Liver Failure, Acute

Key Features

Essentials of Diagnosis

• May be fulminant or subfulminant and both carry an equally poor prognosis

• Acetaminophen and idiosyncratic drug reactions are the most common causes

General Considerations

• Acute liver failure may occur after reactivation of hepatitis B in carriers who receive immunosuppressive therapy

• In fulminant liver failure, encephalopathy and coagulopathy develop within 8 weeks after the onset of acute liver injury

• Subfulminant liver failure occurs when encephalopathy and coagulopathy appear between 8 weeks and 6 months after the onset of acute liver injury

• Acute-on-chronic liver failure

  • Refers to acute deterioration in liver function in a person with preexisting chronic liver disease

  • Often precipitated by infection or an alcohol binge and alcoholic hepatitis

• Toxicity caused by acetaminophen accounts for 45% of cases; idiosyncratic drug reactions are the second most common

• Among cases caused by acetaminophen

  • 44% are due to suicide attempts

  • 48% are due to unintentional overdose (the threshold for liver failure is lowered by chronic alcohol use)

ETIOLOGY

• Acetaminophen toxicity

• Idiosyncratic drug reactions

• Mushroom poisoning (Amatoxins)

• Viruses (hepatitis A, B, C, D, E, CMV, EBV, HSV, parvovirus B19, influenza virus, yellow fever virus, Middle East respiratory syndrome virus, Ebola virus, SARS coronavirus)

• Shock

• Hyperthermia

• Budd-Chiari syndrome

• Malignancy (especially lymphomas)

• Wilson disease

• Reye syndrome

• Fatty liver of pregnancy and other disorders of fatty acid oxidation

• Autoimmune hepatitis

• Grand mal seizures (rarely)

• Cause is indeterminate in approximately 5.5% of cases

Demographics

• Most cases in the United States are caused by

  • Acetaminophen toxicity

  • Idiosyncratic drug reactions

  • Acute viral hepatitis, especially hepatitis B

  • Some cases are due to hepatitis A or unknown (non-ABCDE) viruses

• In endemic areas, hepatitis E is an important cause of acute liver failure particularly in pregnant women

• Hepatitis C is a rare cause of acute liver failure; acute hepatitis A or B superimposed on chronic hepatitis C has a high risk of acute liver failure

Clinical Findings

Symptoms and Signs

• Gastrointestinal symptoms (nausea, vomiting, anorexia)

• Jaundice may be absent or minimal early

• Systemic inflammatory response

• Acute kidney injury

• Clinically significant bleeding is uncommon and reflects severe systemic inflammation rather than coagulopathy

Diagnosis

Laboratory Tests

• Severe hepatocellular damage (Table 16–3)

• Coagulopathy

• Elevated serum ammonia; correlates with development of encephalopathy and intracranial hypertension

• In acetaminophen toxicity, serum aminotransferase elevations are often towering (> 5000 units/L), and acetaminophen is undetectable in plasma in 50% of cases

• Acetaminophen-protein adducts in serum and other biomarkers for early detection are under study

• In acute liver failure due to microvesicular steatosis (eg, fatty liver disease of pregnancy), serum aminotransferase elevations may be modest (< 300 units/L)