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Flashcards in DILI Deck (18):
1

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

2

What are the patterns of acute liver injury caused by DILI?

cholestasis
hepatocellular
- confluent necrosis
mixed
steatosis (less common)

3

What are the common causes of cholestatic DILI?

Augmentin
Carbamazepine
Erythromycin
Ketoconazole
Rifampicin
Flucloxacillin

4

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

5

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

6

Which drugs cause a hepatocellular type of DILI?

Paracetamol
Phenytoin
Diclofenac

7

What drugs cause a mixed pattern of DILI?

Phenyotin
Fluoroquinolones

8

Which drugs cause steatosis?

Drugs that disrupt beta-oxidation of lipids and oxidative energy production e.g. Amiodarone

9

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

10

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)

11

What are the features of Flucloxacillin induced DILI?

cholestatic pattern
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

12

What types of drug reactions can cause DILI?

Predictable
- reaction occurs in any individual at a sufficient dose, e.g. Paracetamol

Idiosyncratic
- no dose-response relationship
- the adverse reaction cannot be predicted from a drug’s pharmacological profile or from pre-clinical toxicology tests
e.g. Flucloxacillin

13

What is the typical pattern of LFTs in alcoholic liver disease?

AST > ALT, ratio 2-3

14

What are the histological changes possible with alcoholic liver disease?

steatosis -> cirrhosis

15

How long will it take alcoholic fatty liver disease to normalise upon cessation of alcohol?

4-6 weeks

16

How much does ongoing alcohol comsumption increase the risk of developing cirrhosis?

40g/day increases the risk of progression to cirrhosis by 30%

17

How should alcoholic liver disease be treated?

Cessation support
Severe alcoholic liver disease may benefit from treatment with short-term prednisolone or pentoxifylline (if corticosteroid therapy is contraindicated by infection or kidney failure)

18

How is alcoholic liver disease severity quantified?

Maddrey discriminant function (MDF)
MDF = 4.6 (prothrombin time [s] – control prothrombin time [s]) + total bilirubin (mg/dL)

Patients with MDF scores of 32 or greater (indicating severe alcoholic hepatitis) have short-term mortality risks as high as 50%

MELD score of 18+ has similar prognostic implications