Chapter 47 ACUTE LIVER FAILURE
Acute liver failure (ALF), or fulminant hepatic failure, is defined as the rapid development of coagulopathy (INR ≥1.5) and mental status changes (encephalopathy) in a patient with rapidly deteriorating liver function tests without known preexisting liver disease. The presence of encephalopathy distinguishes ALF from severe acute hepatitis.
ALF is a broad term encompassing both fulminant hepatic failure (FHF) and subfulminant hepatic failure (or late-onset hepatic failure). FHF is generally used to describe the development of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver. Subfulminant hepatic failure refers to patients with liver disease for up to 26 weeks prior to the development of hepatic encephalopathy. Some patients with previously unrecognised chronic liver disease decompensate and present with liver failure; although this is not technically FHF, discriminating this at the time of presentation may not be possible.
Acute liver failure represents a syndrome that is the final common pathway for a variety of liver insults. A cause for ALF can be established in approximately 60%–80% of cases. There is a marked worldwide variation in the relative incidence of the various underlying causes. For example, in Australia, the UK and the USA, medications (e.g. paracetamol) and idiosyncratic drug reactions are the most commonly identified aetiologies. In other parts of the world, including Asia, acute viral hepatitis is a leading cause of ALF.
Paracetamol toxicity accounts for approximately 40% of cases of ALF in the UK and the US. Hepatotoxicity is dose-related; most ingestions leading to ALF exceed 10 g/day and mortality is higher with doses over 48 g. While most episodes result from deliberate acts of self-harm, a significant proportion of cases result from therapeutic use. Factors increasing susceptibility to hepatotoxicity include regular alcohol consumption, antiepileptic therapy, preexisting hepatic dysfunction and malnutrition.
A variety of prescription drugs, including various antiepileptics (e.g. phenytoin, sodium valproate), non-steroidal antiinflammatory drugs (e.g. diclofenac) and antibiotics (e.g. isoniazid) have been implicated in acute liver failure (Table 47.1). Most cases occur within the first 4–6 weeks of initiating treatment, but can occur years after the drug is commenced. Certain herbal preparations and other nutritional supplements have been found to cause liver injury. In addition, a variety of illicit substances, including synthetic amphetamines, have been linked to ALF.
|Drug toxicity||Other causes|
HELLP syndrome = haemolysis elevated liver enzymes low platelet syndrome.
Hepatitis A virus and hepatitis B virus are the chief causes of ALF in India and other parts of the developing world. However, ALF is an uncommon complication of viral hepatitis, occurring in 0.2%–4% of cases depending on the underlying aetiology. The risk of developing ALF from hepatitis E approaches 20% in pregnant women. Other viral aetiologies of ALF include hepatitis D virus coinfection or superinfection (Table 47.1), Epstein-Barr virus, cytomegalovirus, herpes simplex virus and varicella zoster.
There are a number of other less common causes of ALF. Pregnancy-related liver disease may result in ALF, usually in the third trimester. A variety of presentations may be seen with thrombocytopenia and features of pre-eclampsia often present. Wilson’s disease may present as ALF, typically in young patients accompanied by the abrupt onset of haemolytic anaemia. The fulminant presentation carries a poor prognosis without transplantation. Autoimmune hepatitis, Budd-Chiari syndrome, toxins (mushroom poisoning, aflatoxins), ischaemic hepatitis and malignant infiltration of the liver are other infrequent causes of ALF (Table 47.1). A definite cause is unable to be identified in approximately 15%–40% of cases of ALF worldwide.
The clinical features of ALF result from reduced hepatocellular function and from complications involving other organs. Non-specific symptoms such as nausea, vomiting and malaise are common initially, closely followed by the onset of jaundice.
Hepatic encephalopathy is a defining characteristic of ALF. Severity is graded on a scale of 1 to 4. In stage 1, patients have subtle impairments in concentration and altered sleep patterns. Stage 2 is marked by drowsiness and confusion often accompanied by asterixis or tremor. Stage 3 is marked by increasing somnolence and incoherence, which progresses to frank coma in stage 4. Hyperreflexia, clonus and muscular rigidity may be present in the latter stages.
Progressive cerebral oedema with the development of elevated intracranial pressure (ICP) plays a major role in the pathogenesis of this condition and has long been recognised as the most serious complication of ALF. The classic signs of raised ICP include systemic hypertension, bradycardia and irregular respirations (Cushing’s triad). Intracranial hypertension can result in cerebral hypoperfusion and hypoxia leading to irreversible neurologic damage, uncal herniation and brain death. Direct intracranial pressure monitoring is commonly used in patients with ALF and severe encephalopathy.