Management of acute liver failure in intensive care

Learning objectives.

By reading this article, you should be able to:

• •Recall the common aetiologies of acute liver failure (ALF) both in the UK and globally.
• •Describe the pathophysiology of ALF leading to multiorgan failure.
• •Formulate a clear management plan for patients with ALF.

Key points.

• •Acute liver failure (ALF) is a rare but severe life-threatening emergency that warrants a multidisciplinary approach and early referral to a liver transplantation centre.
• •Liver transplantation has significantly improved outcomes from ALF.
• •Transplant-free survival, particularly for ALF caused by paracetamol overdose, has also improved as a result of better organ system support measures.
• •The leading causes of ALF globally are hepatitis B and E, whereas in the UK paracetamol-induced liver injury is the predominant aetiology.
• •The incidence of intracranial hypertension (ICH) has been continuously decreasing over the years and it is no longer the leading cause of mortality in patients with ALF.

Acute liver failure (ALF) is a highly specific liver condition characterised by a rapidly progressive life-threatening illness. It is defined as the presence of coagulopathy (international normalised ratio [INR] >1.5) and hepatic encephalopathy (HE) in a patient with an otherwise healthy liver.¹ Coagulopathy alone, in the absence of HE, is termed acute liver injury (ALI), which carries a much better prognosis.

This is a rare illness with a rate of less than 10 cases per million person years, and in severe cases is associated with multi-organ failure and high mortality.² The overall incidence is declining worldwide because of better vaccination programmes for hepatitis B and fewer drug-related cases.³ Emergency liver transplantation (LT) remains the definitive treatment for those progressing to severe disease.

This is in contrast to acute-on-chronic liver failure (ACLF), characterised by an acute decline in liver function in patients with pre-existing chronic liver disease (CLD). This can progress to extrahepatic organ failure and is associated with high short-term mortality. Acute-on-chronic liver failure should be differentiated from ALF. Exceptions to this rule is de novo presentation of liver failure in patients with autoimmune hepatitis (AIH), Budd–Chiari syndrome, or acute Wilson's disease, in which the underlying chronic pathology would have previously gone undiagnosed and acute presentation mimics the ALF phenotype.

Aetiology

The aetiology of ALF varies across the world, with viral infections being the common causes in the developing world and drug-induced liver injury (DILI) in developed settings. Paracetamol toxicity accounts for 50–70% of all cases of DILI, but since the UK restriction on purchasing there has been a 43% reduction in deaths.^3,4 In developing countries hepatitis B and E are responsible for the majority of cases of ALF, with a predominance of hepatitis E in the Indian subcontinent.³ Acute liver failure is also seen with hepatitis A, particularly in some Asian and Mediterranean countries.⁵ The syndrome of ALF can be subclassified according to the time interval between the onset of jaundice and the development of HE; hyperacute ALF (HALF; HE within 7 days of developing jaundice), ALF (HE within 8 and 28 days of developing jaundice), and subacute ALF (SALF; HE within 28 days and 12 weeks of developing jaundice).⁶ This classification can sometimes provide clues as to the potential underlying aetiology and prognosis (Fig. 1). However, in up to 20% of the cases, despite rigorous investigation, the cause of the ALF remains unidentified and is referred to as indeterminate or cryptogenic.³

Fig 1.

Subclassification of acute liver failure (ALF) to aid in identifying underlying aetiology and possible prognostication.^1,6 Adapted from Willars CWJ, Liver failure, Oh's Intensive Care Medicine Manual, 2013; 501–19. Reproduced with permission from Elsevier. HELLP, haemolysis, elevated liver enzyme, and low platelet levels.

