Last updated March 15, 2022

Acute Liver Failure

Recommendations

Diagnosis and Initial Evaluation

1. Patients with ALF should be hospitalized and monitored frequently, preferably in an ICU. (III, )
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2. Contact with a transplant center and plans to transfer appropriate patients with ALF should be initiated early in the evaluation process.. (III, )
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3. The precise etiology of ALF should be sought to guide further management decisions. (III, )
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Determining Etiologies and Specific Therapies

4. For patients with known or suspected acetaminophen overdose within 4 hours of presentation, give activated charcoal just prior to starting NAC dosing. (I, )
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5. Begin NAC promptly in all patients where the quantity of acetaminophen ingested, serum drug level or rising aminotransferases indicate impending or evolving liver injury. (II-1, )
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6. NAC may be used in cases of acute liver failure in which acetaminophen ingestion is possible or when knowledge of circumstances surrounding admission is inadequate but aminotransferases suggest acetaminophen poisoning. (III, )
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7. In ALF patients with known or suspected mushroom poisoning, consider administration of penicillin G and N-acetylcysteine. (III, )
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8. Patients with acute liver failure secondary to mushroom poisoning should be listed for transplantation, as this procedure is often the only lifesaving option. (III, )
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9. Obtain details (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year. (III, )
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10. Determine ingredients of non-prescription medications whenever possible. (III, )
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11. In the setting of acute liver failure due to possible drug hepatotoxicity, discontinue all but essential medications. (III, )
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12. N-acetylcysteine may be beneficial for acute liver failure due to drug-induced liver injury. (I, )
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13. Viral hepatitis A- (and E-) related acute liver failure must be treated with supportive care as no virus-specific treatment has proven to be effective. (III, )
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14. Nucleos(t)ide analogues should be considered for hepatitis B-associated acute liver failure and for prevention of post-transplant recurrence. (III, )
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15. Patients with known or suspected herpes virus or varicella zoster as the cause of acute liver failure should be treated with acyclovir (5-10 mg/kg IV every 8 hours) and may be considered for transplantation. (III, )
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16. To exclude Wilson disease one should obtain ceruloplasmin, serum and urinary copper levels, slit lamp examination for Kayser-Fleischer rings, hepatic copper levels when liver biopsy is feasible, and total bilirubin/alkaline phosphatase ratio. (III, )
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17. Patients in whom Wilson disease is the likely cause of acute liver failure must be promptly considered for liver transplantation. (III, )
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18. Liver biopsy is recommended when autoimmune hepatitis is suspected as the cause of acute liver failure, and autoantibodies are negative. (III, )
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19. Patients with coagulopathy and mild hepatic encephalopathy due to autoimmune hepatitis may be considered for corticosteroid treatment (prednisone, 40-60 mg/day). (III, )
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20. Patients with autoimmune hepatitis should be considered for transplantation even while corticosteroids are being administered. (III, )
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21. For acute fatty liver of pregnancy or the HELLP syndrome, expeditious delivery of the infant is recommended. Transplantation may need to be considered if hepatic failure does not resolve quickly following delivery. (III, )
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22. In ALF patients with evidence of ischemic injury, cardiovascular support is the treatment of choice. (III, )
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23. Hepatic vein thrombosis with acute hepatic failure is an indication for liver transplantation, provided underlying malignancy is excluded. (II-3, )
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24. In patients with acute liver failure who have a previous cancer history or massive hepatomegaly, consider underlying malignancy and obtain imaging and liver biopsy to confirm or exclude the diagnosis. (III, )
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25. If the etiological diagnosis remains elusive after extensive initial evaluation, liver biopsy may be appropriate to attempt to identify a specific etiology that might influence treatment strategy. (III, )
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Central Nervous System

