What is the management of Varicella zoster (VZV) with fulminant hepatic failure?

Management of Varicella Zoster with Fulminant Hepatic Failure

Patients with varicella zoster virus (VZV) causing fulminant hepatic failure must be immediately listed for liver transplantation and started on intravenous acyclovir without delay. 1

Immediate Actions

Transplant Listing

• List the patient immediately for emergency liver transplantation upon diagnosis or strong suspicion of VZV-induced acute liver failure (ALF). 1 This is a Level III recommendation from the AASLD, reflecting the uniformly poor prognosis without transplantation.
• VZV fulminant hepatitis is frequently fatal despite maximal medical therapy, with mortality approaching 100% without transplantation. 2, 3

Antiviral Therapy

• Initiate intravenous acyclovir immediately at 10 mg/kg every 8 hours for suspected or documented VZV hepatitis. 1, 4 Do not delay treatment while awaiting confirmatory testing.
• Treatment should continue for a minimum of 7-10 days and until clinical resolution is attained. 4
• Monitor renal function closely and adjust dosing for renal impairment, which is common in ALF. 5

Immunosuppression Management

• Reduce or temporarily discontinue immunosuppressive medications if the patient is immunocompromised (transplant recipient, on corticosteroids, chemotherapy). 1, 5
• This reduction must be balanced against the risk of organ rejection in transplant recipients, but the immediate threat to life from VZV hepatitis takes precedence. 6, 7

Diagnostic Considerations

Clinical Presentation

• Classic triad: rash, abdominal pain, and fever progressing to liver failure over days. 2
• Skin lesions are present in only approximately 50% of cases, so absence of rash does not exclude VZV hepatitis. 1
• Immunocompromised patients and pregnant women (especially third trimester) are at highest risk. 1

Diagnostic Testing

• Liver biopsy is helpful in making the diagnosis and can be confirmed by histological examination, electron microscopy with fluorescent staining, immunohistochemistry, and in situ hybridization. 1, 2
• VZV DNA by polymerase chain reaction (PCR) from blood and liver tissue confirms the diagnosis. 7, 3
• The 2017 AGA guidelines suggest against routine VZV testing in immunocompetent patients with ALF, but recommend testing in immunocompromised patients. 1

Risk Factors and Pitfalls

High-Risk Populations

• Immunosuppressed patients (transplant recipients, chemotherapy, HIV). 1, 6, 3
• Patients on corticosteroids, even short-term or low-dose therapy. 8, 3
• Pregnant women in the third trimester. 1
• Healthy individuals can rarely develop VZV hepatitis. 1

Common Pitfalls

• Delaying acyclovir while awaiting diagnostic confirmation—treatment must begin immediately on clinical suspicion. 2
• Assuming absence of rash excludes VZV—half of cases lack cutaneous manifestations. 1
• Underestimating the risk from low-dose or short-duration corticosteroids—even brief steroid exposure can precipitate fatal VZV hepatitis. 8, 3
• Failing to immediately list for transplant—medical therapy alone is insufficient, and transplantation is the only definitive treatment. 1, 6, 7

Supportive Care

General ALF Management

• Intensive care unit admission for close monitoring of hepatic encephalopathy, coagulopathy, and multiorgan failure. 1
• Monitor blood glucose at least every 2 hours to detect and treat hypoglycemia. 1
• Target serum sodium between 140-145 mmol/L to manage cerebral edema risk. 1
• Empirical broad-spectrum antibiotics if signs of sepsis or worsening encephalopathy develop. 1

Specific Monitoring

• Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose acyclovir. 5
• Monitor for severe coagulopathy, which is common in VZV fulminant hepatitis. 3
• Renal function monitoring is critical as both ALF and acyclovir can cause renal impairment. 5

Prognosis

• Mortality is extremely high (approaching 100%) without liver transplantation, even with acyclovir therapy. 6, 7, 2, 3
• Successful outcomes have been reported with emergency liver transplantation combined with perioperative acyclovir. 6, 7
• The disease typically progresses rapidly, with death occurring within 3-9 days of admission despite maximal support. 8, 3