EtOH and Drug induced liver diseases

Question 1

Pathogenesis of EtOH liver disease

Answer 1

Chronic EtOH misuse –> inflammation, apoptosis, fibrosis and reduced regeneration of hepatocytes

90-95% –> steatosis
10-20% –> fibrosis
8-20% –> cirrhosis
3-10% –> HCC

Question 2

Risk factors for EtOH liver disease

Answer 2

Female
Binge drinking
Viral hepatitis
HIV
Obesity
Smoking

Genetics - PNPLA3

Question 3

Histological changes of EtOH

Answer 3

Mallory hyaline = EtOH

Hepatitis = neutrophils, fatty changes, necrosis of hepatocytes

Question 4

Management of acute EtOH hepatitis

Answer 4

Low risk
= MDF <32or MELD<18
= Nutritional intervention

High risk
= MDF >32 or MELD >18
= Nutritional intervention
= Prednisone
= NAC

Question 5

Acute changes to ALT in drug induced hepatitis

Answer 5

ALT raised +++ Then quickly falls with removal of drug

Bilirubin peaks high and later then falls to normal

Question 6

Paracetamol metabolism

Answer 6

90% metabolised into inactive sulphate and glucuronide conjugates that are excreted in the urine

10% = cytochrome P450 –> formation of NAPQI

NAPQI –> bound to intracellular glutathione –> elimination in urine as mercapturic adducts

Question 7

Treatment of paracetamol OD

Answer 7

NAC infusion until paracetamol levels normalise or INR and ALT/AST are normal

Question 8

Criteria of liver transplant in paracetamol OD

Answer 8

pH <7.3

OR

INR >6.5 and creatinine >340 and encephalopathy

Question 9

Common causes of drug induced cholestasis

Answer 9

Chlorpromazine
Anti-androgens
OCP
Ketoconazole
Flucloxacillin
Amoxy/clav
Diclox
NSAIDS
Psychotropics