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This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Liver Failure article more useful, or one of our other health articles.

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

  • Fulminant hepatic failure (FHF) occurs when the failure takes place within eight weeks of the onset of the underlying illness.
  • Late-onset hepatic failure (also called subacute FHF) occurs when there has been a gap of 8-26 weeks. The difference may not immediately be obvious, as the underlying disease may have been present for a long time but undiagnosed.
  • Chronic decompensated hepatic failure occurs when the latent period is over six months.
  • In the Western world, acute liver failure is estimated to affect fewer than 6.5 people per million population per year[1]. Globally, viral infection accounts for the majority of cases of liver failure; however, paracetamol overdose is the leading cause in the UK.
  • In the UK, 990 liver transplants were performed between 1st April 2017 and 31st March 2018. The number of transplants has been increasing in recent years and is set to rise further after the change in law to an 'opt-out system' in 2020[2].

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


  • 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[3].
  • Illicit drugs, including ecstasy and cocaine.
  • Reye's syndrome.







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.
  • 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.
  • Mental state shows drowsiness and possibly confusion.
  • Jaundice.
  • 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.
  • 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.
  • Hepatic encephalopathy: see the separate Hepatic Encephalopathy article.


  • FBC is likely to show an iron-deficiency anaemia picture (seen in about 75% of patients with chronic liver disease)[4].
  • FBC may also show thrombocytopenia.
  • INR will be raised. Although these are sensitive tests they may indicate other causes, such as vitamin K deficiency or disseminated intravascular coagulation.
  • Transaminases are very markedly raised but alkaline phosphatase may be slightly high or normal.
  • Bilirubin is raised.
  • Pseudocholinesterase is low.
  • Ammonia levels are high. This should preferably be estimated on arterial blood.
  • Glucose can be dangerously low and must be monitored.
  • There may be elevated lactate, hypoxia and raised creatinine, especially if there is hepatorenal syndrome or acute kidney injury.
  • Blood cultures. They are very susceptible to infection.
  • Viral serology may indicate the infection that precipitated the hepatic failure.
  • Tests for specific conditions include free copper for Wilson's disease and paracetamol levels in case of poisoning.


  • Doppler ultrasound may establish whether or not the hepatic vein is patent (Budd-Chiari syndrome) as well as looking for primary or secondary carcinoma and checking for ascites.
  • CT or MRI scanning may demonstrate the hepatic anatomy and can exclude other pathology, particularly in patients with massive ascites, or obesity, or where transplantation is considered. Avoid contrast in case it damages the kidneys.
  • Imaging of the head may demonstrate cerebral oedema.
  • EEG may help define level of encephalopathy.
  • Liver biopsy should be avoided with compromised coagulation, although a transjugular approach is sometimes used. 

Early recognition of the diagnosis and transfer to a specialist unit are required. The possibility of liver transplantation should be considered at an early stage with consideration of prognostic indicators[5, 6].

  • Poisoning with drugs such as paracetamol or mushrooms may require specific interventions.
  • Lactulose, often with neomycin, is given to reduce ammonia production.
  • Protein restriction is no longer universally recommended[7].
  • Mannitol may reduce raised intracranial pressure. Try to avoid sedatives, as they make assessment difficult. Intracranial pressure monitoring is sometimes required.
  • Cerebral oedema may lead to brain herniation and death. Therapeutic hypothermia may be used when standard medical treatments are not successful[8].
  • Acute kidney injury may require haemodialysis or continuous arteriovenous haemofiltration, as the former can drop blood pressure to a dangerous level.
  • Fresh-frozen plasma, platelet concentrates, antifibrinolytic drugs, prothrombin complex concentrates and recombinant activated factor VII are often used to treat or prevent abnormal bleeding .
  • Monitor glucose and other biochemical parameters. Large amounts of IV glucose may be required.
  • 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[9]
  • Infection is a great problem. Spontaneous peritonitis is common, as is infection of one of the access lines. Opportunistic infection and pneumonia may occur.
  • Cerebral oedema may be associated with intracranial hypertension and death[10].
  • Haemorrhage can be a considerable problem. Oesophageal varices may require attention. If large transfusion requirements exceed apparent blood loss consider retroperitoneal haemorrhage.
  • The major complications that cause death, even after transplantation, are bleeding, sepsis, cerebral oedema, acute kidney injury, and respiratory failure.

Prognosis depends on the cause of the hepatic failure, and 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.

  • Paracetamol overdose, hepatitis A, ischaemia and pregnancy-related causes are all associated with at least 60% short-term survival without transplantation.
  • Idiosyncratic drug-induced liver injury, hepatitis B, autoimmune hepatitis and indeterminate causes are associated with about 30% spontaneous survival. Presenting with early coma grade allows for a much more favourable outcome prediction across all aetiologies.
  • Patients with hyperacute liver failure (defined as development of encephalopathy within seven days of onset of illness) generally have a good prognosis with medical management, whereas those with subacute liver failure (defined as development of encephalopathy within 5-26 weeks of onset of illness) have a poor prognosis without liver transplant[11].

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Further reading and references

  1. Donnelly MC, Davidson JS, Martin K, et al; Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study). Aliment Pharmacol Ther. 2017 Mar45(6):833-843. doi: 10.1111/apt.13943. Epub 2017 Jan 18.

  2. UK Transplant Statistics; NHS Blood and Transplant

  3. Douros A, Bronder E, Andersohn F, et al; Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study. Int J Mol Sci. 2016 Jan 1517(1). pii: ijms17010114. doi: 10.3390/ijms17010114.

  4. Iron deficiency anemia in chronic liver disease: causes, diagnosis and treatment

  5. Mendizabal M, Silva MO; Liver transplantation in acute liver failure: A challenging scenario. World J Gastroenterol. 2016 Jan 2822(4):1523-31. doi: 10.3748/wjg.v22.i4.1523.

  6. Putignano A, Gustot T; New concepts in acute-on-chronic liver failure: Implications for liver transplantation. Liver Transpl. 2017 Feb23(2):234-243. doi: 10.1002/lt.24654. Epub 2017 Jan 6.

  7. Perumpail BJ, Li AA, Cholankeril G, et al; Optimizing the Nutritional Support of Adult Patients in the Setting of Cirrhosis. Nutrients. 2017 Oct 139(10). pii: nu9101114. doi: 10.3390/nu9101114.

  8. Castillo L, Bugedo G, Rovegno M; Therapeutic hypothermia as a bridge to transplantation in patients with fulminant hepatic failure. Rev Bras Ter Intensiva. 2015 Jan-Mar27(1):72-6. doi: 10.5935/0103-507X.20150012. Epub 2015 Mar 1.

  9. Lee KC, Stadlbauer V, Jalan R; Extracorporeal liver support devices for listed patients. Liver Transpl. 2016 Jun22(6):839-48. doi: 10.1002/lt.24396.

  10. Paschoal FM Junior, Nogueira RC, Oliveira ML, et al; Cerebral hemodynamic and metabolic changes in fulminant hepatic failure. Arq Neuropsiquiatr. 2017 Jul75(7):470-476. doi: 10.1590/0004-282X20170076.

  11. Singh T, Gupta N, Alkhouri N, et al; A guide to managing acute liver failure. Cleve Clin J Med. 2016 Jun83(6):453-62. doi: 10.3949/ccjm.83a.15101.