In-Hospital Outcomes of Acyclovir With or Without Corticosteroid for Herpes Simplex Encephalitis: A Nationwide Retrospective Cohort Study.

BACKGROUND AND

OBJECTIVES

Acyclovir is the standard therapy for herpes simplex virus (HSV) encephalitis, yet mortality remains high. Secondary inflammatory responses triggered by viral infection potentially contribute to additional brain injury. Given their anti-inflammatory properties, corticosteroids are considered a biologically plausible adjunctive treatment for HSV encephalitis. However, evidence regarding their effects remains inconclusive, highlighting the need for large-scale evidence.

METHODS

We conducted a retrospective cohort study using the Japanese national inpatient Diagnosis Procedure Combination database. We included patients hospitalized with HSV encephalitis who received intravenous acyclovir within 2 days of admission. Patients were divided into the acyclovir plus corticosteroid group or the acyclovir-alone group based on whether they received intravenous corticosteroids at a prednisolone-equivalent dose of ≥30 mg/d within 2 days of admission. The primary outcome was in-hospital mortality. Secondary outcomes included discharge alive with full consciousness, discharge alive with functional independence, length of hospital stay, and hospitalization costs. Outcomes were compared using multivariable regression models adjusted for baseline confounders.

RESULTS

A total of 3,933 patients (mean age, 58.9 years; 58.1% male) were included: 1,385 patients in the acyclovir plus corticosteroid group and 2,548 in the acyclovir-alone group. The adjusted outcomes in the acyclovir plus corticosteroid and acyclovir-alone groups were, respectively, in-hospital mortality, 4.2% and 3.2% (difference, 1.0%; 95% CI -0.6% to 2.1%); discharge with full consciousness, 75.3% and 75.0% (difference, 0.3%; 95% CI -2.6% to 2.6%); and discharge with functional independence, 62.7% and 61.9% (difference, 0.8%; 95% CI -1.8% to 3.7%). The adjusted length of hospital stay was longer (35.5 and 29.6 days; difference, 5.9 days; 95% CI 3.8-8.0 days), and hospitalization costs were higher ($14,704 and $12,174; difference, $2,530; 95% CI $1,774-$3,277) in the acyclovir plus corticosteroid group.

DISCUSSION: Early adjunctive corticosteroid therapy was not associated with lower in-hospital mortality or better functional outcomes in patients with HSV encephalitis. Although our findings do not support the routine use of early adjunctive corticosteroids, further studies evaluating the optimal indications, timing, and duration of corticosteroid administration are needed to clarify its potential role in the management of HSV encephalitis.