Hepatic Failure/GI/Endocrine Emergencies

Incidence of ALF is less than 10 cases per 1 million individuals per year (2000 cases per year in the

United States), though morbidity and mortality are exceedingly high with ALF. Multiorgan failure and

death occur in as many as 50% of patients.

ALF can occur in any age and demographic group, though the etiology of ALF is sometimes

geographically dependent. Viral hepatitis cases are more common in developing countries, whereas

toxin-related cases (e.g., those related to acetaminophen) occur more often in developed countries.

The most common causes in the United States are drug induced, viral, autoimmune, and shock. Drug-

induced causes, primarily acetaminophen, account for about 50% of the ALF cases in the United States.

About 15% have no identifiable cause.

The mortality rate has decreased significantly during the past few decades because of advances in

medical care and early consideration for liver transplantation. Survival rates for ALF now exceed 65%,

whereas before early transplantation, survival rates were less than 15%.

ALF is defined by the U.S. Acute Liver Failure Study Group (ALFSG) and the American Association

for the Study of Liver Diseases (AASLD) as evidence of liver-induced coagulopathy, defined as an INR

of 1.5 or greater, and any degree of mental alteration (encephalopathy) in a patient without preexisting

liver failure and with an illness duration less than 26 weeks.

ALF is in contrast to ACLF (acute-on-chronic liver failure), which is a syndrome defined on the

basis of acute decompensation of chronic liver disease and presence of multiorgan failure.

These intervals typically provide clues regarding the cause of the ALF; however, the differentiation

itself generally has no prognostic implications distinct from the causes themselves.

Hyperacute ALF: Encephalopathy occurs less than 7 days after the onset of jaundice. This subclass

of ALF is typically caused by acetaminophen toxicity or ischemic hepatitis and is associated

with higher rates of transplant-free survival defined as survival free of liver-related death or liver

transplantation. Patients tend to have high-degree encephalopathy at presentation and a higher

incidence of cerebral edema, albeit a better prognosis overall.

Acute ALF: Encephalopathy occurs 7–21 days after the onset of jaundice. Common causes of acute

ALF include viral hepatitis. These patients have a high incidence of cerebral edema, but unlike in

hyperacute ALF, lower rates of transplant-free survival.

Subacute ALF: Encephalopathy occurs more than 21 days and less than 26 weeks after the onset of

jaundice. Typical causes are drug induced or indeterminate. This subclass is associated with lower

transplant-free survival, though patients have less marked coagulopathy and encephalopathy at

presentation and may more often develop renal failure and portal hypertension.

An unexplained elevated INR in a patient presenting with encephalopathy requires further evaluation

for ALF because the combination of these two symptoms is very specific to ALF.

portal hypertension) may not be present.

Additional physical examination, laboratory analysis, and imaging necessary for the diagnosis and

workup of ALF are shown in Table 1.