Acute and Chronic Liver Failure

Question 1

What is acute liver failure?

Answer 1

Rapid deterioration in liver function (INR >1.5) and encephalopathy in setting of previously normal liver.

Question 2

Aetiology of acute liver failure?

Answer 2

• Drugs (esp paracetamol)
• Hep B / A
• Ischaemic (circulatory shock; acute severe heart failure)
• Idiosyncratic acute drug reaction
• Idiopathic

Question 3

Mx acute liver failure?

Answer 3

• Correct hypoglycemia
• Monitor GCS
• Prevent GI bleed w/ PPI
• Monitor for infection, MODS
• Consider Bx before INR too high
• Exclude chronic liver disease
• Transplant

Question 4

What are the major functions of the liver?

Answer 4

• Synthesis of clotting factors
• Glucose homeostasis; glycogen storage
• Albumin synthesis
• Bilirubin conjugation / clearance
• NH3 metabolism (urea cycle)
• Drug metabolism and clearance
• Immune: dealing w/ gut derived bacteria and bacterial products

Question 5

T1/2 alb and significance of this?

Answer 5

Albumin half life =20d therefore can remain normal in acute liver injury

Question 6

Features of clotting profile (INR v APTT) in liver disease?

Answer 6

INR affected more by liver disease than APTT

Question 7

What is the liver enzyme pattern of hepatocellular injury / necrosis?

Answer 7

• Elevation of ALT/AST

- Very high ALT in acute viral hepatitis, acute drug toxicity, ischaemia

Question 8

What is the liver enzyme pattern of intra- or extra-hepatic cholestasis?

Answer 8

• Elevation of ALP and GGT
• High ALP/GGT w/ minor elevation of transaminases typical of biliary obstruction, liver infiltration, cholestatic reactions to drugs

Question 9

What are the common causes of acute hepatitis?

Answer 9

1. Acute viral hepatitis
2. Drug related
3. Ischaemic hepatitis
4. Autoimmune
5. Acute Budd Chiari
6. Wilson’s disease
7. Idiopathic

Question 10

What are the criteria for transfer to liver transplant unit?

Answer 10

• INR >1.5 and rising
• Any encephalopathy
• Poor prognosis
• Oliguria or creatinine > 200 umol/L
• Acidosis with pH

Question 11

How can prolonged fasting interact with potential paracetamol toxicity?

Answer 11

Prolonged starvation an increase susceptibility to paracetamol poisoning by depleting hepatic glutathione stores.

Question 12

Prognosis of acute liver failure?

Answer 12

• Survival >70%
• Increased survival probably reflects availability of transplant as rescue therapy
• highly dependent on aetiology and rate of progression

Question 13

How is liver transplant listing determined?

Answer 13

Using Kings College Criteria (KCC); different for ALF non-paracetamol v paracetamol.
-Identifies pts w/ poor prognosis who need transplantation.

Question 14

What is the role of Bx in acute liver failure?

Answer 14

• Quantify extent of liver injury
• Establish aetiology of liver injury
• Guide Rx

Question 15

What are Kings Criteria for liver transplantation in FHF due to paracetamol od?

Answer 15

• pH 100s
• Cr >300umol/L
• Grade III or IV encephalopathy

Question 16

What is the toxic dose of paracetamol at 24, 48 and >48h?

Answer 16

24: 200mg/kg or 10g (whichever is less).
48: 150mg/kg or 6g/day whichever is less
>48: 100mg/kg or 4g/day (whichever is less)

Question 17

Explain paracetamol metabolism and OD.

Answer 17

Usually paracetamol conjugated with glucuronide for excretion in bile. 5% forms NAPQI for conjugation with glutathione. Excess doses overwhelm glucuronide and glutathione systems, with unconjugated NAPQI producing hepatoxicity.

Question 18

How does N-acetylcysteine act to prevent hepatoxicity?

Answer 18

Acts as glutathione donor reducing production of NAPQI. 100% effective if administered within 8h.

Question 19

What are the causes of chronic liver disease?

Answer 19

Rule of 3s:

• EtOH, HBV, HCV
• Genetic: Wilson’s, Haeochromatosis, A1AT deficiency
• AI: PBC, PSC, AI hepatitis
• Other: NASH, Budd Chiari, drugs