comorbidites

** Highest risk of liver injury within 1st 90 days of med exposure **

Question 6

Asymptomatic Signs & Symptoms

Answer 6

1. Minor elevations in liver enzymes

2. Transient injury

Question 7

Symptomatic Signs & Symptoms

Answer 7

1. Elevations in liver enzymes & bilirubin

2. Jaundice

Question 8

Acute liver failure Signs & Symptoms

Answer 8

1. Symptomatic + Signs of encephalopathy or coagulopathy

** maybe considered life-treating and require liver transplant**

Question 9

Chronic Liver Disease Signs & Symptoms

Answer 9

1. Cirrhosis

2. Hepatic decompensation

Question 10

5 Steps of DILI

Answer 10

1. Is pt presenting w/ clinical features consistent with liver injury
2. What is the pattern/type of DILI based on clinical markers
3. What is the severity of the injury
4. What are the potential drug and/or non-drug causes of liver injury
5. What literature exists regarding the cause of injury due to this med

Question 11

Liver injury is defined as..

Answer 11

1. increase in ALT > 3 X ULN
or
2. ALP > 2X ULN
or 
3. total bilirubin > 2 X ULN and any ALT or ALP elevation

Question 12

ULN =

Answer 12

Upper limit of normal

Question 13

Hepatocellular pattern/type of injury

Answer 13

ALT > 3X ULN

Ratio >5

Question 14

Cholestatic pattern/type of injury

Answer 14

ALP > 2X ULN

Ratio < 2

Question 15

Mixed pattern/type of injury

Answer 15

ALT > 3X ULN
ALP > 2X ULN

Ratio 2 - 5

Question 16

Ratio Calculation

Answer 16

(ALT/ALT baseline or ULN) / ( ALP/ALP baseline or ULN)

Question 17

Severity of Injury Nonspecific signs/symptoms

Answer 17

Fatigue & Malase
Jaundice
Abdominal pain
Fever and Chills

Question 18

Hepatocellular symptoms

Answer 18

Nausea + Vomiting

Anorexia

Question 19

Cholestatic Symptoms

Answer 19

Pale Stools
Tea-colored dark urine
Pruritus

Question 20

Mixed symptoms

Answer 20

Nause + vomiting
Pale stools
Dark urine

Question 21

Hy’s Law

Answer 21

Applies to hepatocellular injury only

Jaundice (total bilirubin > 2 X ULN) + elevation in transaminase ( ALT or AST > 3X ULN)

Mortality can be as high as 14% w/ these features

Question 22

Meds that met Hy’s Law

Answer 22

Bromfenac
troglitazone
ximelagatran
dilevalol

Question 23

Coagulopathy assesment

Answer 23

INR
Albumin or pre-albumin
Transport proteins for bilirubin excretion

Question 24

Encephalopathy assessment

Answer 24

Bilirubin

Ammonia

Question 25

What goes into Child-Pugh Score

Answer 25

``` Ascites (round belly full of fluid) Bilirubin Albumin INR Encephalopathy ```

Question 26

Grade A Child-Pugh

Answer 26

5-6 | 1/2 yr survival = 100,85%

Question 27

Grade B Child-Pugh

Answer 27

7-9 | 1/2 yr survival = 80/60%

Question 28

Grade C Child-Pugh

Answer 28

10-15 | 1/2 yr survival 45,35%

Question 29

If Direct < Indirect Bilirubin then that means that....

Answer 29

can conjugate your bilirubin

Question 30

Stuff related to Hepatocellular pattern

Answer 30

``` Alcohol Fatty liver Viruses - Hep, EBV, CMV Hepatic infarction or congesstion Autoimmune ```

Question 31

Stuff related to Cholestatic pattern

Answer 31

Gall stones Pregnancy Alcohol Primary sclerosing cholangitis

Question 32

Max acetaminophen for healthy people

Answer 32

3-4g, probs closer to 3g for older adults

Question 33

Max of 2g/day acetaminophen if...

Answer 33

Heavy alcohol use Malnutrition DI Advanced age

Question 34

When to hold Atorvastatin in potential DILI?

Answer 34

ALt > 10 X ULN or persistent over 5 X or associated w/ symptoms of liver injury

Question 35

Managing Statins in liver injury

Answer 35

Monitor liver enzymes

Question 36

Treatment Approach DILI

Answer 36

1. D/x suspected Drug 2. Admin antidotes if available 3. Consider Steroids if hypersensitivity reaction...prednisone 4. supportive care for N/V/ itching 5. Treat encephalopathy 6. follow serial enzyme test and consult hematologist 7. consider transplant for acute liver failure

Question 37

Antidote for Acetaminophen

Answer 37

N-acetylcysteine

Question 38

Antidote for valproic acid

Answer 38

Carnitine

Question 39

DILI prevention strategies

Answer 39

1. Dont ignore danger symptoms 2. Take careful history 3. pay attention to Hy's Law and prognosis 4. Report injury to MedWatch