Lecture 1 - Drug Induced Liver Disease Flashcards
Direct Bilirubin is….
conjugated bilirubin
Indirect Bilirubin is…
free unconjugated
Markers of Liver injury
ALT AST ALP GGT GDH LDH
Markers of hepatocellular function
Bilirubin
Albumin
PT
Risk factors for DILI
Adult > children
Women > men
Racial differences (W>B)
Comorbidites
** Highest risk of liver injury within 1st 90 days of med exposure **
Asymptomatic Signs & Symptoms
- Minor elevations in liver enzymes
2. Transient injury
Symptomatic Signs & Symptoms
- Elevations in liver enzymes & bilirubin
2. Jaundice
Acute liver failure Signs & Symptoms
- Symptomatic + Signs of encephalopathy or coagulopathy
** maybe considered life-treating and require liver transplant**
Chronic Liver Disease Signs & Symptoms
- Cirrhosis
2. Hepatic decompensation
5 Steps of DILI
- Is pt presenting w/ clinical features consistent with liver injury
- What is the pattern/type of DILI based on clinical markers
- What is the severity of the injury
- What are the potential drug and/or non-drug causes of liver injury
- What literature exists regarding the cause of injury due to this med
Liver injury is defined as..
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
ULN =
Upper limit of normal
Hepatocellular pattern/type of injury
ALT > 3X ULN
Ratio >5
Cholestatic pattern/type of injury
ALP > 2X ULN
Ratio < 2
Mixed pattern/type of injury
ALT > 3X ULN
ALP > 2X ULN
Ratio 2 - 5
Ratio Calculation
(ALT/ALT baseline or ULN) / ( ALP/ALP baseline or ULN)
Severity of Injury Nonspecific signs/symptoms
Fatigue & Malase
Jaundice
Abdominal pain
Fever and Chills
Hepatocellular symptoms
Nausea + Vomiting
Anorexia
Cholestatic Symptoms
Pale Stools
Tea-colored dark urine
Pruritus
Mixed symptoms
Nause + vomiting
Pale stools
Dark urine
Hy’s Law
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
Meds that met Hy’s Law
Bromfenac
troglitazone
ximelagatran
dilevalol
Coagulopathy assesment
INR
Albumin or pre-albumin
Transport proteins for bilirubin excretion
Encephalopathy assessment
Bilirubin
Ammonia
What goes into Child-Pugh Score
Ascites (round belly full of fluid) Bilirubin Albumin INR Encephalopathy
Grade A Child-Pugh
5-6
1/2 yr survival = 100,85%
Grade B Child-Pugh
7-9
1/2 yr survival = 80/60%
Grade C Child-Pugh
10-15
1/2 yr survival 45,35%
If Direct < Indirect Bilirubin then that means that….
can conjugate your bilirubin
Stuff related to Hepatocellular pattern
Alcohol Fatty liver Viruses - Hep, EBV, CMV Hepatic infarction or congesstion Autoimmune
Stuff related to Cholestatic pattern
Gall stones
Pregnancy
Alcohol
Primary sclerosing cholangitis
Max acetaminophen for healthy people
3-4g, probs closer to 3g for older adults
Max of 2g/day acetaminophen if…
Heavy alcohol use
Malnutrition
DI
Advanced age
When to hold Atorvastatin in potential DILI?
ALt > 10 X ULN or persistent over 5 X or associated w/ symptoms of liver injury
Managing Statins in liver injury
Monitor liver enzymes
Treatment Approach DILI
- D/x suspected Drug
- Admin antidotes if available
- Consider Steroids if hypersensitivity reaction…prednisone
- supportive care for N/V/ itching
- Treat encephalopathy
- follow serial enzyme test and consult hematologist
- consider transplant for acute liver failure
Antidote for Acetaminophen
N-acetylcysteine
Antidote for valproic acid
Carnitine
DILI prevention strategies
- Dont ignore danger symptoms
- Take careful history
- pay attention to Hy’s Law and prognosis
- Report injury to MedWatch
