Emergent Care / Stabilization:
Patients with severe encephalopathy or significant upper gastrointestinal (GI) bleeding may require emergent airway management.

Provide volume resuscitation and vasopressor support for patients with hemodynamic instability.

Acute liver failure patients can develop increased intracranial pressure. Consider neuroimaging and early neurosurgical consultation, particularly if abnormal neurologic findings (other than altered mental status), are present.

Administer N-acetyl cysteine if there is any clinical concern for acetaminophen toxicity.

Early consultation and potential transfer to a liver transplant center is recommended.

Diagnosis Overview:
Acute liver failure is characterized by a rapid deterioration of liver function with an associated alteration in mental status (hepatic encephalopathy) and coagulopathy. The condition can result from damage to the liver parenchyma from a wide range of etiologies, including drugs or other toxins (acetaminophen most commonly), viral infections, and hypotension with subsequent fulminant hepatitis from septic shock (shock liver), among others. Of note, acute liver failure only occurs in the absence of prior liver disease; worsening of underlying liver disease is more accurately defined as acute decompensation of cirrhosis or acute-on-chronic liver failure.

Acute liver failure can occur at any age. Detailed demographics of acute liver failure are difficult to define, as different etiologies (viral, pregnancy-induced, septic shock, drug-induced) are seen in widely different ages and subsets of the population.

Initial signs and symptoms are frequently nonspecific, including fatigue, lethargy, anorexia, nausea, and vomiting. As the condition progresses, patients may develop jaundice, abdominal pain (often in the right upper quadrant), abdominal distension, hepatomegaly, ascites, edema, and mental status changes. Infants may initially present with irritability, sleep disturbance, hyperbilirubinemia, and failure to thrive. A life-threatening condition, acute liver failure can lead rapidly to hepatic encephalopathy, cerebral edema, GI bleeding, infection, multiorgan failure, and ultimately, death.

Determining the etiology of liver failure will guide therapy. Assess for important risk factors, including a history of intravenous (IV) drug use or intranasal cocaine use, occupations that put one at risk for exposure to blood or body fluids, receiving blood transfusions, being on hemodialysis, imprisonment, travel to endemic hepatitis areas, current or history of heavy alcohol use, use of hepatotoxic medications, and concomitant critical illness.

In pregnant patients presenting with acute liver failure, acute fatty liver of pregnancy and HELLP syndrome (hemolysis, elevated liver function tests, low platelets) should be considered as etiologies. Acute fatty liver of pregnancy is rare, occurring in approximately 1 / 20 000 deliveries and presents with abdominal pain, nausea and emesis, and jaundice. Primigravida women, women with multifetal pregnancy, carrying a male fetus, and women with low body mass index are at higher risk of developing acute fatty liver of pregnancy. The diagnosis is primarily clinical, distinguished from HELLP syndrome due to the absence of hemolysis and more evidence of synthetic liver dysfunction (elevated international normalization ratio [INR], elevated bilirubin), although a liver biopsy can be confirmatory by demonstrating microvesicular fatty infiltration in the hepatocytes with minimal necrosis or inflammation. Treatment requires supportive care and prompt delivery of the baby.

Pediatric patients with hepatitis of unknown etiology: A 2022 outbreak of severe hepatitis in children in several countries, with the majority in Great Britain, has still not been connected to an identifiable cause. Common viral hepatitis agents (hepatitis viruses A-E) were screened for and ruled out. The majority of affected children were found to be positive for adenovirus serotype 41 (ad-41), but there has been no clear establishment of a link between adenovirus and acute hepatitis. Further studies are needed to continue investigating possible causes. Signs and symptoms include dark urine; jaundice; scleral icterus; light-colored stools; loss of appetite, abdominal pain, nausea, diarrhea and vomiting, and joint pain. The US Centers for Disease Control and Prevention (CDC) has requested that physicians consider adenovirus testing for pediatric patients with hepatitis of unknown etiology and report any possible cases of hepatitis of unknown origin to the CDC and state public health authorities. The CDC also recommends testing for past or present SARS-CoV-2 infection in children with acute hepatitis, although the possible association is uncertain and under investigation. Pediatric acute hepatitis of unknown origin has been seen at increasing rates since the start of the COVID-19 pandemic but has not yet been studied sufficiently to postulate a connection. There is some speculation, however, that coinfection with adenovirus and SARS-CoV-2 may play a role. See also adenovirus infection.

Related topic: drug-induced hepatotoxicity