Prognosis

The outcomes from ALF have improved significantly over the past few decades in developed countries. This has been driven by parallel improvements in the understanding of disease pathophysiology, early referrals to specialist centres equipped with a transplantation facility, better organ system support in ICU, and the availability of emergency LT, leading to improved outcomes for those managed medically or receiving an LT.⁷ Mode of death has also changed over time with intracranial hypertension (ICH) replaced by sepsis and multiple organ failure as the leading cause of death.⁷ The patient's age (older patients do less well), disease aetiology (pregnancy-related ALF has excellent transplant-free survival, whereas acute Wilson's disease has very poor prognosis without transplantation) and the speed of disease progression (Fig. 1) can provide prognostic determinants. HALF is associated with the development of severe coagulopathy, higher grades of encephalopathy, and greater incidence of ICH, and multiorgan dysfunction. However, offset is also rapid with excellent rates of transplant-free recovery. Conversely, SALF develops over a much longer period and is often associated with only modest increases in serum transaminases and mild coagulopathy. These patients can present with splenomegaly, ascites, and shrinking liver volumes, mimicking cirrhosis, which can make the diagnosis challenging.¹ Once HE develops in these patients, there is little chance of spontaneous recovery and the prognosis is very poor without transplantation.³

Pathophysiology

Acute liver failure is characterised by direct hepatocyte damage, necrotic or apoptotic cell damage, and the development of an immune response that is mediated through activated monocytes, macrophages, dendritic, cells and natural killer T cells. The cells express Toll-like receptors (TLRs) which recognise both pathogen-associated molecular patterns (PAMPs) from infectious causes, and damage-associated molecular patterns (DAMPs) from non-infectious insults. This results in a strong inflammatory response, both locally within the liver and systemically. Systemic inflammation contributes to the development of extrahepatic manifestations and multiple organ dysfunction syndrome (MODS).⁸ This is similar to the systemic inflammatory response syndrome (SIRS) seen in sepsis, with an initial proinflammatory response causing MODS, followed by an anti-inflammatory response characterised by immune paresis that predisposes to new infections.

Hepatic encephalopathy, a hallmark feature of ALF, is characterised by altered cerebral blood flow and dysregulated cerebral autoregulation. The exact pathological basis of subsequent progression to cerebral oedema and ICH is not completely understood and is likely to involve a complex interplay between systemic inflammation, circulating neurotoxins (ammonia in particular), and osmolar derangements such as hyponatraemia, the end result being astrocyte swelling, brain oedema, and ICH.^3,7,8

Management

Diagnosis

Patients present with a range of symptoms including non-specific features of nausea, vomiting, lethargy, abdominal pain, and feeling generally unwell. The diagnosis may also be delayed if the primary presenting features are those of confusion and agitation, particularly in the hyperacute cases related to paracetamol poisoning where, in some instances, there may be little jaundice with only mild increase of serum bilirubin, and in cases with subacute disease, which can be mistaken for CLD.² A clinical history should focus on features of mental alterations (HE), the presence and timing of jaundice in relation to HE, other symptoms of CLD, and a drug and travel history to establish a causative agent. HE is graded and should be clearly documented for all patients:

• •Grade I: mild confusion, decreased attention, irritability
• •Grade II: disorientation, drowsiness, inappropriate behaviour
• •Grade III: somnolent but rousable, incoherent
• •Grade IV: coma

The laboratory tests that should be performed in all patients when a diagnosis of ALF is considered are detailed in Table 1. All women of childbearing age should have a pregnancy test. Imaging will often include ultrasound and triple phase CT of the liver. These can show changes in liver echogenicity, splenomegaly, ascites, liver surface nodularity, collateral vessel formation, hepatomegaly or liver atrophy, reversed portal blood flow, and vascular patency. It is important to note that initial studies can be normal and therefore serial images should be considered.^9,10

Table 1.

Laboratory tests for patients presenting with ALF; the aim is to identify the hepatic and extrahepatic impact of ALF and the underlying aetiology. ALF, acute liver failure; AKI, acute kidney injury; INR, international normalised ratio; HE, hepatic encephalopathy.

