Ischemic hepatitis

Ischemic hepatitis is acute, diffuse hepatocellular injury due to hepatic hypoperfusion. The most common causes are cardiopulmonary failure and sepsis. Clinical features are mostly related to the underlying cause, and symptoms related to liver injury (e.g., abdominal pain, nausea, vomiting, and anorexia) may be absent. Diagnosis is based on the clinical context and characteristic laboratory findings, such as a transient severe elevation of serum aminotransferases and increased levels of LDH and bilirubin. Management focuses on prompt identification, treatment of the underlying cause, and hemodynamic support. With appropriate intervention, hepatic injury is often reversible.

• Prevalence: Approx. 2% of individuals admitted to the ICU develop ischemic hepatitis. ^[1]
• Most common cause of severe acute liver injury in the United States ^[2]
• Approx. 80% of cases associated with underlying heart failure ^[3]

Epidemiological data refers to the US, unless otherwise specified.

• Impaired hepatic perfusion: heart failure, severe hypotension, cardiogenic shock, hypovolemic shock, thromboembolism, cardiac tamponade
• Hypoxemia: respiratory failure
• Increased metabolic demand: septic shock, extensive burns, surgery

Referring to ischemic hepatitis as “shock liver” is not recommended, as hypoxic liver injury can occur without shock. ^[4]

Pathophysiology of hepatic tissue hypoxia and necrosis:

• Hepatic congestion due to an underlying condition (e.g., heart failure) → hepatic structural changes (e.g., sinusoidal centrilobular dilation, hepatocyte atrophy) and ↓ hepatic blood flow
• Low cardiac output, hypovolemic shock, or cardiac arrest → ↓ hepatic blood flow
• Septic shock: ↑ hepatic metabolic needs → ↓ O₂ extraction capacity, circulating endotoxins, and inflammatory cytokines → ↓ ability of hepatocytes to extract and use oxygen→ ↓ hepatic blood flow

• Symptoms related to liver injury may be absent.
• Fatigue, weakness, altered mental status (AMS)
• Hypotension, tachycardia
• Nausea, vomiting, anorexia, right upper quadrant tenderness, hepatomegaly
• Clinical features of associated complications (e.g., hepatopulmonary syndrome, hyperglycemia, hypoglycemia, and/or hyperammonemia)

General principles ^[5]

• Suspect ischemic hepatitis in patients with both:
  • Hemodynamic instability and/or respiratory failure
  • Transient severe transaminitis and elevated LDH levels
• Exclude alternative causes of elevated transaminases (e.g., acetaminophen toxicity, acute viral hepatitis).
• Imaging and biopsy are not required for diagnosis.

Laboratory studies ^[5]

• Liver function tests
  • Severe transaminitis ^[4]
    • Typically AST > ALT; levels often > 1000 U/L ^[6]
    • Serum levels peak 1–3 days after ischemic injury and typically normalize within 7–14 days. ^[6]
  • ↑ Bilirubin
  • ↑ LDH
  • ALT:LDH ratio < 1.5 ^[7]
  • Normal alkaline phosphatase
• Renal function tests: Serum creatinine and BUN may be elevated. ^[8]
• Coagulation studies: INR and prothrombin time may be prolonged.
• Tests to exclude other causes of acute liver injury, e.g.:
  • Acetaminophen levels (see “Acetaminophen overdose.”)
  • Acute viral hepatitis panel

AST > 400 U/L should raise concern for ischemic hepatitis or drug-induced liver injury. ^[9]

Imaging studies ^[5]

• Abdominal ultrasound with Doppler: to evaluate vasculature (e.g., dilated hepatic veins, abnormal flow in hepatic artery or portal vein)
• Echocardiogram: may show evidence of cardiac dysfunction

• Diffuse hepatic injury
• Centrilobular necrosis (zone 3 of the hepatic acinus) with very few inflammatory cells

• Drug-induced liver injury (due to, e.g., acetaminophen; or herbal supplement poisoning)
• Acute viral hepatitis
• Hepatic infarction
• See “Common causes of severe elevation of transaminases.”

The differential diagnoses listed here are not exhaustive.

There is no specific treatment for ischemic hepatitis. ^[5]

• Provide management of acute liver failure if present.
• Treat the underlying cause.
• Provide hemodynamic support and optimize cardiac output (e.g., with diuretics in hypervolemia).
• Consult hepatology for patients who do not improve with supportive management.
• Monitor for evidence of end-organ hypoperfusion with, e.g.:
  • Serial BMPs for renal failure
  • Confusion assessment method for AMS

• Depends on the underlying condition, duration, and extent of the hemodynamic compromise
• Factors associated with higher mortality rates include: ^[10][11]
  • Necessity of vasopressor therapy
  • Prolonged INR
  • Septic shock
  • Renal failure