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Acute Liver Failure J G O’Grady 148 Postgrad Med J: first published as 10.1136/pgmj.2004.026005 on 4 March 2005. Downloaded from REVIEW Acute liver failure J G O’Grady ............................................................................................................................... Postgrad Med J 2005;81:148–154. doi: 10.1136/pgmj.2004.026005 Acute liver failure is a complex multisystemic illness that account for most cases, but a significant number of patients have no definable cause and are evolves quickly after a catastrophic insult to the liver classified as seronegative or of being of indeter- leading to the development of encephalopathy. The minate aetiology. Paracetamol is the commonest underlying aetiology and the pace of progression strongly cause in the UK and USA.2 Idiosyncratic reac- tions comprise another important group. influence the clinical course. The commonest causes are paracetamol, idiosyncratic drug reactions, hepatitis B, and Viral seronegative hepatitis. The optimal care is multidisciplinary ALF is an uncommon complication of viral and up to half of the cases receive liver transplants, with hepatitis, occurring in 0.2%–4% of cases depend- ing on the underlying aetiology.3 The risk is survival rates around 75%–90%. Artificial liver support lowest with hepatitis A, but it increases with the devices remain unproven in efficacy in acute liver failure. age at time of exposure. Hepatitis B can be associated with ALF through a number of ........................................................................... scenarios (table 2). The commonest are de novo infection and spontaneous surges in viral repli- cation, while the incidence of the delta virus cute liver failure (ALF) is a complex infection seems to be decreasing rapidly. multisystemic illness that evolves after a Vaccination should reduce the incidence of Acatastrophic insult to the liver manifesting hepatitis A and B, while antiviral drugs should in the development of a coagulopathy and ameliorate replication of hepatitis B. Hepatitis C encephalopathy within a short period of time. is rarely recognised as the sole cause of ALF. ALF is a heterogenous condition incorporating a Hepatitis E is common in parts of Asia and Africa range of clinical syndromes, principally deter- and the risk of developing ALF increases to over mined by the underlying aetiology, the age of the 20% in pregnant women, being particularly high patient, and the duration of time over which the during the third trimester. Unusual causes of disease evolves. There are a number of classifica- viral ALF include herpes simplex 1 and 2, tions of ALF in use but in the UK the terms herpesvirus-6, varicella zoster, Epstein-Barr hyperacute, acute, and subacute are used to virus, and cytomegalovirus. define the onset of encephalopathy within Seronegative hepatitis is the commonest pre- http://pmj.bmj.com/ 7 days, 8–28 days, and more than 28 days, sumed viral cause in some parts of the western respectively.1 The natural history of the condition world, although there is little evidence to is very variable within this range and survival implicate a viral infection. Middle aged women rates without transplantation range from 10% to are most commonly affected and it occurs 90% for different cohorts. Integrated multidisci- sporadically. The diagnosis is one of exclusion. plinary protocols that use liver transplantation are now achieving considerably improved survi- Drugs on September 26, 2021 by guest. Protected copyright. val rates in the range from 40% to 90% Paracetamol overdose accounts for about 40% of depending on the underlying aetiology. cases of ALF in the UK but is falling since legislation limited the amounts that can be purchased over the counter.2 It is usually taken with suicidal or parasuicidal intent, but up to The components of the management strategy 8%–30% cases are consequent upon therapeutic are: use. Factors increasing susceptibility to para- cetamol toxicity include regular alcohol con- N determination of aetiology sumption, antiepileptic therapy (via enzyme N assessment of the severity of the disease induction), and malnutrition. ALF develops in and the associated prognosis, only 2%–5% of those taking overdoses,. There is N prevention or treatment of complications some dose dependent relation with mortality, which is highest at doses over 48 grams. ....................... N liver transplantation when spontaneous Idiosyncratic drug reactions usually develop Correspondence to: survival is considered unlikely during the first exposure to the drug and the Dr J G O’Grady, Institute N possible use of liver support devices. of Liver Studies, King’s leading candidates are listed in box 1. The College Hospital, Denmark diagnosis is usually made on the basis of a Hill, London