		Reasoning for test
Intrahepatic
Liver function test	Aspartate aminotransferase	Severity and presence of hepatocellular and cholestatic injury
	Alanine transaminase
	Alkaline phosphatase
	Gamma glutamyl transferase
	Bilirubin
	Albumin
Coagulation	INR/prothrombin time	Synthetic marker of liver function
Arterial blood gas	Lactate	Lactate chiefly metabolised by liver and concentrations are increased in liver damage
	Ammonia	Ammonia is the most important neurotoxin responsible for HE. It is metabolised to urea by the liver and excreted in the urine. Serum concentrations are increased in liver damage
Extrahepatic
Biochemistry	Electrolytes; sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate	Assessment of AKI and another organ dysfunction. General metabolic derangements common in ALF
	Glucose
	Urea/creatinine
	Lactate dehydrogenase
Haematology	Full blood count	Anaemia, thrombocytopenia, bleeding, concurrent infection
	Blood group
Others	Lipase	Assessing for complications of ALF; 1 in 20 patients develop pancreatitis (particularly in paracetamol overdose)
	Amylase
	Creatine kinase
Identification of aetiology
Serological	Hepatitis A, B, C, and E, Epstein–Barr virus, herpes simplex virus, varicella zoster virus and HIV 1 and 2	Viral causes
Autoimmune	Antinuclear antibodies	Autoimmune hepatitis
	Anti-smooth muscle antibodies	Autoimmune hepatitis
	Anti-mitochondrial antibodies	Primary sclerosing cholangitis/autoimmune hepatitis
	Copper studies/caeruloplasmin	Wilson's disease
	Immunoglobulins
Drugs/toxins	Paracetamol	Identification of toxin-related aetiology
	Urine analysis

Referral to a specialist centre

Acute liver failure is a rapidly progressive condition, and early escalation to critical care is essential. The care of these patients should be discussed within a multidisciplinary team involving hepatology, critical care, and the transplant team. This can offer insight into the trajectory of the condition and inform the timing of transfer to a specialist centre. Thresholds for referral vary but generally include an INR >3.0, or prothrombin time (PT) >50 s or increasing; HE; hyperlactataemia or hypotension despite resuscitation; pH <7.35; acute kidney injury (AKI); bilirubin >300 μmol L⁻¹; and shrinking liver volume on imaging.¹¹

Treatment

Airway and breathing

Early elective tracheal intubation of patients with higher grades of HE (III/IV) is recommended for airway protection especially if being transferred. This allows protection from aspiration, control of agitation, and optimal management of ICP. Standard airway strategies to minimise increases in ICP should be used during the intubation process. Further unwarranted surges in ICP can be avoided by using lung protection ventilation, with tidal volumes of 6 ml kg⁻¹ with a maximum of 8 ml kg⁻¹ to maintain Pco₂ between 4.5 and 5.5 kPa, and appropriate concentrations of PEEP.¹ A balanced approach must be taken with optimisation of ventilation versus optimal cerebral perfusion and avoiding increases in ICP.^1,9,12 Standard bundles to avoid ventilator associated pneumonia should be strictly adhered to as these patients are at a greater risk of developing infections.^1,9 The incidence of acute respiratory distress syndrome (ARDS) is low in this specific patient population, and veno-venous extra corporal membrane oxygenation (ECMO) is an option in selected patients in centres with expertise in both ECMO and ALF.^1,13 However, the use of ECMO is very rare, and the subgroup of patients for which it may be useful has not been defined and requires further studies.

