Management of Acute Liver Failure
A. Initial Evaluation and Triage
Every patient with acute hepatocellular necrosis can potentially progress to ALF. Drug ingestion history should be obtained to include prescription medications, herbal remedies, over‑the‑counter medications, and recretional drugs. Confounding conditions, such as alcohol use, malnutrition, and drug–drug interactions, must be considered. Past medical history should also include a search for signs, symptoms, and risk factors for chronic liver diseases. A detailed psychiatric history may provide clues about a possible surreptitious ingestion of hepatotoxins, particularly acetaminophen. Initial laboratories should include tests to assess the degree of physiologic dysfunction, risk of mortality, and potential need for liver transplantation. Patients in whom the initial prothrombin time is more than 4 to 5 seconds prolonged should be admitted to the hospital for observation; the clinician should not be lulled into a false sense of security by a normal mental status in the presence of signifcant coagulopathy. Furthermore, patients with altered mental status, hemodynamic compromise, renal insuffciency, decreased oxygenation, acidosis, or hypoglycemia should be admitted to an intensive care facility, and the patient should be discussed with the nearest liver transplant center. Whether to proceed with liver transplantation evaluation remains perhaps the most important decision in the initial evaluation of a patient with ALF. Patients with grade 2 or higher encephalopathy should be evaluated unless contrain‑dications exist. In subjects with lesser degrees of encephalopathy, profound coagulopathy (prothrombin time >50 seconds) or acidosis (pH <7.3) should also lead to early consideration for listing for transplant. Older subjects, those with idiosyncratic drug‑induced ALF and patients with a subacute presentation, should be evaluated relatively early in the course of ALF in consideratio n of their poor prognosis for spontaneous recovery. B. Therapies for Liver Injury 1. N‑acetylcysteine (NAC) for Acetaminophen Overdose. The use of an antidote may decrease hepatic injury and reverse ALF in specifc circumstances. N‑acetylcysteine (NAC) remains the treatment of choice for acetaminophen overdose, and in
theory, may protect the liver from other toxins that cause hepatotoxicity by generating free radicals, such as carbon tetrachloride or trichlorethylene. 2. N‑acetylcysteine (NAC) for Non‑APAP ALF The ALF Study Group trial concluded that IV NAC improved spontaneous (nontransplanted) survival compared with a placebo, but only in patients with grade 1 or 2 hepatic encephalopathy. Suspected mushroom poisoning should be treated initially with ipecac and charcoal to decrease the Amanita toxin load, if the ingestion has occurred recently (within 30 minutes to a few hours). NAC is also frequently advocated, although with scant supporting data. 3. Other Etiology‑Specifc Therapies A combination of penicillin (300,000 to 1,000,000 units/kg/day, or 250 mg/kg/day IV) and silibinin (20 to 50 mg/kg/day IV) have been used as a specifc antidote in those with evidence of liver injury due to Amanita poisoning. These agents are hypothesized to interrupt the enterohepatic circulation of toxins and also to compete at the hepatocyte membrane for transmembrane transport. Due to the rarity of this cause of ALF, the benefts of this regimen remain unproven. The use of corticosteroids for autoimmune ALF remains controversial but merits consideration in patients with early stage hepatic encephalopathy. 4. Management of Fluids, Electrolytes, and Acid-Base Abnormalities Fluid and electrolyte abnormalities occur frequently in patients with ALF.. Management requires isotonic intravenous fuid such as 0.9% saline (sodium 155 mmol/L) with or without dextrose. The target serum sodium concentration is 145 to 155 mmol/L, which has been associated with a reduced incidence of cerebral edema. 5. Management of Nutrition ALF is a catabolic state characterized by negative nitrogen balance, muscle wasting, and aminoaciduria. While the clinical value of nutritional support in ALF has not been carefully studied, protein‑calorie malnutrition adversely affects the immune system, thereby increasing susceptibility to infections, and impairs wound healing, suggesting that repletion may decrease the risk of infection and improve the outcome of liver transplantation, respectively.