What is the recommended treatment for a patient diagnosed with Cytomegalovirus (CMV) hepatitis, especially if they are immunocompromised?

Treatment of Cytomegalovirus (CMV) Hepatitis in Immunocompromised Patients

Intravenous ganciclovir (5 mg/kg twice daily) is the first-line treatment for CMV hepatitis in immunocompromised patients, followed by oral valganciclovir (900 mg twice daily) to complete a 2-3 week course. 1, 2

Diagnosis of CMV Hepatitis

Clinical Presentation

• Fever, malaise, abdominal pain
• Elevated liver enzymes
• May present with more severe symptoms in immunocompromised patients
• Can progress to liver failure if untreated

Diagnostic Tests

• CMV PCR in blood (viral load quantification)
• CMV antigenemia assay (pp65)
• Liver biopsy with immunohistochemistry for CMV (gold standard)
  • Look for "owl eye" inclusions characteristic of CMV infection 2
• Exclude other causes of hepatitis

Treatment Algorithm

First-line Treatment

1. Initiate antiviral therapy immediately upon diagnosis

   • Intravenous ganciclovir 5 mg/kg twice daily for 3-5 days 2, 1
   • Then transition to oral valganciclovir 900 mg twice daily for remainder of 2-3 week course 2, 1

2. Consider temporary reduction of immunosuppressive therapy if possible 1

3. Monitor response to treatment

   • Serial CMV viral load measurements
   • Liver function tests
   • Clinical improvement

Alternative Treatments

• Foscarnet (90 mg/kg twice daily) for 2-3 weeks in cases of:

  • Ganciclovir resistance
  • Intolerance to ganciclovir (e.g., myelotoxicity) 2

• Cidofovir may be considered in refractory cases, though nephrotoxicity limits its use 2

Special Considerations

Severity Assessment

• More aggressive treatment is warranted for:
  • High viral loads
  • Evidence of end-organ disease
  • Significant liver dysfunction

Duration of Treatment

• Standard course: 2-3 weeks 2, 1
• May need extended treatment in severe cases or persistent viremia
• Continue treatment until:
  • Resolution of clinical symptoms
  • Normalization of liver enzymes
  • Negative viral load or significant reduction

Monitoring During Treatment

• Weekly CMV viral load monitoring 2
• Liver function tests twice weekly initially, then weekly
• Complete blood count to monitor for ganciclovir-induced neutropenia
• Renal function tests, especially if using foscarnet or cidofovir

Prevention Strategies

• No routine CMV prophylaxis is recommended for all immunocompromised patients 2
• Consider prophylaxis in high-risk patients:
  • Severe immunosuppression
  • History of prior CMV disease
  • Transplant recipients (especially D+/R-)

Important Caveats

• CMV hepatitis in immunocompromised patients has higher mortality than in immunocompetent hosts 3, 4
• Delayed diagnosis and treatment significantly worsen outcomes
• Even with appropriate treatment, mortality remains high in severe cases with multiorgan involvement
• Consider CMV hepatitis in any immunocompromised patient with unexplained liver enzyme elevation and fever

Prognosis

The prognosis for CMV hepatitis in immunocompromised patients depends on:

• Timing of diagnosis and treatment initiation
• Degree of immunosuppression
• Presence of other comorbidities
• Response to antiviral therapy

Early diagnosis and prompt initiation of appropriate antiviral therapy are crucial for improving outcomes and reducing mortality in immunocompromised patients with CMV hepatitis.