Circulation

Most patients with ALF have profoundly reduced systemic vascular resistance presenting with vasodilatory shock, high cardiac output state, and a clinical picture similar to that seen in SIRS or sepsis.⁹ Therefore, the aim of cardiovascular support is to restore circulating volume and enhance oxygen delivery to tissue by targeting a MAP >65 mmHg.¹ A higher MAP of 80 mmHg should be targeted if there are signs of raised ICP and for patients with uncontrolled chronic hypertension. A balanced crystalloid solution is recommended for volume restoration, with regular monitoring of acid–base status and plasma electrolytes. Although albumin administration does not have an impact on mortality, it does improve haemodynamic status and can also be used as a colloid volume expander.¹ Starch substances should be avoided because of the increased risk of needing renal impairment.¹ Fluid management should be directed by cardiac output monitoring, the choice of device determined by the individual unit preference.⁹ Noradrenaline (norepinephrine) is recommended as first-line agent for vasopressor support.¹ Terlipressin, a commonly used splanchnic vasoconstrictor in patients with cirrhosis, has been implicated in potentially worsening ICP and is not widely used in ALF.¹⁴ Adrenaline (epinephrine) may be added as an inotrope where there is evidence of a cardiac dysfunction/failure. Cortisol deficiency is common in ALF and the degree of deficiency correlates with disease severity.¹⁵ Supraphysiological doses of cortisol have been shown to reduce vasopressor requirements s but they do not improve survival and increase the risk of infection.¹⁶

Renal

Acute kidney injury occurs in 40–85% of patients with ALF. The incidence is higher in ALF secondary to paracetamol poisoning because of direct paracetamol-mediated tubular toxicity. ALF associated with AKI is associated with worsening of HE and poorer outcomes.¹⁷ Risk factors for developing AKI include older age, paracetamol-induced ALF, hypotension, SIRS, and infections.¹ Early initiation of renal replacement therapy (RRT) is advised for renal support but also for non-renal indications including hyperammonaemia (ammonia concentrations >150 μmol L⁻¹), sodium imbalances, temperature, and metabolic control.¹ Continuous RRT is preferred to prevent cerebral complications related to fluid shifts. Refractory hyperammonaemia has been shown to respond to higher intensity ultrafiltration with rates of up to 60–90 ml kg⁻¹ h⁻¹ with the additional benefit of a reduction in vasopressor requirements.¹⁸ This is in contrast to septic shock where higher intensity ultrafiltration has not been shown to be effective. The need for and choice of anticoagulation of the circuit remains controversial. Evidence suggests frequent clotting of circuits, and therefore despite coagulopathy most patients will require anticoagulation. Unfractionated heparin, prostacyclin, or both are the most common options.¹⁹ Regional citrate anticoagulation is generally avoided because of the diminished ability of the liver to metabolise the citrate load. It is used in patients with liver failure in some centres, but careful monitoring is required.^1,20

