Acute Liver Failure

Posted by • December 27th, 2013

Acute liver failure is a rare but life-threatening critical illness requiring intensive care. The latest article in our Critical Care Medicine series reviews common causes, diagnostic approaches, and therapeutic interventions.

Acute liver failure is a rare but life-threatening critical illness that occurs most often in patients who do not have preexisting liver disease. With an incidence of fewer than 10 cases per million persons per year in the developed world, acute liver failure is seen most commonly in previously healthy adults in their 30s and presents unique challenges in clinical management.

Clinical Pearls

What viral infections are most often associated with acute liver failure globally? 

Globally, hepatitis A and E infections are probably responsible for the majority of cases of acute liver failure, with rates of death of more than 50% reported from the developing world. Acute liver failure may also occur after hepatitis B infection, which is a common cause in some Asian and Mediterranean countries. Particularly poor survival has been seen in patients with reactivation of previously stable subclinical infection with the hepatitis B virus without established chronic liver disease. This scenario is most common in patients with treatment-induced immunosuppression during or after therapy for cancer. The identification of at-risk patients and the use of antiviral prophylaxis before the initiation of chemotherapy,  immunotherapy, or glucocorticoid therapy are effective in prevention.  Other rare viral causes of acute liver failure include herpes simplex virus, cytomegalovirus, Epstein-Barr virus, and parvoviruses.

What are the features associated with acetaminophen-induced hepatotoxicity and what affects prognosis?

Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure in the United States. It may also be idiosyncratic, unpredictable, and probably independent of dose.  Although acute liver failure after acetaminophen ingestion can occur after consumption of a single large dose, the risk of death is greatest with substantial drug ingestion staggered over hours or days rather than at a single time point. Acute liver failure is more common with late presentation to medical attention because of unintentional rather than deliberate self-poisoning. Malnourished or alcoholic patients are at increased risk. In patients with severe acetaminophen poisoning, the interval between drug ingestion and treatment with acetylcysteine is closely related to the outcome.

Morning Report Questions

Q: What are the principles of initial care in acute liver failure? 

A: Early restoration of intravascular volume and systemic perfusion may prevent or mitigate the severity of organ failure. Acetylcysteine has complex antioxidant and immunologic effects that may benefit patients with non-acetaminophen-related acute liver failure. Encephalopathy may progress rapidly, particularly in patients with hyperacute disease. For patients with progression to agitation or coma, the authors recommend early endotracheal intubation and sedation for airway control in order to facilitate general care, control oxygen and carbon dioxide levels, and prevent aspiration pneumonitis, although practice varies according to center. Overt bleeding is uncommon in patients with acute liver failure and reflects a defect in hemostatic balance. In most cases, the loss of hepatic synthesis of procoagulant factors is paralleled by the loss of hepatically derived anticoagulants. Functional testing indicates no major bleeding tendency and may even indicate the presence of a procoagulant state. Since serial evaluation of laboratory coagulation variables is central to prognostic evaluation, the administration of coagulation factors should be avoided, except when needed to treat bleeding or before invasive procedures.

Table 1. Common Management Issues and Condition-Specific Elements of Care in Acute Liver Failure. 

Q: What are the necessary components of neurologic care in patients with acute liver failure?  

A: Neurologic care focuses on the prevention of infection, the maintenance of stable cerebral perfusion, and the control of circulating ammonia and its cerebral metabolism. The drug l-ornithine-l-aspartate enhances ammonia detoxification to glutamine in muscle. However, in a large, randomized, controlled trial, the drug did not lower circulating ammonia levels, reduce the severity of encephalopathy, or improve survival rates among patients with acute liver failure. In patients with established encephalopathy, treatment is focused on minimizing the risk of intracranial hypertension by lowering cerebral ammonia uptake and metabolism through the use of sedation and prophylactic osmotherapy. In a randomized, controlled trial involving patients with high-grade encephalopathy, treatment with intravenous hypertonic saline solution delayed the onset of intracranial hypertension. Treatments that are used in chronic liver disease may be inappropriate in acute liver failure. In particular, the role of neomycin, rifaxamin, and other nonabsorbable antibiotics is unclear, and treatment with lactulose is potentially deleterious.

6 Responses to “Acute Liver Failure”

  1. John Kevin Griffin says:

    Acetaminophen-induced hepatoxicity secondary to CYP2D6 genetic mutation in 10 percent of population due to inability to metabolize the drug ie poor metabolizers.

  2. Mohammed O Skloua says:

    Big thanks.. nice info. Keep it up


  3. Mohammad says:

    Very nice . Thanks

  4. Kim Setser says:

    Wondering – do you have a link to any articles regarding the use of lactulose being harmful in acute liver failure? I’ve seen a few statements here and other places, but no references.


  5. Good article but still requires researcb

  6. Ali Aldahbali says:

    Acute Liver Failure may be as a result of super-parasite as Ascaridiosis, especially in patients from poor countries and low hyghenic.