Epidemiology and Prognostic Factors of Herpes Simplex Virus Encephalitis in Japan: A Nationwide Database Study

Herpes simplex virus encephalitis (HSE) is a rare but life-threatening condition. While the disease has been well characterized in Western countries, large-scale epidemiological data from Japan are lacking.

Using the Ministry of Health, Labour and Welfare (MHLW) Diagnosis Procedure Combination (DPC) Study Group database, we identified patients hospitalized with HSE between July 2010 and March 2023. Patients were identified using International Classification of Diseases, 10^th Revision codes. Nationwide incidence was estimated by multiplying the observed case counts by the annual ratio of total discharges in the national MHLW-DPC database to those in the DPC Study Group. We used generalized estimating equations to account for clustering within hospitals in multivariable models. In-hospital mortality and functional and neurological outcomes were assessed. Multivariable logistic regression identified prognostic factors.

A total of 6,788 patients were identified. The annual incidence of HSE ranged from 5.7 to 8.2 per 100,000 hospitalizations. Overall, in-hospital mortality was 6.0%. Of 6,378 survivors, 2,295 (36.0%) had a Barthel Index score ≤90 and 1,602 (25.1%) had impaired consciousness (Japan Coma Scale ≥1) at discharge. A composite poor outcome (death or impaired consciousness) occurred in 2,012 (29.6%). Older age (especially ≥80 years), impaired consciousness at presentation, and comorbidities such as congestive heart failure, chronic renal disease, malignancy, and underweight status were associated with in-hospital mortality and poor outcomes.

This multicenter analysis of HSE in Japan showed that HSE was associated with substantial disability among survivors, in addition to non-negligible mortality. Our findings highlight the need for post-acute rehabilitation to reduce the burden of residual disability.