Time to Consider Empiric Acyclovir

Abstract

Purpose: A 63-year-old female presented to the emergency department with a two-day history of fever of 101.9°F and worsening fatigue. She denied a history of liver disease and was otherwise in good health, aside from a history of arthritis. She denied any recent changes in medications, use of antibiotics or travel history. Urine toxicology screen, acetaminophen level and hepatitis A-C serology were negative. Her laboratory assessment was notable for AST 4755 IU/L, ALT 3569 IU/L and an INR of 1.4. She was admitted into her local hospital and started on intravenous N-acetylcysteine. Overnight, she developed subtle changes in behavior without any change in level of consciousness. She was subsequently transferred to a liver transplant center. Upon arrival, the patient was oriented, but very somnolent, and remained febrile at 103.1°F. Physical exam was negative for stigmata of chronic liver disease, rash or asterixis. Laboratory assessment revealed total bilirubin 0.6 mg/dl, AST 7392 IU/L, ALT 5942 IU/L, INR of 2.2, WBC 2900 cells/ mm3, hemoglobin 16 g/dL and platelets of 29,000/mm3. Abdominal ultrasound showed a normalappearing liver with normal hepatic and portal flow. Further history from family revealed the patient was taking oral prednisone the past few weeks for chronic joint pain. Given this history, combined with fever, leukopenia and anicteric hepatitis, she was started on empiric IV acyclovir for possible herpes simplex virus (HSV)-induced liver failure. She underwent expedited liver transplant evaluation. A trans-jugular liver biopsy revealed minimal inflammation with scattered hepatocyptes with glassy nuclear inclusions, azonal areas of necrosis and positive HSV stain. Her serum HSV DNA testing by PCR was 1.2 x 10ˆ6 copies/ml, although her initial HSV IgM was within reference range. Her laboratory values normalized completely within 15 days, and she was discharged to a local rehab center. HSV-induced liver failure accounts for only 1% of all ALF, but confers a mortality rate of 75%. Although immunocompetent patients can be affected, 75% of affected patients are immunosuppressed or pregnant in the third trimester. Patients who present with fever, vesicular skin lesions, leukopenia and anicteric hepatitis need to be considered for empiric acyclovir therapy and transferred to a liver transplant center. Serological testing with antibodies against HSV in the serum is nonspecific and has low utility in early treatment decisions. Confirmation of diagnosis is best performed with liver biopsy and serum HSV PCR. Empiric therapy with acyclovir for patients at risk may obviate the need for liver transplantation.