Diagnosis and Early Evaluation 2.1 All patients with ALF should be hospitalized and closely monitored for their condition, preferably in an intensive care (ICU) unit. (III) 2.2 Transplant centers should be contacted early in the evaluation process and a plan for transferring patients with ALF who are indicated for transplantation should be developed. (III) 2.3 Aggressively search for the exact etiology of ALF to guide the development of further treatment strategies. (III) Hepatotoxicity of acetaminophen Xiaofeng Liu, Department of Gastroenterology, General Hospital of Jinan Military Region 2.4 Patients with definite and suspected acetaminophen overdose should be given activated charcoal therapy within 4 hours of ingestion of the drug before administration of N-acetylcysteine (NAC) (I). 2.5 Patients with acetaminophen overdose should be rapidly administered NAC, and monitoring of serum drug concentrations and elevated transaminases are suggestive of impending or established hepatic damage (II-1). 2.6 NAC may also be indicated in patients with ALF suspected to be due to acetaminophen ingestion or in patients with ALF in whom the history of acetaminophen ingestion is unclear, but in whom aminotransferase changes are suggestive of acetaminophen toxicity (III). Acute Liver Failure Not Due to Acetaminophen 2.7 Penicillin G and N-acetylcysteine (III) should be indicated in those with confirmed or suspected muscarinic toxicity. 2.8 Persons with ALF secondary to muscarinic intoxication should be listed for liver transplantation, which may be the only way to save the lives of such patients (III). Drug Induced Liver Injury (DILI) 2.9 Details (including time of initiation, dosage, time of last dose) of relevant prescription drugs, over-the-counter medications, herbs, and food additives taken by the patient in the past few years should be obtained (III). 2.10 Identify the composition of over-the-counter medicines wherever possible (III). 2.11 In ALF that may be due to hepatotoxicity of medications, discontinue all but essential medications (III). 2.12 N-acetylcysteine (NAC) is beneficial in drug-induced ALF (I). Viral Hepatitis 2.13 Supportive therapy should be intensified for ALF due to hepatitis A virus and hepatitis E virus, as there are no specific antiviral regimens for these viruses (III). 2.14 Nucleoside (acid) analogs should be considered for hepatitis B virus-associated ALF, which may also prevent relapse after transplantation (III). 2.15 In persons with confirmed or suspected ALF due to herpes simplex virus or varicella-zoster virus infection, acyclovir (5 to 10 mg/kg, IV, 1/8 h) should be administered, and liver transplantation should be considered (III). Wilson’s disease 2.16 Copper blue protein, urine and serum copper level testing, slit lamp examination of the Kayser-Fleischer ring, and testing of hepatic copper levels after liver biopsy can rule out Wilson’s disease (hepatomegaly), and attention should also be paid to monitoring the total bilirubin to alkaline phosphatase ratio (III). 2.17 Liver transplantation should be considered as soon as possible in those with suspected Wilson’s disease causing ALF (III). Autoimmune hepatitis 2.18 Liver biopsy is recommended when autoimmune hepatitis is suspected to be the cause of ALF and autoantibodies are negative (III). 2.19 Hormonal therapy (prednisone 40-60 mg/d) should be considered for coagulation disorders and mild hepatic encephalopathy due to autoimmune hepatitis (III) 2.20 Liver transplantation should be considered in patients with autoimmune hepatitis, even during glucocorticoid therapy (III). Acute fatty liver/HELLP syndrome in pregnancy 2.21 ALF due to acute fatty liver and HELLP syndrome (hemolysis combined with high liver enzymes and low platelet syndrome) in pregnancy suggests termination of pregnancy as soon as possible, and liver transplantation should be considered if termination is not effective (III). Acute Ischemic Injury 2.22 In ALF due to ischemia, cardiovascular support is a treatment option (III). Budd-Chiari syndrome 2.23 Hepatic vein thrombosis with ALF is an indication for liver transplantation after excluding the possibility of malignancy (II-3). Malignant Infiltration 2.24 ALF with a previous history of neoplasia or in the presence of significant hepatomegaly where malignancy is suspected should undergo imaging and hepatic aspiration biopsy to confirm or exclude the diagnosis (III). Unspecified etiology 2.25 In cases where the etiology cannot be determined after a comprehensive evaluation, liver biopsy should be considered to clarify the etiology to guide the development of a therapeutic regimen (III). Central Nervous System 2.26 In the early stages of hepatic encephalopathy, lactulose may be administered orally or rectally to cleanse the bowel, but it should not be administered in the presence of diarrhea and may result in intestinal distention that may interfere with liver transplantation (III). 