Central nervous system

Intracranial hypertension as a result of cerebral oedema is a major concern in patients with ALF, with a mortality of 55%. However, the incidence of ICH in the UK has decreased from 76% in the 1980s to 19.8% between 2004–8 because of improved understanding of the pathophysiology, pre-emptive institution of targeted cerebral care, and improved organ support.⁷ Risk factors for ICH include hyperacute or acute presentation, younger ages, renal and cardiac dysfunction, systemic inflammatory response, and persistent ammonia concentrations > 200 μmol L⁻¹.^1,12 Increased ammonia concentrations lead to astrocyte swelling, mitochondrial dysfunction, and cerebral oedema, and correlate with the development of raised ICP and HE.¹² Therefore, patients should have regular monitoring of arterial ammonia, as concentrations >124 μmol L⁻¹ predict mortality with an accuracy of 77.5%.¹² Clinical signs have low sensitivity and specificity for detecting increases in ICP, and in ICU are masked by medication and organ support. Abnormal pupillary responses, spasticity, extensor posturing, and Cushing's reflex are all late signs of raised ICP. Overall, 25% of patients with ALF have clinical signs of seizure activity with the incidence of subclinical activity higher, but there is no evidence to support using prophylactic anticonvulsant therapy.¹² Invasive ICP monitoring is associated with a 1–4% risk of non-fatal and a 1% risk of fatal haemorrhage. The incidence varies on operator and centre expertise and placement location, and there is little evidence of its impact on long-term survival.¹² The use of invasive ICP monitoring is therefore only recommended for patients at a very high risk of developing ICH.^1,2 Other means of monitoring ICP include jugular venous oxygen saturations, transcranial Doppler, optic nerve sheath diameter, and near-infrared spectrophotometry (NIS); however, the accuracy of these is not fully established.¹² CT is useful to exclude other aetiologies but is insensitive to detecting increased ICP. MRI is more sensitive but is often not logistically possible. The management and prevention of raised ICP includes reducing cerebral oxygen consumption through adequate sedation, maintaining normocapnia and normoglycaemia, minimising venous congestion through 30° head elevation and loosening endotracheal ties, and avoiding hyperthermia. Serum sodium should be maintained between 145 and 150 mmol L⁻¹ using boluses or a continuous infusion of sodium chloride 30% if needed.^1,9 RRT should be initiated early with the aim of keeping the serum ammonia <100 μmol L⁻¹.⁹ Acute surges of ICP can be managed with a bolus of hypertonic saline (200 ml 3% or 20 ml of 30%) or rarely mannitol (150 ml, 20%) given over 20 min with the aim of keeping sodium ≥150 mmol L⁻¹ and osmolality <320 mOsm L⁻¹.^1,2 In resistant cases, a short period of hyperventilation can be used to reduce Paco₂ to ≤4 kPa. There is little evidence for therapeutic cooling in the context of ALF and raised ICP. The goal is to avoid fever and maintain a core temperature of 35–36°C. Profound hypothermia (≤33° C) has been shown to reduce severe refractory ICH and should be reserved as a rescue intervention in selected patients.^1,2

Coagulation

Acute liver failure often presents with deranged INR/PT, thrombocytopenia, and reduced circulating pro- and anticoagulant proteins and fibrinogen concentrations. These patients are therefore often assumed to have a higher incidence of spontaneous and procedure-related bleeding, but this is often not the case.² Reduced synthesis of procoagulant clotting factors by the diseased liver is compensated by a simultaneous reduction of natural anticoagulants (proteins C and S and antithrombin) and an increased expression of endothelium derived factor VIII, Von Willebrand factor and circulating procoagulant microparticles. This collectively leads to a state of rebalanced haemostasis.²¹ Point-of-care (POC) tests of coagulation such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM) have demonstrated complex coagulation profiles in ALF that do not correlate with PT derangement: a hypocoagulable state in 20%, normal in 45%, and a hypercoagulable in 35%.²¹ POC testing is therefore recommended, as standard laboratory measurements of coagulation such as INR measurements may fail to reveal the true haemostatic state. Routine correction of INR/PT should be avoided as these are important markers of synthetic liver function. Platelets and fibrinogen are more sensitive indicators of bleeding risk and should be corrected as required. For insertion of intravascular catheters, a platelet count of >30×10⁹ L⁻¹ and a fibrinogen concentration of >1–1.5 g L⁻¹ are generally adequate, but for invasive ICP monitoring or if there is active haemorrhage it is reasonable to correct all clotting including INR, platelets and fibrinogen.

Sepsis

Acute liver failure is associated with an immune dysfunction leading to altered macrophage and neutrophil function, reduction in complement and impaired phagocytosis, and opsonisation.^1,9 Systemic inflammatory response syndrome without infection itself worsens HE and leads to generally poorer outcomes.²² Sepsis is now considered the leading cause of death in ALF, but may also prevent patients from receiving a transplant or complicate the postoperative recovery period. Bacteraemia is reported in 80% of cases with pneumonia being the most common site (50%) followed by urinary tract infection (22%) and catheter-induced bacteraemia (12%). Gram-negative enteric bacilli and gram-positive cocci are the most frequently isolated. Fungaemia is seen in 32% of cases of ALF with Candida species being the main culprit.²² These patients will also frequently have bacterial co-infections. Reactivation of viral infections is also seen, particularly cytomegalovirus (CMV).¹ Diagnosis can be challenging as clinical features such as increased temperature and increased inflammatory biomarkers can be absent; therefore, a high level of suspicion and regular microbiological surveillance are recommended. Prophylactic use of antibiotics and antifungals does not have an impact on survival outcome but does reduce the incidence of sepsis and HE, and is therefore recommended.^1,9 This is particularly important for those listed for super urgent liver transplants as development of infections may lead to delisting.¹

