Liver failure

What is liver failure?

Hepatic failure occurs when the liver loses the ability to regenerate or repair, so that decompensation occurs. It is marked by:

• Hepatic encephalopathy (HE).

• Coagulopathy.

• Jaundice.

If this occurs rapidly in a patient with no previous liver disease it is termed acute liver failure. If the person has previously had liver disease it is termed acute on chronic liver failure.

How common is liver failure? (Epidemiology)

In the Western world, acute liver failure is estimated to affect fewer than 6.5 people per million population per year.¹ Globally, the incidence varies and viral infection accounts for the majority of cases of liver failure.

Causes of liver failure (aetiology)

There are many causes of hepatic failure and the following represent just a few.

Toxins

• Chronic alcohol abuse.

• Paracetamol poisoning. This can occur at a lower level than expected in chronic alcohol users.

• Drug toxicity associated with co-amoxiclav, ciprofloxacin, doxycycline, erythromycin, isoniazid, nitrofurantoin, halothane, statins, cyclophosphamide, methotrexate, disulfiram, flutamide, gold and propylthiouracil. NB: the list is NOT comprehensive.

• Poisoning by various substances, including mushrooms or chemicals containing carbon tetrachloride and other organic solvents and phosphorus.

• Herbal preparations, plants and plant products.²

• Illicit drugs, including ecstasy and cocaine.

• Reye's syndrome.

Infections

• Viral hepatitis.

• Adenovirus, Epstein-Barr virus, cytomegalovirus and viral haemorrhagic fevers.

Neoplastic

• Hepatocellular carcinoma or metastatic carcinoma.

Metabolic

• Wilson's disease.

• Others - eg, alpha-1-antitrypsin deficiency, fructose intolerance, galactosaemia and tyrosinaemia.

Pregnancy-related

• Acute fatty liver of pregnancy or pre-eclampsia - see the separate Jaundice in Pregnancy article.

Vascular

• Ischaemia or veno-occlusive disease.

• Budd-Chiari syndrome.

Others

• Autoimmune liver disease.

• Unknown cause.

History

Cognition may be so impaired that history from someone close may be required. There may be hallucinations. Haematemesis or melaena may indicate gastrointestinal bleeding.

Ask about:

• Date of onset of jaundice and encephalopathy.

• Symptoms and signs focusing on gastrointestinal history, such as nausea, vomiting, haematemesis, melaena. A systemic enquiry may raise the possibility of undiagnosed chronic disease or occult malignancy.

• Alcohol use.

• Medication, including prescription medicines, illicit drugs and alternative/complementary medicines.

• Family history of liver disease (Wilson's disease or haemochromatosis).

• Exposure risk factors for viral hepatitis (travel, transfusions, sexual contacts, occupation, body piercing).

• Toxin ingestion (mushrooms, organic solvents, phosphorus contained in fireworks).

• Past medical history eg, previous cancer and treatment received.

Examination

The following may be present.

• Respiratory distress.

• Jaundice.

• Reduced effective circulating volume due to fluid redistribution.

• Hyperdynamic circulation with multiple organ failure may mimic septic shock.

• Abdominal distension and abdominal masses, including:
  

  • Possible massive ascites and anasarca due to fluid redistribution and hypoalbuminaemia.

  • A dehydrated patient may not show much ascites.

  • Hepatomegaly and splenomegaly but not invariably. Patients with chronic liver disease may have liver atrophy.

• Cerebral oedema with increased intracranial pressure (ICP), may produce papilloedema, hypertension, and bradycardia.

• Liver palms are red and an hepatic flap, also called asterixis, may be present:
  

  • Hyperextend the fingers and wrist, gently pushing back and a slow clonic movement is the liver flap.

• Particular care should be given to identifying hepatic encephalopathy: see the separate Hepatic Encephalopathy article.

Differential diagnosis

• Structural lesions or space-occupying lesions in the brain.

• Cerebral infection - bacterial or viral.

