Flashcards in DILI Deck (18):
What is the annual incidence of DILI?
1-10 per 100,000 people exposed
accounts for up to 10% of adverse drug reactions
most common cause of acute liver failure in the US
What are the patterns of acute liver injury caused by DILI?
- confluent necrosis
steatosis (less common)
What are the common causes of cholestatic DILI?
What are the features of a cholestatic DILI?
Predominantly elevated ALP, GGT and bilirubin
Aminotransferases are only mildly elevated (less than 8-fold)
overall good prognosis
What are the features of hepatocellular DILI?
Predominantly riased aminotransferases - similar to acute viral hepatitis
Histology: acute hepatocellular necrosis, apoptosis
can affect single hepatosyts or groups
confluent necrosis can result in acute liver failure
zonal necrosis: characteristic of compunds with predictable, dose-dependent toxicity e.g. Paracetamol
Non-zonal necrosis: viral hepatitis like pattern. More common with compounds that cause non-dose related injury e.g. Phenytoin, Diclofenac
Which drugs cause a hepatocellular type of DILI?
What drugs cause a mixed pattern of DILI?
Which drugs cause steatosis?
Drugs that disrupt beta-oxidation of lipids and oxidative energy production e.g. Amiodarone
What features suggest DILI?
exposure to drug prior to liver injury
exclusion of underlying liver disease
improvement after cessation of the drug
there are no specific markers and histological can resemble autoimmune hepatitis
What are the features of chronic DILI?
Abnormal LFTs > 3-6 months
Chronic hepatocellular damage tends to occurs in chronic drug use and resolves once drug is stopped
May progress to cirrhosis or liver failure
chronic DILI is serologically and morphologically indistinguishable from type1 autoimmune hepatitis
- more common in females, raised auto-immune markers (ANA, anti-SM Abs)
What are the features of Flucloxacillin induced DILI?
idiosyncratic reaction - mechanism poorly understoof
HLA B5701 association
most recover within several months after stopping the drug
can develop into chronic liver disease
vanishing bile duct syndrome can occue - prolonged damage leads to loss of bile ducts and over ductopaenia -> liver failure
What types of drug reactions can cause DILI?
- reaction occurs in any individual at a sufficient dose, e.g. Paracetamol
- no dose-response relationship
- the adverse reaction cannot be predicted from a drug’s pharmacological profile or from pre-clinical toxicology tests
What is the typical pattern of LFTs in alcoholic liver disease?
AST > ALT, ratio 2-3
What are the histological changes possible with alcoholic liver disease?
steatosis -> cirrhosis
How long will it take alcoholic fatty liver disease to normalise upon cessation of alcohol?
How much does ongoing alcohol comsumption increase the risk of developing cirrhosis?
40g/day increases the risk of progression to cirrhosis by 30%
How should alcoholic liver disease be treated?
Severe alcoholic liver disease may benefit from treatment with short-term prednisolone or pentoxifylline (if corticosteroid therapy is contraindicated by infection or kidney failure)