What is the appropriate management of acute hepatitis occurring in a patient with varicella‑zoster infection?

Management of Acute Hepatitis in Varicella-Zoster Infection

Patients with acute hepatitis from varicella-zoster virus (VZV) require immediate hospitalization, high-dose intravenous acyclovir, reduction or temporary cessation of immunosuppression (if applicable), and urgent evaluation for potential liver transplantation given the high mortality risk of VZV-associated fulminant hepatic failure. 1, 2, 3

Immediate Risk Stratification and Hospitalization Decision

All patients with VZV-associated acute hepatitis warrant hospital admission given the risk of rapid progression to fulminant hepatic failure, which occurs frequently and is often fatal in this population. 3, 4, 5

Key indicators requiring immediate hospitalization include:

• INR ≥1.5 with any degree of mental status change or encephalopathy 2, 6
• Severe nausea/vomiting preventing adequate oral intake 2, 6
• Bilirubin >10× upper limit of normal with significant jaundice 2, 6
• Any signs of hepatic encephalopathy or altered mental status 2, 6
• Presence of disseminated VZV infection (rash, pneumonia, or other organ involvement) 3, 7

Antiviral Therapy

Initiate high-dose intravenous acyclovir immediately upon suspicion of VZV hepatitis, without waiting for confirmatory testing. 1, 5

• For systemic/disseminated VZV infection with hepatitis: intravenous acyclovir is mandatory 1
• Continue IV acyclovir until clinical response is achieved, then consider switching to oral therapy (valacyclovir or acyclovir) to complete 14-21 days total treatment 1
• Do not delay acyclovir therapy in cases of high clinical suspicion, as progression to fulminant hepatic failure can occur within days 4, 5

Important caveat: Case reports demonstrate that acyclovir may be ineffective in preventing progression to fulminant hepatic failure in some patients, particularly those with extremely virulent VZV strains or co-infections. 3, 4

Immunosuppression Management

Reduce or temporarily cease immunosuppressive medications immediately in transplant recipients or other immunosuppressed patients with VZV hepatitis. 1, 7

• This applies to all patients on immunosuppression, including those on even low-dose, short-term corticosteroids 4
• Balance the risk of organ rejection against the life-threatening nature of disseminated VZV infection 7

Critical Monitoring Parameters

Monitor the following parameters closely to detect progression to acute liver failure:

• INR, bilirubin, ALT, AST every 2-4 weeks initially, but more frequently (daily or twice daily) if hospitalized 2, 6
• Mental status assessment frequently for subtle signs of encephalopathy 2, 6
• Blood glucose at least every 2 hours, as hypoglycemia is common in acute liver failure 2, 6
• Renal function and electrolytes 2
• Signs of disseminated intravascular coagulation, pneumonia, or other organ involvement 7

Early Transplant Evaluation

Contact a liver transplant center immediately when any of the following develop:

• INR >1.5 with any degree of encephalopathy 2, 6
• Progressive bilirubin elevation despite supportive care 2
• Development of multi-organ failure 2, 6
• Meeting King's College criteria for transplantation 2

Total hepatectomy as a bridge to urgent liver transplantation may be considered in cases of fulminant hepatic failure with severe hemodynamic instability, though outcomes remain poor. 3, 8

Supportive Care Measures

Avoid all hepatotoxic medications, particularly acetaminophen, and ensure complete alcohol abstinence. 1, 6

For patients requiring IV fluids:

• Use balanced crystalloid solutions (Ringer's lactate, Plasmalyte, or Isofundine) over normal saline 9
• In severe acute hepatitis or evolving acute liver failure, avoid lactate-containing solutions and use acetate-buffered solutions (Plasmalyte or Isofundine) instead 9
• Monitor carefully for fluid overload, as patients may develop ascites or altered oncotic pressure 9

Additional Considerations

Consider varicella-zoster immunoglobulin (VZIG) or intravenous immunoglobulin (IVIG) in addition to acyclovir, particularly in severely ill patients, though evidence is limited. 8, 7

Maintain high clinical suspicion for VZV hepatitis when:

• Atypical or concurrent skin lesions are present with acute hepatitis 3, 5
• Patient has recent exposure to varicella or herpes zoster 4
• Patient is in a temporarily immunocompromised state (including recent low-dose steroid use) 3, 4
• Classic presentation includes rash, abdominal pain, and fever progressing to liver failure over days 5

Critical pitfall: VZV hepatitis can occur in immunocompetent adults, possibly due to extremely virulent strains, and should not be dismissed based on immune status alone. 3, 4 Co-infection with other herpesviruses (such as HHV-6) may worsen outcomes. 3