Drug induced liver injury Flashcards
What are the three forms of liver injury
Hepatocellular injury
cholestasis
Mixed
What might hepatocellular injury result from
Drug or its metabolites
What do paracetamol and methotrexate cause
direct hepatocellular toxicity
What are the mechanisms of drug-induced liver injury
Disruption of the cell membrane
Production of immune targets by covalent binding of the drug to cell proteins
Inhibition of cellular pathways of drug metabolism
Abnormal bile flow due to disruption of subcellular actin filaments or interruption of transport pumps
Programmed cell death (apoptosis) mediated by tumour necrosis factor and Fas pathways
Inhibition of mitochondrial function causing accumulation of reactive oxygen species, lipid peroxidation, fat accumulation and cell death
What is the most important factor for susceptibility to DILI
Genetic variability
What are the clinical features of DILI
Acute hepatitis
Cholestasis
A mixed condition resembling acute viral hepatitis
What is the prognosis dependent on in DILI
The presence of jaundice
What is hepatocellular injury defined as
A rise in ALT of more than 2 fold or
ALT/AP ratio >5
What is acute cholestatic injury defined as
An increase in the ALP >2 x ULN or an ALT/ALP
What are the main causative agents in DILI
Antibiotics
NSAIDs
Antiseizure medication
Herbal preparations
When might a liver biopsy be useful
Where there is a suspicion of an underlying liver disease
What is the management for DILI
No effective treatment other than stopping the implicated drug and providing supportive care
What is the leading cause of acute liver failure
Paracetamol overdose
What dose of paracetamol results in serious or fatal adverse effects
150mg/kg
What are the clinical features of a paracetamol overdose
Asymptomatic for the first 24hours after infestion
Hepatic necrosis begins after 24h resulting in RUW pain, jaundice and elevated transaminases
