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Critical Care Alert: Role of N-Acetylcysteine in Non-acetaminophen-related Acute Liver Failure

NAC is well known to emergency medicine physicians as the antidote in acute acetaminophen ingestion. The scope of use for this medication beyond that is often not considered, such as in other etiologies of acute liver failure like viral hepatitis, infection, autoimmune, etc. As demonstrated by this meta-analysis, the data is difficult to come by, however, as more comes to light, the signal within suggests NAC has more to offer than just an antidote to acute liver failure in the setting of acetaminophen overdose.

Other causes of acute liver failure are inevitably going to present in the emergency department and acknowledging that NAC likely has a place in the care of these patients is…

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Featured

 Tox in The Land: Toxicologic Causes of Acute Liver Failure

When in doubt, NAC.

 Unraveling the mysteries behind America’s No. 1 cause of acute liver failure

“Acetaminophen actually dwarfs by three times the number of liver-injury deaths related to all prescription drugs – which is kind of bizarre because it’s over-the-counter. It’s readily available in hundreds of tablets at a time.”

Articles of Interest

Acute Liver Failure

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.

Acute Liver Failure (ALF)

The greatest life threat is often acute hepatic encephalopathy, which is frequently associated with increased intracranial pressure and herniation. This is far more dangerous than hepatic encephalopathy seen in chronic cirrhosis (which isn't associated with cerebral edema or herniation).

Acute Liver Failure Case

There are several case reports for alternative treatments to acute hepatic encephalopathy discussing the use of sodium benzoate, a common food preservative. It is also used as long-term treatment in urea-cycle disorders.

Acute Liver Failure: Evidence-Based Evaluation and Management

Acute liver failure is the clinical manifestation of sudden and severe hepatic injury, and has a variety of underlying etiologies, including drug toxicity, viral infections, autoimmune and genetic disorders, thrombosis, malignancy, heat injury, and ischemia. Additionally, metabolic disorders like Wilson disease (WD), HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, acute fatty liver of pregnancy, Reye’s syndrome, galactosemia, hereditary fructose intolerance, hemochromatosis, α1-antitrypsin deficiency and tyrosinemia may also cause ALF.

Acute-on-chronic Liver Failure: An Entity Still in Search of Itself?

The development of liver failure in a patient with cirrhosis represents a decisive time point in terms of medical management and of prognosis since this condition is frequently associated with rapidly evolving multi-organ dysfunction. The lack of liver detoxification, metabolic and regulatory functions, and an altered immune response leads to life-threatening complications, such as renal failure, increased susceptibility to infection, hepatic coma, and systemic hemodynamic dysfunction. Not surprisingly, the combined impact of these complications leads to mortality rates as high as 50 to 90%

Chronic Oral Amiodarone as a Cause of Acute Liver Failure

Acute liver failure (ALF) is defined as a loss of liver function characterized by encephalopathy, and elevation of liver enzymes and prothrombin time. It is mainly caused by acetaminophen overdose, viral hepatitis, idiosyncratic drug reactions, or hypoperfusion of the liver. Up to 30% of the patients die without liver transplantation. Drug-induced ALF can be challenging to diagnose; it should be suspected in patients with unexplained acute liver injury who are using a medication that can potentially cause hepatocellular damage. We present a case of ALF induced by chronic oral amiodarone that improved after discontinuation of the drug and supportive care.

Fulminant Hepatic Failure

Rapid onset of encephalopathy in conjunction with hepatic synthetic failure.

Hepatic Failure: An Evidence- Based Approach In The Emergency Department

The disparate causes of ALF have crucial implications for prognosis as well as intervention. In recent decades, acetaminophen toxicity and idiosyncratic drug reactions have replaced viral hepatitis as the most common causes of ALF in the US. When viral hepatitis is responsible, the overwhelming culprits are the hepatitis A and B viruses; hepatitis D rarely causes ALF in patients infected with hepatitis B, and hepatitis E is more likely in developing countries and among pregnant women. Hepatitis C rarely, if ever, causes ALF;

Management of acute liver failure

Acute liver failure (ALF) is a syndrome of diverse etiology, in which patients without previously recognized liver disease sustain a liver injury that results in rapid loss of hepatic function. Depending on the etiology and severity of the insult, some patients undergo rapid hepatic regeneration and spontaneously recover. However, nearly 60% of patients with ALF in the US require and undergo orthotopic liver transplantation or die.

Management of Acute Liver Failure in the Emergency Department

Although relatively uncommon — with only 2,000 cases annually — ALF should be included in the differential of a wide array of chief complaints because of the liver’s many functions. These can be broadly categorized as synthesis, detoxification, and storage.

Pediatric Acute Liver Failure

The Pediatric Acute Liver Failure (PALF) Study is the first multi-center, multi-national collaborative study aimed at identifying, characterizing, and developing management strategies for infants, children, and adolescents who present with acute liver failure.

Updates in the Emergency Department Management of Acute Liver Failure

we review topics related to acetaminophen hepatotoxicity, use of rifaximin and lactulose in hepatic encephalopathy, and thromboelastography (TEG) directed transfusion in patients with liver disease requiring procedures.

Resources

Anesthesia Key

The underlying cause of liver failure and the grade of the encephalopathy at time of presentation are critical determinants of outcome.

Critical Care in Emergency Medicine

Patients with acute liver failure can be incredibly sick and have an exceedingly high mortality. Early identification and prompt, evidence-based management of the patient with acute liver failure may improve patient-centered outcomes. In this podcast, we discuss updated guidelines for the management of adult patients with acute liver failure.

EMed

Very rapid progress (time jaundice to encephalopathy < 8 days) relatively better prognosis (if no cerebral oedema)

MayoClinic

Acute liver failure is less common than chronic liver failure, which develops more slowly. Acute liver failure, also known as fulminant hepatic failure, can cause serious complications, including excessive bleeding and increasing pressure in the brain. It's a medical emergency that requires hospitalization. Depending on the cause, acute liver failure can sometimes be reversed with treatment. In many situations, though, a liver transplant may be the only cure.

Mount Sinai Intensive Board Review in Gastroenterology & Hepatology

During this 20-25 minute pre-recorded lecture, Dr. James F. Crismale discusses the topic of acute liver failure. This in-depth review will provide an update on this topic for your clinical practice as well as supplement your learning for the ABIM Gastroenterology and Hepatology boards.

Patient

Fulminant hepatic failure (FHF) occurs when the failure takes place within eight weeks of the onset of the underlying illness. •Late-onset hepatic failure (also called subacute FHF) occurs when there has been a gap of 8 to 26 weeks. The difference may not immediately be obvious, as the underlying disease may have been present for a long time but undiagnosed. •Chronic decompensated hepatic failure occurs when the latent period is over six months.

UMEM Educational Pearls

Acute liver failure is defined as new and rapidly evolving hepatic dysfunction associated with neurologic dysfunction and coagulopathy (INR >1.5). Most common cause of death in these patients are multiorgan failure and sepsis. Drug-induced liver injuy most common cause in US, with viral hepatitis most common cause worldwide.