Liver failure describes severe loss of hepatic function such that the liver can no longer adequately perform essential metabolic, synthetic, detoxification and regulatory tasks. It is a functional state rather than a single disease and can arise from many underlying disorders. Liver failure may be acute, developing over a short period in a previously functioning liver, or chronic, developing after longstanding liver disease such as cirrhosis.
The liver normally synthesises albumin and many coagulation proteins, processes bilirubin, metabolises medicines and hormones, regulates nutrients and participates in immune and detoxification processes. Failure of these functions can produce jaundice, coagulopathy, fluid accumulation, altered consciousness, metabolic abnormalities and multiorgan dysfunction. Severe liver failure is a medical emergency requiring specialist assessment.
Acute liver failure is characterised by rapid deterioration of hepatic function, typically accompanied by impaired coagulation and altered mental status in a person without established cirrhosis. Causes include drug-induced liver injury, particularly severe poisoning with paracetamol, acute viral hepatitis, autoimmune hepatitis, vascular disorders and other toxic or metabolic causes. Because acute liver failure develops rapidly, complications can progress over hours or days, including cerebral oedema, hypoglycaemia, kidney injury, infection, abnormal bleeding and circulatory instability. The distinction from acute worsening of chronic liver disease is clinically important because the underlying anatomy, prognosis and treatment pathways differ. Acute liver failure may occasionally be reversible if the cause is rapidly identified and treated, but some patients require urgent liver transplantation.
Chronic liver failure generally develops after prolonged liver injury and is often associated with cirrhosis. Progressive loss of functioning hepatocytes combines with architectural distortion and portal hypertension to produce a broad range of systemic consequences. Patients may develop jaundice, ascites, oedema, variceal bleeding, hepatic encephalopathy, muscle wasting and increased susceptibility to infection. The term end-stage liver disease is often used for advanced chronic hepatic dysfunction in which normal liver function can no longer be adequately maintained. Chronic liver failure can worsen suddenly through an acute precipitating event such as infection, gastrointestinal bleeding, alcohol-related injury, medication toxicity or another systemic insult. Such acute-on-chronic deterioration can be life-threatening and may require intensive specialist management.
Symptoms and signs reflect the particular functions that have become impaired. Jaundice occurs when bilirubin accumulates, while ascites and peripheral oedema are influenced by portal hypertension, sodium and water retention and reduced albumin. Easy bruising and abnormal bleeding can result from impaired synthesis of coagulation proteins, although haemostasis in advanced liver disease is complex. Hepatic encephalopathy can cause confusion, sleep disturbance, impaired concentration, altered behaviour, drowsiness and coma. Nausea, poor appetite, fatigue and weight loss may occur. In advanced disease, infection, kidney dysfunction, low blood pressure and electrolyte abnormalities can compound hepatic impairment. Vomiting blood or passing black stools may indicate gastrointestinal variceal bleeding and requires emergency care, as does sudden confusion in a person with established cirrhosis.
Diagnosis involves assessing liver injury, liver function, the underlying cause and complications. Blood tests commonly include bilirubin, aminotransferases, alkaline phosphatase, albumin, clotting measures and full blood count, while renal function and electrolytes are important because kidney injury commonly accompanies severe hepatic dysfunction. Imaging can assess liver structure, blood flow and complications such as ascites or portal hypertension. Additional investigations depend on the suspected cause and may include viral testing, autoimmune markers, metabolic investigations and toxicology. In acute liver failure, the international normalised ratio and neurological state are especially important indicators of severity. Clinicians must also determine whether the patient has previously unrecognised chronic liver disease because this changes interpretation and management.
Treatment depends fundamentally on whether the failure is acute or chronic and what caused it. Acute paracetamol toxicity can be treated with N-acetylcysteine, while selected viral, autoimmune, vascular or metabolic causes have their own targeted treatments. Supportive critical care may be needed to maintain glucose, circulation, electrolyte balance and cerebral protection while the liver recovers or transplantation is arranged. Chronic liver failure requires treatment of the underlying disease and careful management of portal hypertension, ascites, encephalopathy, infection, nutrition and other complications. Once irreversible end-stage liver failure develops, liver transplantation can replace the failing organ and may be life-saving in appropriately selected patients.
Liver failure illustrates the difference between liver injury and liver dysfunction. Raised alanine aminotransferase and aspartate aminotransferase primarily indicate hepatocellular injury, whereas reduced albumin, impaired coagulation, rising bilirubin and clinical complications provide information about functional capacity, although each marker has limitations. A patient can have substantial liver injury without immediate liver failure, while another can have severe functional impairment with relatively modest enzyme elevations. Similarly, cirrhosis is a structural diagnosis and liver failure is a functional state; cirrhosis can cause liver failure, but liver failure is not synonymous with cirrhosis because acute liver failure can occur without established chronic scarring. These distinctions are important for accurate diagnosis, prognosis and treatment.
The consequences of liver failure extend beyond the liver because hepatic dysfunction affects other organs and physiological systems. Kidney injury may occur through haemodynamic changes, infection or hepatorenal physiology. Brain function may deteriorate because altered hepatic metabolism permits accumulation of substances that influence neuronal function. Immune dysfunction increases susceptibility to bacterial infections, while circulatory changes can cause low systemic vascular resistance and impaired effective blood volume. Severe cases may develop respiratory, cardiovascular and metabolic complications. This multisystem nature explains why advanced liver failure is managed through multidisciplinary hepatology, critical-care, transplantation and sometimes renal support teams. The ultimate treatment objective is either recovery of hepatic function, control of the underlying disease or replacement of irreversibly failed liver function through transplantation.