• Drug or alcohol intoxication.

• Delirium tremens or Wernicke's encephalopathy.

• Metabolic upset such as hypoglycaemia, ketoacidosis, electrolyte imbalance, hypoxia, hypercapnia.

Diagnosing liver failure (investigations)

Haematology and Biochemistry

• FBC may show thrombocytopenia and anaemia due to chronic disease or blood loss.

• Coagulation screen: INR will be raised.

• Liver, lactate and renal blood markers. Transaminases are very markedly raised.

• Bilirubin is raised. This may not be the case in hyperacute failure. There may be elevated lactate, hypoxia and raised creatinine, especially if there is hepatorenal syndrome or acute kidney injury. Hyponatraemia can occur.

• Glucose can be very low and must be monitored.

• Ammonia levels are high. Lactate is high. This should preferably be estimated on arterial blood.

• Urine and blood toxicology, including paracetamol level.

• Tests to identify specific precipitating conditions such as free copper for Wilson's disease or autoimmune disease.

Microbiology and Virology

• Blood cultures. Urine and sputum cultures should also be performed due to infection susceptibility.

• Viral serology may indicate the infection that precipitated the hepatic failure.

Imaging

• Ultrasound, CT or MRI scanning to demonstrate the hepatic anatomy and identify cirrhosis or malignancy.

• Imaging of the head may demonstrate cerebral oedema.

• Liver biopsy may be considered in line with recommendations to reduce the bleeding risk.³

Management of liver failure

Early recognition of the diagnosis and transfer to a specialist unit are required. The complications of liver failure are wide ranging and life-threatening. Hourly vital signs and invasive fluid assessment monitoring are recommended along with regular senior review. The possibility of liver transplantation should be considered at an early stage with consideration of prognostic indicators.^{4 5}

Management focuses on treating the cause of liver failure, supporting physiological recovery and reducing the risk of complications. Management can be split into the areas below.³

• Managing condition-specific factors: Poisoning with drugs such as paracetamol or mushrooms may require specific interventions.

• Cardiovascular management: fluid status and blood pressure often requires invasive monitoring to attain euvolaemic status.

• Respiratory management: intubation and ventilation may be required for airway protection. Acute respiratory distress syndrome may be present.

• Gastrointestinal management: stress ulcer prophylaxis is often recommended but should be weighed against the risk this poses (increased risk of ventilator associated pneumonia and Clostridium difficile infection) Nutrition requirements may necessitate enteral feeding. Monitor for pancreatitis development.

• Renal management: Acute kidney injury is present in 40-80% of patients with acute liver failure. ³ Renal replacement therapy may be required.

• Biochemical disturbance. Gross biochemical disturbance is commonly seen in patient biochemistry. Raised ammonia and hypoglycaemia are two of the most common abnormalities.

• Neurological management: Regular neurological assessment is the minimum requirement to monitor for HE.

• Liver transplantation may be life-saving if a graft becomes available. Artificial liver devices have been developed and they may bridge the gap until transplant or spontaneous recovery.⁶

Complications of liver failure

• Infection is a great problem. Spontaneous peritonitis is common, as is infection of access lines. Sepsis should be vigilantly watched for.

• Cerebral oedema may be associated with intracranial hypertension and death.⁷ The measures to reduce this are beyond the scope of this article.

• Disordered coagulation test results. Oesophageal varices may require attention. Haemorrhage from various sources may be a problem but some patients have normal clotting ability despite abnormal results, due to rebalancing within the coagulation system.

The major complications that cause death, even after transplantation, are sepsis, cerebral oedema, acute kidney injury, and respiratory failure.

Prognosis

Acute liver failure remains unpredictable with high morbidity and mortality. Early and accurate diagnosis, management and prognostic assessment of patients with acute liver failure are essential as prognosis depends on the cause of hepatic failure. Severe liver failure and subacute failure are poor prognostic indicators. Research is ongoing into other prognostic factors.