Acute liver failure

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Chapter 47 ACUTE LIVER FAILURE

• Acute liver failure (ALF) is defined as the rapid development of coagulopathy and mental status changes in a patient with deteriorating liver function tests with no known preexisting liver disease.

• The most common causes of ALF in the Western world include paracetamol hepatotoxicity, idiosyncratic drug toxicity and viral hepatitis.

• The clinical features of ALF result from reduced hepatocellular function and complications involving other organs, including hepatic encephalopathy, cerebral oedema and intracranial hypertension, coagulopathy and bleeding, sepsis, multiorgan failure syndrome and metabolic derangements.

• Initial evaluation is aimed at determining the underlying aetiology, assessing the severity of the illness and prognosis and identifying complications.

• Principles of management include intensive medical management with general supportive measures, aetiology-specific management when appropriate and consideration of early referral and transfer to a specialist transplant unit.

• Liver transplantation has dramatically improved outcomes for patients with ALF, with overall survival rates now greater than 60%.

DEFINITION

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.

CAUSES OF ACUTE LIVER FAILURE

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 (acetaminophen) hepatotoxicity

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.

Idiosyncratic drug toxicity

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.

TABLE 47.1 Aetiologies of acute liver failure

Drug toxicity

• Paracaetamol (acetaminophen)

• Idiosyncratic drug reactions

– Ampicillin-clavulanate

– Doxycycline

– Salicylates

– Non-steroidal antiinflammatory drugs

Other causes

• Autoimmune hepatitis

• Viral hepatitis

– Hepatitis D virus

– Hepatitis B virus

– Hepatitis E virus

– Hepatitis A virus

• Wilson’s disease

• HELLP syndrome

• Acute fatty liver of pregnancy

• Ischaemic hepatitis

• Heat stroke

• Budd-Chiari syndrome

• Amanita phalloides mushroom toxin

Herbal agents

HELLP syndrome = haemolysis elevated liver enzymes low platelet syndrome.

Viral hepatitis

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.

Miscellaneous

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.

CLINICAL FEATURES AND MAJOR COMPLICATIONS

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