Metabolic and nutrition

Hypoglycaemia is frequently present in patients with ALF and is associated with increased mortality. The clinical presentation is often similar to that of HE, and therefore blood glucose should be monitored regularly. Prompt treatment should be provided in the form of i.v. low volume, high concentration glucose solutions, avoiding infusion of large volume of hypotonic solutions, which could worsen cerebral oedema and hyponatraemia.^2,9 Derangements of magnesium, calcium, potassium, and phosphate are also frequently observed and should be corrected appropriately.¹

Acute liver failure leads to increased energy expenditure and protein catabolism; early initiation of nutritional support is necessary. Enteral feeding is often the preferred route with a daily calorie target of 25–30 kcal kg⁻¹ day ⁻¹.⁹ Prokinetics are frequently required to aid absorption, which is often impaired because of a variety of ICU-related factors. Postpyloric feeding can be considered if absorption remains suboptimal and is preferred to parental feeding, which is associated with higher rates of infections. Some liver units will continue to give 1.0–1.5 g kg⁻¹ day⁻¹ of enteral protein with regular monitoring of ammonia, adjusting intake as appropriate.² Stress ulcer prophylaxis in the form of a proton pump inhibitor (PPI) is frequently given to patients, and consideration should be given to stopping this once enteral feeding has been established.¹

Specific therapies

N-acetyl cysteine

There is strong evidence for the early use of N-acetyl cysteine (NAC) in patients with established paracetamol overdose.¹ It provides cysteine, which is a glutathione precursor. This neutralises N-acetyl-p-benzoquinone imine (NAPQI), which is responsible for hepatocyte toxicity. In 2012 the UK's Commission on Human Medicine (CHM) offered simpler guidelines with a single nomogram treatment line (patient risk stratification no longer required) resulting in greater treatment consistency among different centres. There is also evidence of improved transplant-free survival in non-paracetamol-related ALF when using NAC, specifically in those in the early stages of the disease with lower grades of HE.²³

AIH and steroids

Autoimmune hepatitis is a hepatic necrotic-inflammatory condition that often presents chronically, but approximately 20% of cases present as ALF with extensive necrosis.²⁴ The diagnosis is often challenging, and a significant proportion of patients will require a LT. If diagnosis is suspected, early referral to a specialist centre is crucial for a diagnostic biopsy and potential steroid therapy.

Antivirals and hepatitides

There is some evidence for the use of antiviral drug lamivudine in ALF secondary to hepatitis B infection. This has improved survival outcomes, but it is important that the therapy is initiated early before advanced stages of ALF develop. There are less robust data on the use of other antivirals such as entecavir and tenofovir. There is currently no evidence for using interferon in these specific patients.²⁵ There is currently no evidence to support the use of antivirals in ALF secondary to hepatitis E.

Wilson's disease and chelating agents

d-Penicillamine is a chelating agent that promotes the urinary excretion of copper. Its early use has been shown to be effective in restoring liver function and preventing disease progression in the context of ALF, potentially avoiding the need for LT.²⁶

Other therapeutic options

Plasma exchange

Plasma exchange is often used for a range of other immunologically mediated conditions and replaces the patient's plasma with donor fresh frozen plasma. Multiorgan failure associated with ALF results in a range of circulating proinflammatory cytokines because of SIRS, and the accumulation of metabolites and toxins exacerbated by hepatocyte death. High volume plasma exchange (HVP) is defined as exchange of 15% of ideal body weight. In fact, HVP has been shown to increase overall survival in ALF, but specifically in patients who do not undergo emergency transplantation because of contraindications, and those patients who have deteriorated while waiting for a graft.²⁷

