Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]
Overview
Liver transplantation remains the ultimate therapy for acute liver failure but medical therapy assists in recovery of liver tissue. It acts like a bridge to transplantation. Treatment mainly depends on the underlying etiologies and the complications arising out of it. Liver support systems help in supporting the patients until the liver recovers or can be used as a bridging aid for transplantation.
Medical Therapy
Goal
- Metabolic abnormalities
- Coagulation defects
- Electrolyte and acid-base disturbances
- Advanced chronic kidney disease
- Hypoglycemia
- Encephalopathy
Treatment strategies
General measures
- Treatment involves admission to hospital; often intensive care unit admission or very close observation are required.
- Supportive treatment with adequate nutrition and, optimization of the fluid balance should be done
- Mechanical ventilation, intubation is indicated for stage 3 or 4 encephalopathy
- Sepsis and infections are common with fulminant liver failure. Though prophylactic antibiotic decreases the risk of infection, but is not routinely recommended as no survival benefits have been proved. Nevertheless, broad coverage with antibiotics is recommended for suspected cases of sepsis.
- Routine administration of steroids for adrenal insufficiency is not recommended.
- H2 receptor blocker and proton pump inhibitors are indicated to prevent and treat stress gastropathy.
- Early transfer to a liver transplantation center should be decided based on patient's clinical status.
2011 AASLD Recommendations : General Measures [1](DO NOT EDIT)
| Class III
|
| 1. Patients with ALF should be hospitalized and monitored frequently, preferably in an ICU.
|
| 2. The precise etiology of ALF should be sought to guide further management decisions.
|
Management of increased intracranial pressure
- Intracranial pressure monitoring in severe encephalopathy and impending cerebral edema should be done with extradural sensors
- The goal should be to maintain the intracranial pressure below 20 mm Hg and the cerebral perfusion pressure above 70 mm Hg.
- Lactulose is indicated in cases of encephalopathy.
- Mannitol, 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes for reducing cerebral edema
- Mannitol should be avoided in patients with advanced chronic kidney diseases.
- Hypernatremia (145-155 mEq/L) through intravenous hypertonic saline infusion to induce hypernatremia may be used to reduce intracranial hypertension.
- Hypothermia (32–34 °C) may reduce intracranial pressure in refractory cases can be tried.
- Other measures like elevation of head end to 30 degrees, hyperventilation and intravenous prostaglandin E1can also be used.
- Short-acting barbiturate, propofol, or i/v indomethacin for refractory intracranial hypertension.
Treatment for specific underlying cause
Acetaminophen or Paracetamol poisoning
- Acetylcysteine for paracetamol poisoning up to 72 hours after ingestion
- It improves cerebral blood flow and increases transplant-free survival in patients with stage 1 or 2 encephalopathy due to hepatic failure of any cause.
- Its treatment can increase prothrombin time giving a false alarm of worsening liver failure.
- 140 mg/kg orally followed by 70 mg/kg orally every 4 hours for an additional 17 doses or
- 150 mg/kg in 5% dextrose intravenously over 15 minutes followed by 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours.
2011 AASLD Recommendations : Acetaminophen Hepatotoxicity [1](DO NOT EDIT)
| Class I
|
| 1. For patients with known or suspected acetaminophen overdose within 4 hours of presentation, give activated charcoal just prior to starting NAC dosing.
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| Class II-1
|
| 1. Begin NAC promptly in all patients where the quantity of acetaminophen ingested, serum drug level or rising aminotransferases indicate impending or evolving liver injury.
|
| Class III
|
| 1. 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.
|
Mushroom poisoning
- Penicillin G - 300,000 to 1 million units/kg/day or
- Silibinin/silymarin/milk thistle (not licensed in the United States)
2011 AASLD Recommendations : Mushroom Poisoning [1](DO NOT EDIT)
| Class III
|
| 1. In ALF patients with known or suspected mushroom poisoning, consider administration of penicillin G and N-acetylcysteine.
|
| 2. Patients with acute liver failure secondary to mushroom poisoning should be listed for transplantation, as this procedure is often the only lifesaving option.
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Drug Induced Hepatoxicity
- Drugs other than acetaminophen rarely cause dose induced toxicity.
- The mechanism of toxicity is mostly due to idiosyncratic toxicity.
- No specific antidotes exist for these idiosyncratic drug reactions.
- Corticosteroids are not indicated unless a drug hypersensitivity(drug rash with eosinophilia and systemic symptoms) syndrome or an autoimmune reaction is suspected.
2011 AASLD Recommendations : Drug Induced Hepatoxicity [1](DO NOT EDIT)
| Class I
|
| 1. N-acetylcysteine may be beneficial for acute liver failure due to drug-induced liver injury.
|
| Class III
|
| 1. 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.
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| 2. Determine ingredients of non-prescription medications whenever possible.
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| 3. In the setting of acute liver failure due to possible drug hepatotoxicity, discontinue all but essential medications.
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Chronic viral hepatitis
- Nucleoside analogs - Fulminant hepatitis B
2011 AASLD Recommendations : Viral Hepatitis [1](DO NOT EDIT)
| Class III
|
| 1. 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.
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| 2. Nucleos(t)ide analogues should be considered for hepatitis B-associated acute liver failure and for prevention of post-transplant recurrence.
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Herpes simplex hepatitis
2011 AASLD Recommendations : Herpes Simplex Hepatitis [1](DO NOT EDIT)
| Class III
|
| 1. 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.
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Wilson disease
2011 AASLD Recommendations : Wilson Disease [1](DO NOT EDIT)
These are the support devices helping in providing some time to help failing liver to recover. These can also be used as a bridge to transplantation. There are two kinds of devices sorbent based artificial system and cell based bio-artificial system. There is no good evidence showing low mortality with their use in acute liver failure[2]. They are not recommended outside of clinical trials as of now.
References
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