Evaluation and Management of Liver Failure
Kevin M. Korenblat
I. GENERAL PRINCIPLES
A. Acute liver failure (ALF), also known as fulminant hepatic failure, is a rare condition defined as the development of coagulation disturbance and encephalopathy in individuals without cirrhosis and with an illness of <26 weeks duration.
1. Wilson disease and autoimmune hepatitis can be included in this diagnosis when the initial presentation is as an acute illness even if cirrhosis is present.
B. Chronic liver failure results from continuous hepatic injury over a prolonged time period and typically is characterized by the following:
1. Cirrhosis of the liver.
2. Portal hypertension.
II. ACUTE LIVER FAILURE
A. Etiology.
1. The causes of ALF are many (Table 78-1). Identification of the cause of ALF is important for several reasons:
a. Specific treatments are available.
b. Infectious causes may have implications for public health and be amenable to postexposure prophylaxis.
c. Prognosis varies with cause.
2. Acetaminophen overdose is the most common cause of ALF in the United States.
a. Acetaminophen hepatotoxicity can be the consequence of both intentional and unintentional overdosage.
i. Hepatotoxicity typically occurs when dosages exceed a threshold of 150 mg/kg body weight.
ii. Individuals at risk for depletion of intracellular glutathione (e.g., chronic alcohol use) or those with increased cytochrome P-450 2E1 activity (e.g., chronic anticonvulsive exposure) can experience severe hepatotoxicity with doses as low as 3 to 4 g/day.
b. One-third of overdoses may be unintentional; these unintentional overdosages have been associated with greater morbidity and mortality than intentional overdosages.
TABLE 78-1 Causes of Acute Liver Failure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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3. ALF from viral hepatitis can result from infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis E virus (HEV), and herpes simplex virus (HSV); ALF from hepatitis C is extremely rare.
a. HAV infection is treated with supportive care.
b. ALF can occur with acute HBV infection or reactivation of inactive infection. The risk of reactivation should be considered in the immunosuppressed subject.
c. HSV hepatitis can occur in a variety of subjects: healthy individuals, the immunosuppressed and pregnant women in the third trimester.
i. HSV hepatitis is typically characterized by very high aminotransferases, though jaundice is unusual (anicteric hepatitis). Prompt treatment of known or suspected cases of HSV hepatitis with acyclovir (5 to 10 mg/kg IV every 8 hours) may be lifesaving.
4. Drug-induced liver injury (DILI) accounts for an estimated 13% of ALF in the United States.
B. Complications.
1. Encephalopathy and cerebral edema.
a. By definition, all patients with ALF have encephalopathy, with symptoms ranging from subclinical confusion (grade 1) to coma (grade 4).
b. Cerebral edema occurs in up to 80% of patients with ALF and grade 4 encephalopathy and can result in death from brain herniation.
2. Coagulopathy.
a. Prolongation of the international normalized ratio (INR) and activated partial thromboplastin time occurs as a consequence of reduced hepatic synthesis of vitamin K-dependent coagulation factors.
3. Cardiorespiratory complications.
a. Typical hemodynamic changes in ALF mimic distributive shock: increased cardiac output, decreased peripheral oxygen extraction, and low systemic vascular resistance.
b. The development of arterial hypertension may herald the development of cerebral edema.
4. Renal failure.
a. Renal failure in ALF can result from acute tubular necrosis, prerenal azotemia, or the hepatorenal syndrome (HRS).
b. In acetaminophen overdosage, acute tubular necrosis from the effect of the toxic metabolite on the kidney can be observed in as many as 75% of cases.
5. Metabolic disorders.
a. Lactic acidosis develops as the combined consequence of tissue hypoxia with increased lactate production and impaired hepatic metabolism of lactate. Renal dysfunction also may contribute.
b. Hypoglycemia occurs as a consequence of the loss of hepatic gluconeogenesis and glycogenolysis and signifies severe hepatocellular injury.
6. Infection.
a. The most common organisms isolated include Staphylococcus, Streptococcus, gram-negative enteric organisms, and Candida spp.
b. Fungal infections occur late in the course of illness and are associated with high mortality.
c. Signs of infection can be protean; one-third of septic subjects may be a febrile and lack leukocytosis.
C. Treatment.
1. General measures.
a. Early identification of the cause of ALF is critical.
