Acute Liver Failure

Acute liver failure is rapid onset severe liver injury with synthetic dysfunction (coagulopathy, INR greater than 1.5) and hepatic encephalopathy. It occurs in a patient without pre-existing chronic liver disease, within 26 weeks of the onset of symptoms.

It is subclassified by interval from jaundice to encephalopathy:

• Hyperacute (within 7 days): often paracetamol or viral hepatitis, better prognosis per unit of severity despite dramatic presentation.
• Acute (8 to 28 days).
• Subacute (29 to 26 weeks): often drug induced or seronegative, generally worse prognosis.

Major causes include:

• Paracetamol overdose (leading cause in many high income settings).
• Viral hepatitis (A, B, and E particularly, E notably in pregnancy where it carries high mortality).
• Drug induced liver injury (idiosyncratic reactions, including anti-tuberculous therapy and certain antibiotics).
• Autoimmune hepatitis, and Wilson disease (particularly in younger patients).
• Acute fatty liver of pregnancy and HELLP syndrome.
• Ischemic hepatitis (shock liver), Budd-Chiari syndrome, and Amanita mushroom poisoning.

• Jaundice, coagulopathy manifesting as easy bruising or spontaneous bleeding, and hepatic encephalopathy ranging from subtle confusion and mood change through to coma (see Hepatic Encephalopathy entry for grading).

• Additional features include nausea and vomiting, right upper quadrant discomfort, fetor hepaticus, asterixis, and, as the condition progresses, signs of cerebral edema (papilledema, hypertension, bradycardia, decerebrate posturing) which carries a significant mortality risk and requires urgent recognition.

• Multi-organ involvement is common in severe cases: acute kidney injury (hepatorenal physiology or direct toxic injury), hypoglycemia (impaired gluconeogenesis, requires frequent monitoring), and hemodynamic instability resembling septic shock from systemic inflammatory response.

• Coagulation profile (INR, essential for diagnosis and prognostication).
• LFTs (marked transaminase elevation, though the degree does not correlate well with severity).
• Ammonia (supports encephalopathy diagnosis though levels correlate poorly with grade).
• Glucose (frequent bedside monitoring given hypoglycemia risk).
• U&E and creatinine, arterial blood gas and lactate.
• Paracetamol level in every case regardless of reported history, since accidental or concealed overdose is common and treatable.
• Viral hepatitis serology, autoimmune markers, ceruloplasmin and slit lamp examination for Kayser-Fleischer rings if Wilson disease is suspected, and toxicology screen complete the etiological workup.
• Imaging (ultrasound with Doppler) assesses liver size, texture, and hepatic vein patency to exclude Budd-Chiari syndrome.
• Prognostic scoring, most commonly the King's College Hospital criteria, guides transplant listing decisions and differs by paracetamol versus non-paracetamol etiology.

Differentials include acute on chronic liver failure (decompensation of previously unrecognized cirrhosis, an important distinction since management and prognosis differ substantially) and other causes of encephalopathy (sepsis, intracranial pathology, drug intoxication).

Management is best delivered in a liver unit with ICU capability, ideally with early transfer to a transplant center once the diagnosis is suspected, given how rapidly deterioration can occur.

• N-acetylcysteine is given for paracetamol induced liver failure regardless of time since ingestion, and increasingly used empirically in non-paracetamol acute liver failure given a plausible benefit and low risk.

• Coagulopathy is generally not corrected prophylactically (INR is a prognostic marker that correction would obscure), reserving blood product support for active bleeding or before invasive procedures.

• Hepatic encephalopathy and cerebral edema are managed with head elevation, avoidance of stimulation, mannitol or hypertonic saline for evidence of raised intracranial pressure, and, in some centers, invasive intracranial pressure monitoring in high grade encephalopathy. Hypoglycemia is corrected aggressively with dextrose infusion.

• Renal replacement therapy is used early for evolving acute kidney injury, both for renal support and to assist ammonia clearance.

• Infection is a leading cause of death and should be sought and treated aggressively, with a low threshold for empirical broad spectrum antibiotics given blunted normal inflammatory markers in liver failure.

• Specific antidotes are given where relevant (N-acetylcysteine for paracetamol, penicillin or silibinin for Amanita poisoning, antivirals for HBV related failure).

• Emergency liver transplantation is the definitive treatment for patients meeting poor prognostic criteria who have no contraindication, and survival without transplant is poor once King's College criteria are met.

Referral: immediate discussion with a specialist liver unit or transplant center for any patient with coagulopathy and altered mental status in the context of acute liver injury; this should not be delayed pending full investigation.