26. In early stages of encephalopathy, lactulose may be used either orally or rectally to effect a bowel purge, but should not be administered to the point of diarrhea, and may interfere with the surgical field by increasing bowel distention during liver transplantation. (III, )
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27. Patients who progress to high-grade hepatic encephalopathy (grade III or IV) should undergo endotracheal intubation. (III, )
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28. Seizure activity should be treated with phenytoin and benzodiazepines with short half-lives. Prophylactic phenytoin is not recommended. (III, )
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29. Intracranial pressure monitoring is recommended in ALF patients with high grade hepatic encephalopathy, in centers with expertise in ICP monitoring, in patients awaiting and undergoing liver transplantation. (III, )
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30. In the absence of ICP monitoring, frequent (hourly) neurological evaluation is recommended to identify early evidence of intracranial hypertension. (III, )
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31. In the event of intracranial hypertension, a mannitol bolus (0.5-1.0 gm/kg body weight) is recommended as first-line therapy; however, the prophylactic administration of mannitol is not recommended. (II-2, )
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32. In ALF patients at highest risk for cerebral edema (serum ammonia > 150 lM, grade 3/4 hepatic encephalopathy, acute renal failure, requiring vasopressors to maintain MAP), the prophylactic induction of hypernatremia with hypertonic saline to a sodium level of 145-155 mEq/L is recommended. (I, )
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33. Short-acting barbiturates and the induction of hypothermia to a core body temperature of 34- 35C° may be considered for intracranial hypertension refractory to osmotic agents as a bridge to liver transplantation. (II-3, )
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34. Corticosteroids should not be used to control elevated ICP in patients with ALF. (I, )
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35. Periodic surveillance cultures are recommended to detect bacterial and fungal pathogens as early as possible. Antibiotic treatment should be initiated promptly according to surveillance culture results at the earliest sign of active infection or deterioration (progression to high grade hepatic encephalopathy or elements of the SIRS). (III, )
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36. Prophylactic antibiotics and antifungals have not been shown to improve overall outcomes in ALF and therefore cannot be advocated in all patients, particularly those with mild hepatic encephalopathy. (III, )
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37. Replacement therapy for thrombocytopenia and/or prolonged prothrombin time is recommended only in the setting of hemorrhage or prior to invasive procedures. (III, )
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38. Patients with ALF in the ICU should receive prophylaxis with H2 blocking agents or proton pump inhibitors (or sucralfate as a second-line agent) for acid-related gastrointestinal bleeding associated with stress. (I, )
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Hemodynamics and Renal Failure

39. Fluid resuscitation and maintenance of adequate intravascular volume are recommended on presentation in patients with ALF. The initial treatment of hypotension should be with intravenous normal saline. (III, )
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40. If dialysis support is needed for acute renal failure, it is recommended that a continuous mode rather than an intermittent mode be used. (I, )
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41. Pulmonary artery catheterization is rarely necessary in patients with ALF and is associated with significant morbidity. Instead, appropriate volume status should be ensured with a volume challenge.. (III, )
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42. Systemic vasopressor support with agents such as norepinephrine should be administered in volume-refractory hypotension or to ensure adequate CPP. Vasopressin or terlipressin can be added to norepinephrine in norepinephrine-refractory cases, but should be used cautiously in severely encephalopathic patients with intracranial hypertension. (II-1, )
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43. Goals of circulatory support in patients with ALF are a MAP ≥75 mmHg and CPP 60-80 mmHg. (II-1, )
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Metabolic Concerns

44. Metabolic homeostasis must be carefully maintained in ALF patients. Overall nutritional status as well as glucose, phosphate, potassium and magnesium levels should be monitored frequently, with expeditious correction of derangements. (III, )
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Prognosis and Transplantation

45. Currently available prognostic scoring systems do not adequately predict outcome and determine candidacy for liver transplantation. Reliance entirely upon these guidelines is thus not recommended. (III, )
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46. Urgent hepatic transplantation is indicated in acute liver failure where prognostic indicators suggest a high likelihood of death. (II-3, )
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47. Living donor or auxiliary liver transplantation may be considered in the setting of limited organ supply, but its use remains controversial. (II-3, )
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48. Currently available liver support systems are not recommended outside of clinical trials; their future in the management of acute liver failure remains unclear.

(II-1, )
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Recommendation Grading

Overview

Title

Acute Liver Failure

Authoring Organization

Publication Month/Year

February 1, 2012

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To facilitate proper and high level patient care for patients with acute liver failure

Target Patient Population

Patients with acute liver failure

Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Operating and recovery room, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Management, Treatment

Diseases/Conditions (MeSH)

D008107 - Liver Diseases, D017114 - Liver Failure, Acute, D017093 - Liver Failure, D006505 - Hepatitis, D016031 - Liver Transplantation, D008099 - Liver, D019934 - International Normalized Ratio

Keywords

acute liver failure, hepatitis

Source Citation

DOI 10.1002/hep.25551