SE5 9PJ, UK; temporal relation between exposure to the john.o’[email protected] drug and the liver injury. Estimates of the Submitted 24 June 2004 CAUSES AND EPIDEMIOLOGY risk of developing ALF as a result of an Accepted 11 August 2004 There is considerable geographical variation in idiosyncratic reaction range from 0.001% for ....................... the causation of ALF (table 1). Viruses and drugs non-steroidal anti-inflammatory drugs to 1% www.postgradmedj.com Acute liver failure 149 Postgrad Med J: first published as 10.1136/pgmj.2004.026005 on 4 March 2005. Downloaded from Table 1 Geographical variation in the aetiology of ALF UK US France India Japan Paracetamol 54 40 2 – – Drug reactions 7 12 15 5 – Seronegative 17 17 18 24 45 Hepatitis A or B 14 12 49 33 55 Hepatitis E – – – 38 – Other causes 8 19 16 – – Data shown as percentages. Table 2 ALF associated with hepatitis B HbsAg IgM anti-core HbeAg HbeAb HBV DNA Comment Acute infection Variable Positive Variable Variable Usually negative Hyperactive response, immune mediated Seroconversion Positive Negative Negative Positive Negative Immune Replication surge Positive Negative Variable Variable High Spontaneous or after immunsuppression Delta super-infection Positive Negative Variable Variable Low New positive serology for delta virus for the isoniazid/rifampicin combination. Ecstasy (3, 4 methyl- The Budd-Chiari syndrome may present with ALF and the enedioxymetamphetamine—a synthetic amphetamine) has diagnosis is suggested by hepatomegaly and confirmed by the been associated with a number of clinical syndromes demonstration of hepatic vein thrombosis. Malignancy ranging from rapidly progressive ALF associated with infiltration, especially with lymphoma, is also typically malignant hyperpyrexia to subacute liver failure. associated with hepatomegaly. Ischaemic hepatitis is being increasingly recognised as a cause of ALF, especially in older patients. Box 1 Drugs causing ALF Category 1—commoner causes N Paracetamol, halothane, isoniazid/rifampicin, non- N Paracetamol remains the commonest aetiology but the steroidal anti-inflammatory drugs (NSAIDs), sulphon- incidence is falling in the UK amides, flutamide, sodium valproate, carbamazepine, N Seronegative hepatitis is the next biggest group Ecstasy N Hepatitis A and B should decrease with vaccination Category 2—rarer causes programmes http://pmj.bmj.com/ N Benoxyprofen, phenytoin, isoflurane , enflurane, tetra- N Idiosyncratic drug reactions comprise the other main cycline, allopurinol, ketoconazole, monoamine oxi- aetiological group dase inhibitors (MAOIs), disulphiram, methyldopa, amiodarone, tricyclic antidepressants, propylthiouracil, gold, 2,3,-dideoxyinosine (ddI) DIAGNOSIS AND PROGNOSIS The aetiology of ALF must be accurately identified and the appropriate investigations are outlined in table 3. A liver on September 26, 2021 by guest. Protected copyright. Other aetiologies biopsy is not usually necessary other than to identify the There are three recognised syndromes of liver injury that occasional case of malignant disease. The underlying usually occur during the third trimester, although a aetiology is a powerful determinant of prognosis with a considerable degree of overlap exists. Acute fatty liver of spontaneous survival rate ranging from 10% to 90%. The pregnancy preferentially affects primagravids carrying a male grade of encephalopathy also correlates strongly with out- fetus. The HELLP syndrome is defined by the co-existenxce of come (both the grade at presentation and the maximum haemolysis, elevated liver enzymes, low platelets. ALF grade attained). The prognosis deteriorates further when complicating pre-eclampsia or eclampsia is characterised by grade 4 encephalopathy is complicated by cerebral oedema, high transaminase activities. and even further when the latter coexists with renal failure.4 Wilson’s disease may present as ALF, usually during the Reliance on the development of these clinical complica- second decade of life and is characterised clinically by a tions to determine prognosis is not helpful when defining the Coomb’s negative haemolytic anaemia and demonstrable scope and application of liver transplantation and early Kayser-Fleischer rings in most cases. Poisoning with Amanita indicators of prognosis are required. Furthermore, patients phalloides (mushrooms) is most commonly seen in central with subacute liver failure have very poor prognoses despite Europe, South Africa, and the west coast of the United States. not developing cerebral oedema or renal failure. Deter- Severe diarrhoea, often with vomiting, starts five or more mination of prognosis drives two fundamental management hours after ingestion of the mushrooms and liver failure issues—that is, the need for referral to specialist centres
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