Gastrointestinal System

Diagnosis and reasoning

The patient with altered mentation is a common presentation in the emergency department, with differentials ranging from traumatic brain injury to stroke, central nervous system (CNS) infections, metabolic derangements, and drug overdose or intoxication.

However, this specific patient has several important clues which vastly narrow down the list of possibilities: jaundice, an inverted sleep pattern, asterixis, and moderate hepatomegaly.

The above constellation of symptoms is strongly suggestive of acute liver failure (ALF) complicated by grade II hepatic encephalopathy (HE). This is supported by the liver profile, which shows massive elevations of transaminase levels, a marked coagulopathy, and direct hyperbilirubinemia.

ALF and HE are both medical emergencies with a high mortality. The patient should be immediately transferred to an intensive care unit (ICU), stabilized, and closely monitored. It is only afterward that a search should be made for the underlying etiology.


ion of ALT and AST to the currently seen levels occur in only a few conditions. These include acute viral hepatitis, acetaminophen poisoning, toxic injury (for example, due to amatoxins found in mushrooms), and ischemic hepatitis.

Note that despite the history of heavy alcohol consumption, alcoholic hepatitis is unlikely. In this condition, transaminase levels are much lower (in the hundreds), and AST levels are higher than ALT levels, with an AST:ALT ratio of ≥2.0.

The negative acute hepatitis panel makes acute viral hepatitis unlikely as well, although the possibility that he is within the lag period should be kept in mind. Neither is there a history of ingestion of mushrooms or other potential toxins.

Acetaminophen levels are not elevated either, although, given the time interval since the onset of symptoms, this does not exclude poisoning.

Ischemic hepatitis is mainly a diagnosis of exclusion. That said, there is no evidence of current or previous shock or cardiovascular instability which would precipitate this.

Thus, there is no obvious cause of the ALF. In the absence of other evidence, this should probably be considered to be due to poisoning or toxicity until proven otherwise.

N-acetylcysteine therapy is essential. This has been shown to result in increased rates of survival in both acetaminophen and non-acetaminophen related ALF.

Administration of lactulose will ameliorate the HE, by both inhibiting intestinal ammonia production and reducing the colonic bacterial load (as it is an osmotic laxative).

Note that sedation with benzodiazepines is contraindicated in HE, as this may further impair mentation.


Acute liver failure (ALF) is a medical emergency characterized by sudden massive hepatic necrosis giving rise to jaundice, coagulopathy, and ultimately, hepatic encephalopathy.

While uncommon in the western world, with an estimated incidence of less than 1 in 100,000 persons per year, it is much more common in developing countries.

ALF can occur at any age and affects both genders. The causative etiologies are diverse, including toxic, infective, metabolic and vascular causes.

However, poisoning and toxins are the key causes in the developed world, while acute viral hepatitis is the most prominent cause in developing countries. Other causes include Wilson disease, HELLP syndrome, Budd-Chiari syndrome, heat shock, malignant infiltration, and autoimmune hepatitis.

Note also that ALF can be classified as either hyperacute, acute or subacute, based on the time interval between the initial onset of jaundice, and subsequence development of encephalopathy.

The initial clinical features are often nonspecific, e.g. anorexia, fatigue, abdominal pain, and fever. As the disease progresses, the presentation varies greatly, ranging from marginally altered mental status to subtle degrees of coagulopathy, to a fatal state of multiple organ failure.

As liver functions begin to deteriorate, more prominent signs emerge, including jaundice, overt coagulopathy (i.e. an INR > 1.5), encephalopathy, hemodynamic instability, acute respiratory distress syndrome, renal failure, metabolic disturbances, and sepsis.

Note that encephalopathy can progress rapidly, from subtle alterations of mental status (e.g. minor confusion, disorientation, and agitation), to a severe syndrome with delirium, seizures, and coma. Cerebral edema may also occur.

History taking should include a careful assessment of possible exposure to viral infection, drugs, and other toxins. The examination should include a close evaluation of mental status, and search for the stigmata of cirrhosis.

Key investigations include estimation of either prothrombin time or INR. If the former is found to be prolonged by >4 to 6 seconds, or the latter is >1.5, and the patient's sensorium is altered, the diagnosis of ALF can be established.

Where ALF is diagnosed, admission to an intensive care unit should be strongly considered, as the patient's condition may decline rapidly.

N-acetylcysteine (NAC) should be administered without delay, as it has been associated with increased rates of survival in both acetaminophen and non-acetaminophen related ALF.

Antibiotics should be considered in persons with coagulopathy, organ failure, encephalopathy, or if disease progression is considered likely.

Administration of coagulation factors should be avoided, except where there is dire need of bleeding control, or prior to invasive procedures. This is because the serial evaluation of coagulation variables is essential to monitoring recovery, and determining the prognosis.

Further management is aimed at detecting and treating the underlying etiology and prevention of damage to other organs. Note that in persons with irreversible liver injury, orthotopic liver transplantation (OLT) remains the only means of treatment.

While the presence of encephalopathy is crucial in determining the prognosis of ALF, other factors including the patient's age and the degree of liver insult also need to be taken into consideration.

In particular, the onset of encephalopathy holds prognostic significance. In hyperacute ALF, poor prognosis is indicated only by high-grade encephalopathy, but in subacute ALF, even low-grade encephalopathy reflects a poor prognosis.

Take home messages

1. Acute liver failure (ALF) is a life-threatening illness that presents with jaundice, hepatic encephalopathy, and coagulopathy.

2. In the developed world, toxic insults are the most common cause of ALF. In developing countries, it is viral hepatitis which is the key cause.

3. The presence of encephalopathy and coagulopathy indicate that severe ALF is present.

4. N-acetylcysteine (NAC) therapy improves outcomes and is indicated in all patients, regardless of etiology.


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