2.27 Tracheal intubation should be performed to maintain an open airway in those with progression to high-grade hepatic encephalopathy (stage III or IV) (III). 2.28 Phenytoin or benzodiazepines with short half-lives may be used for active seizures. However, prophylactic application of phenytoin is not recommended (III). 2.29 Intracranial pressure (ICP) monitoring is recommended for persons with high-grade hepatic encephalopathy and those awaiting or undergoing liver transplantation (III). 2.30 In the absence of intracranial pressure monitoring, frequent (hourly) neurologic assessment should be performed for early identification of intracranial hypertension (III). 2.31 Once the presence of intracranial hypertension is established, rapid push mannitol (0.5 to 1.0 g/kg) is recommended as first-line treatment; however, prophylactic application of mannitol is not advocated (II-2). 2.32 In patients with ALF who are at high risk for cerebral edema (blood ammonia >150 μmol, III or IV hepatic encephalopathy, acute renal failure, and need for vasopressor analogs to maintain mean arterial pressure), prophylactic induction of hypernatremia with the application of hypertonic saline (145 to 155 mEq/L) is recommended (I). 2.33 Short-acting barbiturates and induction of hypothermia to bring the central body temperature to 34 to 35°C can be used in patients with refractory intracranial hypertension who have failed to respond to osmotic medications, thereby preparing them for liver transplantation (II-3). 2.34 The application of glucocorticoids to control increased intracranial pressure is not recommended in patients with ALF (I). Infections 2.35 Culture tests for bacteria and fungi should be performed as early and regularly as possible. Antibiotics should be applied as soon as possible on the basis of bacterial culture results at the earliest signs of active infection and progression [progression to high-grade hepatic encephalopathy or systemic inflammatory response syndrome (SIRS)] (III). 2.36 Prophylactic application of antibiotics and antifungals does not improve the prognosis of ALF and is therefore not recommended for all patients, especially those with mild hepatic encephalopathy (III). Coagulation disorders 2.37 In persons with thrombocytopenia and prolonged prothrombin time, substitution therapy is recommended only in the setting of bleeding or before invasive procedures (III). Bleeding 2.38 Patients with ALF in the ICU should be prophylactically administered H2 receptor antagonists or proton pump inhibitors (aluminum thioglycollate may be used as a second-line agent) to prevent acid-associated gastrointestinal bleeding in stressful conditions (I). Hemodynamics and Renal Failure 2.39 Fluid resuscitation and maintenance of adequate blood volume are recommended for those with ALF. Initial treatment of hypotension may include intravenous saline (III). 2.40 If dialysis is required in persons with acute renal failure, a continuous dialysis pattern is recommended over an intermittent dialysis pattern (I). 2.41 Pulmonary artery catheterization (PAC) is rarely used in persons with ALF and should be substituted to ensure an appropriate effective circulatory status (III). 2.42 For dilation-refractory hypotension or to maintain adequate cerebral perfusion pressure (CPP), systemic vasopressor supportive therapy such as injections of drugs such as norepinephrine may be indicated. Vasopressin or terlipressin may be added in cases where norepinephrine therapy is not effective, but should be used with caution in patients with severe hepatic encephalopathy in the presence of intracranial hypertension (II-1). 2.43 The goals of circulatory support in ALF are a mean arterial pressure (MAP) ≥75 mmHg and a cerebral perfusion pressure (CPP) of 60 to 80 mmHg.(II) Metabolic-Related Problems 2.44 A state of metabolic homeostasis must be maintained in the patient with ALF, and the systemic nutritional status as well as glucose metabolism, phosphate, potassium, and magnesium levels should be monitored from time to time and disorders corrected rapidly. (III) Prognosis 2.45 Currently popular prognostic scoring systems are inadequate for predicting prognosis and identifying liver transplant candidates, and complete reliance on these guidelines is not recommended (III). Transplantation 2.46 Patients with ALF whose prognostic indicators suggest a high risk of mortality are indicative of urgent liver transplantation (II-3). 2.47 Living donor (living donor) or auxiliary liver transplantation (auxiliary liver transplantation) may be considered in the setting of severe donor shortage, but this is currently controversial (II-3). LIVER SUPPORT SYSTEMS 2.48 The application of currently used liver support systems is not recommended, except for clinical validation, and the future of their use for ALF disposition remains unclear (II-1).