Acute liver failure is a severe, rapidly progressing condition in which the liver loses its ability to function, leading to two hallmark complications: abnormal blood clotting (coagulopathy) and brain dysfunction caused by liver failure (hepatic encephalopathy). The condition most commonly results from damage to the liver's functional cells, most often following acetaminophen overdose or certain viral infections. Based on available data, this condition typically presents in infancy, though it can also affect older children and adults. Acute liver failure is relatively uncommon, affecting approximately 1 to 5 per 10,000 births. This summary reflects clinical data available as of May 18, 2026.

The clinical presentation of acute liver failure reflects the sudden, severe loss of liver function across multiple body systems. Early features often include profound fatigue, nausea, vomiting, and jaundice, the yellowing of the skin and whites of the eyes caused by the buildup of bilirubin. As the condition progresses, abnormal bleeding and easy bruising become apparent due to impaired production of clotting factors. Neurological involvement, known as hepatic encephalopathy, may range from mild confusion and behavioral changes to severe disorientation, agitation, and loss of consciousness. Swelling of the abdomen caused by fluid accumulation, as well as low blood sugar, may also occur. Not all individuals experience all features, and severity varies considerably.

Acute liver failure results from rapid, extensive damage to the liver's functional tissue (parenchyma), overwhelming the organ's capacity to regenerate or maintain essential functions. The most common cause is acetaminophen overdose, which can occur following intentional or unintentional ingestion of excessive doses. Viral infections, particularly certain hepatitis viruses, represent another important cause. In a subset of cases, variants in the gene TRMU have been identified as a contributing factor; this gene plays a role in mitochondrial function, and its disruption can impair the liver's energy metabolism. Because acute liver failure can arise from diverse causes, identifying the underlying etiology in each individual is an important part of evaluation. The precise inheritance pattern associated with TRMU-related cases is not fully characterized, and genetic counseling is recommended for families where a genetic contribution is suspected.

Diagnosis of acute liver failure is based on a combination of clinical findings, laboratory investigations, and, when a genetic cause is suspected, molecular testing. Laboratory evaluation typically focuses on markers of liver function and injury, including liver enzyme levels, bilirubin, blood clotting tests (such as prothrombin time), and blood glucose. Assessment of hepatic encephalopathy is a critical part of clinical evaluation. When a genetic etiology is considered, molecular genetic testing for variants in the TRMU gene may be undertaken. Because many features of acute liver failure can overlap with other causes of acute liver injury, thorough evaluation is necessary to identify the underlying cause and guide management. Genetic testing is essential to confirm a genetic contribution and distinguish it from other conditions with similar presentations.

Management of acute liver failure requires urgent, multidisciplinary hospital-based care, often in an intensive care setting. Supportive measures form the foundation of treatment and focus on correcting metabolic disturbances, managing hepatic encephalopathy, preventing and treating complications such as infection and abnormal bleeding, and maintaining organ function. Liver transplantation is a critical intervention for individuals who do not recover with supportive care and may be life-saving. For cases caused by acetaminophen overdose, N-acetylcysteine is an established treatment under investigation as a designated therapy for this condition, though its use and timing depend on individual circumstances. Additional therapies, including bioartificial liver support systems and other experimental approaches, are currently under development. Treatment decisions must be individualized and made in close collaboration with a specialized hepatology and transplant team.

The outlook for acute liver failure depends heavily on the underlying cause, the severity of organ involvement at presentation, and how quickly specialized care is initiated. Outcomes vary considerably: some individuals recover full liver function with supportive care alone, particularly when the cause is identified and addressed promptly, while others experience progressive deterioration requiring liver transplantation. Without timely intervention, the condition can be life-threatening. Transplantation has substantially improved survival for individuals who meet eligibility criteria. For those with an identified genetic cause such as a TRMU variant, the long-term course and recurrence risk may differ and should be discussed with a specialist. The course is variable and depends on individual factors including age, cause, and access to specialized care.

Acute liver failure is an active area of clinical investigation, with several clinical trials currently evaluating new treatment approaches. Research efforts are exploring novel liver support systems, regenerative therapies, and pharmacological interventions aimed at improving survival and reducing the need for transplantation. Investigational approaches include bioartificial liver devices designed to temporarily support liver function, as well as targeted biological therapies. Individuals and families interested in participating in clinical research can search ClinicalTrials.gov or speak with their care team about eligibility for ongoing studies.