Acute Liver Failure
GENERAL PRINCIPLES
ALF is a condition that includes evidence of a combination of coagulation abnormalities and any degree of mental alteration (encephalopathy) in a patient without preexisting liver disease and with an illness of lt;26 weeks in duration.
In 20% of cases, no clear cause is identified. Acetaminophen hepatotoxicity and viral hepatitis are the most common causes of ALF. Other causes include AIH, drug and toxin exposure, ischemia, acute fatty liver of pregnancy, WD, and Budd-Chiari syndrome.
Acute inflammation with varying degrees of necrosis and collapse of the liver's architectural framework are the typical histologic changes seen in ALF.
DIAGNOSIS
Clinical Presentation
Patients often present with mild to severe mental status changes in the setting of moderate to severe acute hepatitis and coagulopathy.
Patients may develop cardiovascular collapse, acute renal failure, cerebral edema, and sepsis.
Diagnostic Testing
Aminotransferases are typically elevated and, in many cases, are gt;1000 IU/L.
INR gt;1.5 that does not correct with the administration of vitamin K is characteristic.
Workup to determine the etiology of ALF should include acute viral hepatitis panel, serum drug screen (including acetaminophen level), ceruloplasmin, AIH serologies, and pregnancy test.
Right upper quadrant ultrasound with Doppler should be obtained to evaluate obstruction of hepatic venous inflow or outflow.
CT of the head may be obtained to evaluate and track progression of cerebral edema; however, the radiologic findings may lag behind its development and do not substitute for serial bedside assessments of neurologic status.
Liver biopsy is seldom used to establish etiology or prognosis. Given the presence of coagulopathy, a transjugular approach to liver biopsy should be attempted if necessary.
TREATMENT
Supportive therapy (quiet dark room, avoid patient stimulation, maintain head of bed elevation to 30 degrees) in the intensive care unit setting with liver transplant capabilities is essential.
Precipitating factors, such as infection, should be identified and treated. Blood glucose, electrolytes, acid-base balance, coagulation parameters, and fluid status should be serially monitored.
Sedatives should be avoided to appropriately gauge the patient's mental status.
NAC may be used in cases of ALF in which acetaminophen ingestion is suspected or when circumstances surrounding admission is inadequate. NAC also appears to improve spontaneous survival when given during early hepatic encephalopathy stages (grades I and II), even in the setting of nonacetaminophen ALF.27
Fresh frozen plasma and the use of recombinant activated factor VIIa should only be considered in the setting of active bleeding or when invasive procedures are required.
Cerebral edema and intracranial hypertension are related to the severity of encephalopathy. In patients with grade III or IV encephalopathy, intracranial pressure monitoring may be considered if local expertise is available (intracranial pressure should be maintained below 20-25 mm Hg and cerebral perfusion pressure should be maintained above 50-60 mm Hg). Management of cerebral edema, when identified by CT imaging, includes intubation with sedation to avoid overstimulation, elevation of the head of the bed, use of mannitol (0.5-1 g/kg), and/or use of hypertonic saline (30% hypertonic saline at a rate of 5-20 mL/h to maintain a serum sodium of 145-155 mmol/L). Lactulose is not indicated for encephalopathy in this setting. Its use may result in increased bowel gas that can interfere with the surgical approach for liver transplantation.28
Liver transplantation should be urgently considered in cases of severe ALF. Poor prognostic indicators in acetaminophen-induced ALF include arterial pH lt; 7.3, INR gt;6.5, creatinine gt;3.4 mg/dL, and encephalopathy grades III through IV (King's College Criteria).
OUTCOME AND PROGNOSIS
In the US, 45% of adults with ALF have a spontaneous recovery, 25% undergo liver transplantation, and 30% die without liver transplantation.29
Death often results from progressive liver failure, GI bleeding, cerebral edema, sepsis, or arrhythmia.
A rapid decline in aminotransferases correlates poorly with prognosis and does not always indicate an improved response to therapy.