Mechanical assist devices

These devices are broadly divided into biological and non-biological and are not used in routine clinical settings.²⁸ The non-biological devices work on the principle of haemodialysis using an artificial membrane to detoxify the blood. Molecular adsorbent recirculating system (MARS) and single pass albumin dialysis (SPAD) use albumin-based dialysate across a highly selective membrane (<50 kDa). These devices result in improved haemodynamic function and HE but have failed to show any survival benefit in ALF.¹ The biological devices are much more complex and consist of porcine or human hepatic cells. These devices aim to enable not only clearance of toxins but also to support hepatocyte function. Two devices, HepatAssist and extracorporeal liver assist device (ELAD), are currently only used in clinical trial settings.

Liver transplantation

Liver transplantation has been a significant leap in the management of ALF with dramatic effects on survival outcomes. Ten percent of all liver transplants are performed for ALF, and the 5 yr survival of these patients in the UK is 82% (83% for elective liver transplant).²⁹ Risk factors for poorer outcomes after transplantation include age > 60 yrs, cardiac dysfunction, high vasopressor requirements, and Fio₂ >0.8 preoperatively.⁹ Patients with ALF meeting the criteria are listed for superurgent transplantation, and the most frequently used King's College criteria for patient selection are shown in Table 2. It is important that prognostication is performed early and discussed with a specialist centre. Auxiliary LT is also an option in selected patients and offers the benefit of the patient not having to take lifelong immunosuppressants.³⁰

Table 2.

King's College Hospital, London criteria for liver transplantation in ALF (based on the current UK Criteria).⁹ ALF, acute liver failure; INR, international normalised ratio; HE, hepatic encephalopathy.

ALF caused by paracetamol toxicity	ALF not caused by paracetamol toxicity
pH <7.25 (after 24 h of fluid resuscitation)Lactate >3.0 mmol L−1 (after 24 h of fluid resuscitation)	Prothrombin time >100 s (INR > 6.5)
Or	Or
All of the following: •Prothrombin time >100 s (INR >6.5) •Creatinine >300 μmol L−1 •Grade III or IV HE	Any three of the following: •Age <10 or >40 yr •Seronegative or drug-induced ALF •Jaundice to encephalopathy >7 days •Prothrombin time >50 s (INR >3.5) •Bilirubin >300 μmol L−1

Liver transplantation is contraindicated for patients with irreversible brain damage, malignancy, or uncontrolled sepsis. It also commits the recipient to a lifetime of immunosuppression and therefore even when listed, continuous assessment of suitability should be made within a multidisciplinary setting. Patients who recover spontaneously have better outcomes compared with those who have a transplant. If there are signs of clinical improvement or progressive irretrievable deterioration (irreversible brain damage, severe infections, and worsening haemodynamic parameters), it is acceptable to postpone the transplant.

Conclusions

Acute liver failure is an acute severe life-threatening condition that carries a high mortality but is potentially reversible. The outcomes have improved significantly over the last few decades with a better understanding, improvements in intensive care and increased availability of transplants.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Declaration of interests

The authors declare that they have no conflicts of interest.

Biographies

Riaz Aziz FRCA MRCP DTM&H is a National Institute for Health Research (NIHR) academic clinical fellow in intensive care medicine and anaesthesia.

Jennifer Price BSc FRCA EDIC FFICM is a consultant in anaesthesia and intensive care at the Royal Free Hospital. She has an interest in acute liver failure and is a Faculty tutor for FFICM.

Banwari Agarwal MD FRCA FRCP EDIC FFICM, is a consultant in intensive care at the Royal Free Hospital and an honorary associate professor at the Institute of Liver & Digestive Health, University College London. He has a special interest in critical care management of patients with liver failure including liver transplantation and extracorporeal liver support systems and has more than 50 publications in this area.

Matrix codes: 1A01, 2C07, 3C00