Acute Liver Failure Flashcards
Define acute liver failure.
An acute liver injury with encephalopathy and deranged coagulation (INR > 1.5) in a patient with a previously normal liver.
What is the most common cause of acute liver failure in the UK?
Paracetamol overdose - cause of 50% of cases in the UK.
Give examples of viral causes of acute liver failure.
- HAV, HBC, HEV
- Cytomegalovirus
- HSV
- EBV
Give examples of drugs which can cause acute liver failure.
- Paracetamol (acetaminophen)
- ABx
- Ampicillin-clavulanate
- Ciprofloxacin
- Doxycycline
- Erythromycin
- Antidepressants
- Amitriptyline
- Nortriptyline
- Antiepileptics
- Phenytoin
- Valproate
- NSAIDs
Give examples of toxins which can cause acute liver failure.
- Cyanobacteria toxin
- Yellow phosphorus
- Bacillus cereus toxin
What are the causes of acute hepatic failure in pregnancy?
- Acute fatty liver of pregnancy (AFLP)
- HELLP (haemolysis, elevated liver enzymes, low platelets)
Give examples of the vascular causes of acute liver failure.
- Ischaemic hepatitis
- Budd-Chiari syndrome
- Portal vein thrombosis
Give examples of the metabolic causes of acute liver failure.
- α1-antitrypsin deficiency
- Fructose intolerance
- Reye syndrome
- Wilson’s disease
Give examples of malignancies which can cause acute liver failure.
- Primary (usually HCC, rarely cholangiocarcinoma)
- Secondary (extensive hepatic metastases or infiltration)
Describe the examination findings seen in acute liver failure.
- Jaundiced patient with a small liver and signs of hepatic encephalopathy.
- The mental state varies from slight drowsiness, confusion and disorientation (grades I and II) to unresponsive coma (grade IV) with convulsions.
- Fetor hepaticus is common. Ascites and splenomegaly are rare.
- Fever, vomiting, hypotension and hypoglycaemia occur.
- Neurological examination shows spasticity and hyper-reflexia. Plantar responses remain flexor until late.
- Cerebral oedema develops in 80% of patients with AHF. Far less common in subacute hepatic failure. Its consequences of intracranial hypertension and brain herniation account for ~25% of the causes of death.
- Other complications include bacterial and fungal infections, GI bleeding, respiratory arrest, kidney injury (hepatorenal syndrome and acute tubular necrosis) and pancreatitis.
Describe the abnormalities in blood tests seen in acute liver failure.
- Hyperbilirubinaemia
- High serum aminotransferases (ALT and AST)
- Low levels of coagulation factors, including prothrombin and favtor V
What factors can indcate prognosis in acute liver failure?
- Aminotransferases are not useful indicators of the course of the disease, as they tend to fall along with the albumin with progressive liver damage.
- EEG can be helpful in grading the encephalopathy (prognosis).
- USS will define liver size and may indicate underlying liver pathology.
- In mild cases (grades I and II encephalopathy with drowsiness and confusion), 2/3 of the patients will survive. The outcome of severe cases (grades III and IV encephalopathy with stupor or deep coma) is related to the aetiology.
- In special units, 70% of patients with paracetamol overdosage and grade IV coma survive, as do 30-40% of patients with HAV or HBV hepatitis.
What are the poor prognostic variables which indicate a need to transplant the liver?
Describe the mechanism of hepatotoxicity in paracetamol overdose.
- In therapeutic doses, paracetamol is conjugated with glucuronide and sulphate.
- A small amount of paracetamol is metabolised by mixed-function oxidase enzymes to form a highly reactive toxic compound (N-acetyl-p-benzoquinoneimine, NAPQI), which is then immediately conjugated with glutathione and subsequently excreted as cysteine and mercapturic conjugates.
- In overdose, large amounts of paracetamol are metabolised by oxidation because of saturation of the sulphate conjugation pathway. Liver glutathione stores become depleted so that the liver is unable to deactivate NAPQI.
- Paracetamol-induced kidney injury probably results from a mechanism similar to that responsible for hepatotoxicity.
- Acetylcysteine replenishes glutathione stores.
Outline the principles of treatment of paracetamol overdose.
- Acetylcysteine is an effective protective agent, provided it is administered within 8-10 hours of ingestion of the overdose.
- It acts by replenishing cellular glutathione stores, though it may also repair oxidation damage caused by NAPQI.
- The treatment regimen is shown in the picture.
- Patients with concentrations above a ‘treatment line’ starting at 100mg/L 4 hours after ingestion should be given treatment with acetylcysteine.
- The treatment lines are uncertain if the patient presents 15 hours or more after ingestion, or has taken a modified-release preparation of paracetamol.
- Patients who ingest multiple overdoses or take repeated therapeutic excess are at greater risk of liver damage, and decisions to treat are generally based on the dose ingested.
- In the UK, treatment with acetylcysteine is given if more than 75mg/kg has been ingested in 24 hours.
