Acute liver failure is due to necrosis of the liver leading to loss of liver function. The definition includes coagulopathy and encephalopathy. Other organs are often affected and there is a high mortality rate despite intensive care support. The initial clinical features are subtle with poor feeding, difficulty waking and poor temperature control, which can be difficult to detect in young infants. Initial investigations will show prolonged prothrombin time, hypoglycaemia, increased transaminases and bilirubin. A neonate with acute liver failure or liver dysfunction should be referred immediately to a tertiary paediatric liver centre for further advice, investigations and management. Many will require timely transfer for specialised care and consideration for transplantation. The most common causes are infection and metabolic disease (Tables 2.1 and 2.2) whilst liver vascular disease e.g. haemangioendotheliomas also present as an acutely ill baby with hepatomegaly, preserved liver biochemistry, heart failure and consumptive coagulopathy.