Patient professional reference
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 to 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 UK, 775 liver transplants a year were performed in the year April 2012 to April 2013. The number of transplants has been increasing in recent years.
- The annual incidence of acute liver failure in the Scottish population was 0.62 per 100,000 between 1992 and 2009. Paracetamol overdose was the largest causative factor.
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.
- Illicit drugs including ecstasy and cocaine.
- Reye's syndrome.
- Viral hepatitis.
- Adenovirus, Epstein-Barr virus, cytomegalovirus and viral haemorrhagic fevers
- Wilson's disease.
- Others - eg, alpha-1-antitrypsin deficiency, fructose intolerance, galactosaemia and tyrosinaemia.
- Acute fatty liver of pregnancy - see the separate article on Jaudice in Pregnancy.
- Ischaemia or veno-occlusive disease.
- Budd-Chiari syndrome.
- Autoimmune liver disease.
- Unknown cause - 15%.
Mental faculties may be so impaired that history from someone close may be required. There may be hallucinations. Haematemesis or melaena may indicate gastrointestinal bleeding.
- Date of onset of jaundice and encephalopathy.
- Alcohol use.
- Medication, including prescription medicines, illicit drugs and alternative 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.
- 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 article on Hepatic Encephalopathy.
- 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.
- FBC may 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 if there are massive ascites, obesity, or 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.
- Poisoning with drugs such as paracetamol or mushrooms may require specific interventions.
- Lactulose, often with neomycin, is given to reduce ammonia production.
- Protein restriction may not be as important as is traditionally taught.
- Mannitol may reduce raised intracranial pressure. Try to avoid sedatives, as they make assessment difficult. Intracranial pressure monitoring is sometimes required.
- Cerebral oedema often leads to brain herniation and death. A possible treatment that is being assessed is hypothermia.
- 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:
- The most important variables for predicting the need of transplantation in fulminant hepatic failure are the degree of encephalopathy, the patient's age and the underlying cause of liver failure.
- May be life-saving if a graft becomes available. Various artificial liver devices have been developed and they may bridge the gap until transplant or spontaneous recovery. These include a bio-artificial liver.
- 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.
- 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:
- 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.
- Two key factors involved in determining outcome are aetiology and coma grade on admission.
- Paracetamol overdose, hepatitis A, ischaemia and pregnancy 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.
Further reading and references
UK Transplant Statistics; NHS Blood and Transplant, August 2013
Bretherick AD, Craig DG, Masterton G, et al; Acute liver failure in Scotland between 1992 and 2009 incidence, aetiology and outcome. QJM. 2011 Nov
Chang CY, Schiano TD; Review article: drug hepatotoxicity. Aliment Pharmacol Ther. 2007 May 1525(10):1135-51.
Stickel F, Egerer G, Seitz HK; Hepatotoxicity of botanicals. Public Health Nutr. 2000 Jun3(2):113-24.
Hirschfield GM, Gibbs P, Griffiths WJ; Adult liver transplantation: what non-specialists need to know. BMJ. 2009 May 22338:b1670. doi: 10.1136/bmj.b1670.
Shawcross D, Jalan R; Dispelling myths in the treatment of hepatic encephalopathy. Lancet. 2005 Jan 29-Feb 4365(9457):431-3.
Jalan R, Rose C; Hypothermia in acute liver failure. Metab Brain Dis. 2004 Dec19(3-4):215-21.
Mannucci PM, Tripodi A; Liver disease, coagulopathies and transfusion therapy. Blood Transfus. 2013 Jan11(1):32-6. doi: 10.2450/2012.0151-12. Epub 2012 Sep 12.
Gotthardt D, Riediger C, Weiss KH, et al; Fulminant hepatic failure: etiology and indications for liver transplantation. Nephrol Dial Transplant. 2007 Sep22 Suppl 8:viii5-viii8.
Demetriou AA, Brown RS Jr, Busuttil RW, et al; Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg. 2004 May239(5):660-7
Scott TR, Kronsten VT, Hughes RD, et al; Pathophysiology of cerebral oedema in acute liver failure. World J Gastroenterol. 2013 Dec 2819(48):9240-9255.
Lee WM; Recent developments in acute liver failure. Best Pract Res Clin Gastroenterol. 2012 Feb26(1):3-16. doi: 10.1016/j.bpg.2012.01.014.
Du WB, Pan XP, Li LJ; Prognostic models for acute liver failure. Hepatobiliary Pancreat Dis Int. 2010 Apr9(2):122-8.
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