Management of Acute Liver Failure

Acute liver failure remains a rare syndrome in the United Kingdom, with approximately 6 cases per million of the population presenting annually. In low- and middle-income countries, the annual incidence is reported to be as high as 60 per million. Acute liver failure is defined as the development of both coagulopathy (INR ≥ 1.5) and hepatic encephalopathy in a patient with acute liver inflammation and no preceding history of chronic liver disease. The leading aetiology of acute liver failure in the UK is drug-induced liver injury, predominantly from paracetamol. Internationally, viral hepatitis, particularly hepatitis E, hepatitis B and hepatitis A, is more common. The occurrence of rarer causes, such as autoimmune hepatitis, Budd Chiari syndrome, pregnancy- related liver disease, malignancy and Wilson’s disease, requires a systematic approach to diagnosis. Indeterminate (or seronegative) acute liver failure, where no aetiology or trigger for the liver inflammation can be identified, is frequently encountered, and more commonly presents as a subacute phenotype. Acute liver failure can be helpfully subclassified into three clinical phenotypes by the time taken for encephalopathy to manifest after the onset of biochemical liver injury, the jaundice-to-encephalopathy time. A short period, ≤ 7 days, is hyperacute liver failure, which commonly progresses to multi-organ failure and the requirement for critical care support. Acute liver failure is defined as when the jaundice-to-encephalopathy time is between 7 and 28 days. Subacute liver failure is a more indolent presentation where a longer period of inflammation results in later onset encephalopathy (between 4 and 12 weeks after the onset of jaundice), often due to a failure of adequate liver regeneration. The severity of liver failure is assessed internationally using several prognostic scoring systems; in the United Kingdom, we most commonly use the modified King’s College Criteria. The overall hospital survival from acute liver failure in the United Kingdom is approximately 69%, with 51 patients having received an emergency liver transplant for acute liver failure in 2024–25. One-year survival for those receiving emergency liver transplant is 91.8%. The short-term transplant-free survival in hyperacute liver failure for those who meet King’s College Criteria predictors of poor prognosis is 33%. Patients with subacute liver failure have a poorer prognosis, and most are likely to die without an emergency liver transplant. Once acute liver failure is recognized, early discussion with a liver failure and liver transplant centre is recommended, and transfer is usually required for patients with progressive coagulopathy, any degree of encephalopathy, significant acute kidney injury, persistent hyperlactataemia or acidaemia. The mainstay of treatment is supportive, with a focus on identifying any cause-specific interventions (such as anti-viral therapy for acute hepatitis B), anticipating and preventing complications of acute liver failure (such as cerebral oedema) and defining those who may have a poor prognosis and should be considered for liver transplantation. Critical care support is targeted to provide optimal cardiovascular support for predominantly vasoplegic shock, respiratory support with lung protective settings, renal replacement therapy and prophylaxis against bacterial and fungal infection. Acetylcysteine is recommended for all aetiologies of acute liver failure for up to 5 days. An increased understanding of the mechanisms of brain injury has led to effective prophylaxis against intracerebral hypertension. High-risk groups for intracerebral hypertension are young patients (<30 years old), females, those with a hyperacute phenotype and those with a lower serum sodium concentration. Prophylaxis is targeted at ammonia control, maintenance of a hyperosmolar blood compartment with hypernatraemia, control of cerebral blood flow and treatment of the systemic inflammatory response. Ammonia is effectively cleared with haemodialysis, and the rate of clearance is linearly related to the dose. Therapeutic plasma exchange for acute liver failure can be an effective therapy, and two randomised controlled trials have shown a survival benefit in patients not suitable for liver transplantation. The real-world experience is more mixed due to the heterogeneity of the population and a reluctance to use therapeutic plasma exchange for all but the sickest patients due to concerns over the potential harms of immunocompromise, transfusion-associated lung injury and cardiac overload. Liver transplantation is an established treatment, associated with good long-term survival, for patients meeting poor prognostic criteria. The use of auxiliary transplantation has helped to reduce the long-term burden of immunosuppression for selected patients with acute liver failure. Future research is directed either to developing more effective bridging therapies, such as encapsulated hepatocyte microbeads, or extracorporeal liver support devices that can provide time for native liver regeneration. References 1. Glover F, Saha R, Hogan BJ. Hepatic failure. In, Oh’s Intensive Care Manual (9th Edition). Ed Handy JM, Venkatesh B. 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