Drug Induced Liver Injury (DILI) and Acute Liver Failure (ALF) Flashcards
Risk factors of DILI and ALF
- Advanced age
- Alcohol use
- Genetic predisposition
- Pregnancy
Definition of Acute Liver Failure (ALF)
- INR > 1.5
- Hepatic encephalopathy
- <26 weeks Illness without apparent chronic liver disease
- Examples: viral hepatitis, autoimmune, liver disease, shock, or hypoperfusion
When judging likely hood of DILI
1) Onset- 5days to 3months or 24 to 72hrs
2) Time of recovery- usually see improvements with in days of stopping therapy , full improvement within 2 to 3 months
3) Clinical pattern of injury- look at the pattern of liver enzymes
Hepatocellular injury
- ALT >2x ULN
- ALT:ALK ratio >5
- Isoniazid, or methyldopa
Cholestatic injury
- ALK> 2x ULN
- ALT:ALK ratio <2
- Augmentin, erythromycin
Mixed
- ALT and ALK elevated
- ALT> 8x ULN
- Phenytoin, enalapril
Other Causes of liver injury
- Hepatitis
- Alcohol use
- Weight gain
- Autoimmune disease
- History of cardiac failure
- ALL drug use
Antituberculosis Drugs
- Well know hepatotoxic effects
- Drugs: Isoniazid, pyrazinamide,rifampicin
Acetaminophen
- Can cause liver damage
- However it is the preferred analgesic in patients with liver disease or cirrhosis
- Safer than NSAIDs or aspirin
- Toxicity is associated with a metabolite of Tylenol
Management of DILI
1) Identify offending drug and discontinue, if ALF hold/discontinue all non-essential medications
2) Administer antidote if available
3) Offer supportive care
- Steroids are helpful if autoimmune but NOT for general DILI management
- Give tenofovir for HBV
- UDSA for cholestatic injury (helps reduce itching)
Furosemide
- Electrolyte abnormalities
- Hepatorenal syndrome
ACEi
- Increased RAS effect
- Hypotension
NSAIDs
- Renal failure
- Increased bleed risk
- Hepatorenal syndrome
- Fatal GI bleeds
- Anemia
Aminoglycosides
- Renal Failure
- Hepatorenal syndrome
The most common drugs which cause DILI…
-ARE NOT PREDOMINATLY METABOLIZED by the liver
