The Liver - Acute/Fulminant Hepatic Failure

Question 1

What is Acute Liver Failure?

Answer 1

Rapid onset of hepatocellular dysfunction, leading to a variety of systemic complications.

Question 2

Give 4 causes of Acute Liver Failure.

Answer 2

1. Paracetamol Overdose.
2. Alcohol.
3. Viral Hepatitis (usually A/B).
4. Acute Fatty Liver of Pregnancy.

Question 3

Give 6 clinical features of Acute Liver Failure.

Answer 3

1. Jaundice.
2. Coagulopathy : Raised PT Time (Abnormal Bleeding).
3. Hypoalbuminaemia.
4. Hepatic Encephalopathy.
5. Renal Failure (Hepatorenal Syndrome).
6. Ascites.

Question 4

Acute vs. Chronic Liver Failure.

Answer 4

Acute : Onset of Symptoms is in less than 26 weeks in a patient with a previously healthy liver.
Chronic : Onset of liver failure on a background of Cirrhosis.

Question 5

Types of Acute Liver Failure (3).

Answer 5

1. Hyperacute : 7 Days or Less.
2. Acute : 8-21 Days.
3. Subacute : 4-26 Weeks.

Question 6

Why may Fulminant hepatic Failure have a high mortality rate?

Answer 6

If cerebral oedema is severe, raised ICP can develop.

Question 7

Investigations of Acute Liver Failure (5).

Answer 7

1. Clinical Examination.
2. Blood Tests.
3. Ascites : Peritoneal Tap MCS.
4. Abdominal US.
5. Doppler US - Budd-Chiari Syndrome.

Question 8

Commonest Complication of Acute Liver Failure.

Answer 8

Infection - Bacterial (80%); Fungal (30%) - due to reduced phagocyte action, complement levels and multiple invasive interventions.

Question 9

Other Complications of Acute Liver Failure (4).

Answer 9

1. Cerebral Oedema (+/- ICP).
2. Bleeding.
3. Hypoglycaemia.
4. Multiple Organ Failure.

Question 10

Management of Acute Liver Failure (4).

Answer 10

1. Treat Underlying Cause.
2. Monitor Observations.
3. Treat Encephalopathy, Coagulopathy, SBP, Renal Dysfunction.
4. Liver Transplantation.

Question 11

Treatment of Encephalopathy (2).

Answer 11

1. Lactulose - Nitrogenous Waste Loss through Bowels (reduce Encephalopathy).
2. IV Mannitol (reduce cerebral oedema).

Question 12

Treatment of Coagulopathy (2).

Answer 12

1. Vitamin K - help production of coagulation factors.

2. FFP (Fresh Frozen Plasma ) - if bleeding.

Question 13

Treatment of Spontaneous Bacterial Peritonitis.

Answer 13

Broad-Spectrum Antibiotics.

Question 14

Urgent Liver Transplantation in Acute Liver Failure (1C + 2B).

Answer 14

King's Hospital Criteria :
1. Paracetamol-Induced (A+B+C) :
1A. Arterial pH < 7.3 24 hours after ingestion OR PT > 100s.
1B. Creatinine > 300umol/L.
1C. Grade III/IV Encephalopathy.
2. Non-Paracetamol (A or 3Bs).
A. PT > 100s.
B. (i) Drug-Induced Liver Failure; (ii) Age<10 or Age > 40; (iii) 1 week from 1st Jaundice to Encephalopathy; (iv) PT > 50s; (v) Bilirubin > 300umol/L.

Question 15

Clinical Features of Hepatic Encephalopathy (5).

Answer 15

1. Confusion e.g. Altered GCS.
2. Asterixis : Liver Flap, Arrhythmic Negative Myoclonus (Frequency 3-5Hz).
3. Constitutional Apraxia : Inability to draw a 5 Pointed Star.
4. Triphasic Slow Waves on EEG.
5. Raised Ammonia Level.

Question 16

Theory : Pathophysiology of Hepatic Encephalopathy.

Answer 16

Excess absorption of ammonia and glutamine from bacterial breakdown of proteins in the gut.

Question 17

Grading of Hepatic Encephalopathy (4).

Answer 17

I : Irritability.
II : Confusion, Inappropriate Behaviour.
III : Incoherence, Restlessness.
IV : Coma.

Question 18

Precipitating Factors of Hepatic Encephalopathy (8).

Answer 18

1. Infection e.g. SBP.
2. GI Bleed.
3. Post-TIPSS.
4. Constipation.
5. Drugs : Sedatives, Diuretics.
6. Hypokalaemia.
7. Renal Failure.
8. Increased Dietary Protein.

Question 19

Management of Hepatic Encephalopathy (3).

Answer 19

1. Treat Underlying Cause.
2. NICE : 1st Line - Lactulose (promote excretion of ammonia and increase metabolism of ammonia by gut bacteria) + Rifaximin (modulate gut flora resulting in decreased ammonia production) for Secondary Prophylaxis.
3. Other Options : Embolisation of Portosystemic Shunts and Liver Transplant.

Question 20

Pathophysiology of Paracetamol Overdose (2).

Answer 20

1. Metabolism of Paracetamol results in build-up of toxic substance : NAPQI (N-Acetyl-p-Benzoquinone-Imine).
2. NAPQI is inactivated by Glutathione but in an overdose, Glutathione stores are rapidly depleted so NAPQI is left unmetabolised.

Question 21

Management of Paracetamol Overdose (6).

Answer 21

1. If ingested less than 1 hour ago + dose > 150 mg/kg : ACTIVATED CHARCOAL (reduce absorption of drug).
2. If staggered overdose or ingestion > 15 hours ago : Start N-ACETYLCYSTEINE immediately.
3. If ingestion < 4 hours ago : Wait 4 hours to take a level and treat with N-Actylcysteine based on the level.
4. If ingestion 4-15 hours ago: Take immediate level and treat based on level.
5. Decision to treat is based on a nomogram : paracetamol levels are above treatment line.
6. N-Acetylcysteine is associated with anaphylactoid (non-IgE mediated mast cell release) reactions - just stop infusion and restart at a lower rate.

Question 22

Risk Factors of Hepatotoxicity from Paracetamol Overdose (2).

Answer 22

1. Liver-Enzyme Inducers : Rifampicin, Phenytoin, Carbamazepine, St. John’s wort, Chronic Alcohol Excess.
2. Depletion of Glutathione : Anorexia, Malnutrition and HIV.