Acute Liver Failure

Question 1

What is acute liver failure?

Answer 1

It is defined as jaundice, coagulopathy (INR > 1.5) and hepatic encephalopathy

Question 2

What are the causes of acute liver failure?

Answer 2

Paracetamol overdose,
Alcohol,
Viral hepatitis (usually A or B),
Acute liver failure of pregnancy

Question 3

What are the clinical features of hepatic encephalopathy?

Answer 3

Confusion, asterix, apraxia, slow waves on EEG, raised amonium level

Question 4

What are the clinical features of acute liver failure?

Answer 4

Jaundice,
Coagulopathy (raised prothrombin time/INR >1.5)
Hypoalbuminaemia,
Hepatic encephalopathy,
Renal failure (hepatorenal syndrome)

Question 5

What tests look at the synthetic function of the liver?

Answer 5

Albumin and prothrombin levels

Question 6

What is the pathophysiology of hepatic encephalopathy?

Answer 6

In liver failure ammonia accumulated in the circulation. This is a small molecule which can cross the BBB. Once in cerebral circulation astrocytes detoxify it into glutamine. Excess glutamine disrupts osmotic balance and astrocytes swell causing cerebral oedema.

Question 7

What are the four grades of hepatic encephalopathy?

Answer 7

Grade 1 - Irritability,
Grade 2 - Confusion and inappropriate behaviour
Grade 3 - Incoherent and restless.
Grade 4 - Coma

Question 8

What are some precipitating factors for hepatic encephalopathy?

Answer 8

Infections (SBP),
GI bleed,
Post TIPS ,
Constipation,
Drugs (sedatives, diuretics),
Hypokalaemia,
renal failure

Question 9

What is the management of hepatic encephalopathy?

Answer 9

Treat underlying cause.
Give lactulose (increases gut excretion of ammonia and increases metabolism of ammonia)
Secondary prophylaxis - addition of rifaximin (modulates gut flora causing reduced ammonia)

Question 10

What are the investigations for acute liver failure?

Answer 10

LFTs,
Prothrombin time/INR,
FBC,
U&Es,
Paracetamol level,
ABG,
Viral hepatitis serology,
Autoimmune hepatitis markers,
Pregnancy test,
CXR,
Abdominal ultrasound

Question 11

Which patient’s are at risk of a paracetamol overdose?

Answer 11

Patients on liver enzyme inducing drugs (rifampicin, phenytoin, carbamazepine, St John’s wort).
Malnurished patients (anorexia nervosa) or patient’s who haven’t eaten in days.

Question 12

What is the treatment for a paracetamol overdose IF they present within 1 hour?

Answer 12

Activated charcoal as this reduces the absorption of the drug

Question 13

What is another treatment for paracetamol overdose and its indications?

Answer 13

Acetylcysteine. Given if:
Paracetamol concentration is above treatment line of 100mg/L at 4 hours at 15mg/L at 15 hours.
Staggered overdose or doubt of time paracetamol ingested.
Patients presenting in 8-24 hr who ingested more than 150mg/kg.
Patients who present >24h but clearly jaundiced, hepatic tenderness or raised ALT.

Question 14

How is acetylcysteine given?

Answer 14

Infusion over 1 hour (not 15mins) - this is to reduce the number of adverse effects. Can cause anaphylaxis - in this case stop transfusion and restart at lower dose.

Question 15

What is the criteria for liver transplant with paracetamol liver failure?

Answer 15

ABG - pH < 7.3 24 hours after ingestion.
Or all of following: PT > 100 seconds, creatinine > 300 and grade III or IV encephalopathy.

Question 16

What is a staggered overdose?

Answer 16

If not all tablets were taking within 1 hour.

Question 17

When should acetylcysteine be stopped?

Answer 17

Once there is improvement of hepatic function

Question 18

What is the pathophysiology of a paracetamol overdose?

Answer 18

Excess buildup of NAPQI (normally inactivated by glutathione). Results in liver and kidney damage.

Question 19

What is Wilson’s disease?

Answer 19

Defect in ATP7B gene which results in excessive copper deposition in the tissues.

Question 20

What are the clinical features of Wilson’s disease?

Answer 20

Liver deposition - Hepatitis, cirrhosis.
Neurological - Basal ganglia degeneration, (speech, behavioral and psychiatric problems), asterixis, chorea, dementia, parkinsonism.
Kayser- Fleischer rings
Renal tubular acidosis,
Haemolysis
Blue nails,
osteopenia

Question 21

What are theinvestigations for Wilson’s disease?

Answer 21

Slit lamp examination for Kayser Fleischer rings.
Reduced caeruloplasmin (protein which carried copper in the blood),
GOLD STANDARD - Liver biopsy
Reduced total serum copper (as most copper in plasma in bound)
Increased 24hr urinary copper excretion.
Confrim diagnosis with analysis of ATP7B gene

Question 22

What is the treatment for Wilson’s disease?

Answer 22

Copper chelation with penicillamine or trientine