Drug Induced Liver Diseases Flashcards
AMA is seen in what disease?
Primary biliary cirrhosis
LKM is seen in what disease?
Autoimmune hepatitis
pANCA is seen in what disease?
Primary sclerosing cholangitis
What is the most frequent cause of drug induced liver injury? What drug, specifically?
Abx
Augmentin
What are the labs like in drug induced liver injury?
Transaminitis, elevated alk phos, and cholestatic pattern of bili
What is intrinsic drug induced liver injury? How long does this last?
Results from drug or metabolite inducing direct hepatocellular damage
Occurs with short latency
Does rechallenge with the intrinsic drug induced liver disease result in recurrence? Idiosyncratic?
Intrinsic = No Idiosyncratic = yes
What is the idiosyncratic drug induced liver disease?
Occurs in a minority of people, with prolonged latency, with unexpected effects with
What is the most frequent reason for withdrawal of an approved FDA drug from the market?
Drug induced liver injury
What is Hy’s law? What are the three factors involved?
A pt will have a 10% mortality risk of DILD even if offending drug is discontinued, provided they:
- Serum ALT or AST x3 ULN
- total bili 2x ULN w/o alk phos elevation
- No other reason
What is the most common cause of acute liver failure and transplantation in the West?
DILI
True or false: DILI is a diagnosis of exclusion
True
What are the risk factors for DILI?
- age
- gender
- obesity
- drug/EtOH exposure
What drug are men more likely to have DILI?
Azathioprine
Why does obesity lead to susceptibility of DILI?
Increased p450s in obesity can increase metabolite concentration
What is the most important factor in drug induced liver disease?
Genetic factors
True or false: pts with cirrhosis are more susceptible to DILI
Unclear
What is the most common cause of DILI?
Acetaminophen
What is the max dose of acetaminophen that can be given in 24 hours?
4 g
What are the two pathways in which acetaminophen can be metabolized?
Glucuronide or
NAPQI via p450
What happens to the NAPQI produced with acetaminophen?
can cause necrosis via covalent bonding
or
GSH to mercapturic acid, to excretion in urine (normal)
What is the antidote for acetaminophen overdose?
N-Acetylcysteine (NAC)
Should acetaminophen be given to pts with cirrhosis? Why or why not?
Yes, as long as there is NOT active alcoholism, since this may exacerbate hepatorenal syndrome
What percent of acetaminophen overdoses resolve spontaneously?
65%
What is the level of ALT and AST at which the liver is at risk of severe necrosis?
100x
Over what level of bili is concerning for cholestasis, and mixed injury?
more than 3x
What is the timeframe of acute DILI?
less than 3 months
What is the formula used to calculate the DILI?
ALT / alk phos
Which is more common, acute or chronic DILI?
Acute
What are the ssx of chronic DILI? What can this lead to?
Mimic complete extrahepatic obstructive jaundice with arrested bile flow
May lead to cirrhosis
DILI can mimic what viral infection?
Mono (LAD, lymphocytosis)
What are the extrahepatic ssx of DILI?
Fever
Rash
Eosinophilia
What is the risk of statins causing DILI?
Low
What is the treatment for DILI?
Stop the drug
What is the antidote for Valproate?
L-Carnitine
What is the cutoff for immediately stopping a drug with elevated LFTs?
greater than 5x normal
What is cutoff of LFTs for repeating liver enzymes every 3 month? every month?
less than 3x normal then 3 months
3-5x normal, repeat every 1 month
Should you rechallenge pts with DILI?
No, unless that’s the only drug that will work for them, and they need it.
