Prolonged acyclovir therapy for Herpes simplex virus (HSV)-1–associated hepatitis in an immunocompetent man

Herpes simplex virus (HSV)-associated hepatitis (HH) has rarely been reported in immunocompetent patients. In the absence of mucocutaneous lesions and because of nonspecific biological features such as hepatic cytolysis, its diagnosis can be missed, leading to delayed acyclovir initiation and potentially poor outcomes. We report a case of a 62-year-old immunocompetent man who developed severe HH following a primary HSV-1 infection, diagnosed by a very high plasma HSV-1 DNA load. His condition was complicated by macrophage activation syndrome, which was managed using chemotherapy and corticosteroids. Acyclovir therapy (10 mg/kg every 8 ,h) was extended to Day 74 to a persistently detectable plasma HSV-1 DNA load, despite the normalisation of liver function tests. However, the optimal duration of antiviral therapy for HH remains unclear, as prolonged treatment may increase the risk of nephrotoxicity, whereas premature discontinuation may lead to fatal outcomes. Overall, this case illustrates that discontinuation of acyclovir did not result in a rebound of HSV-1 viraemia despite the persistent detection of low viral DNA load. Clinical and biological resolution of hepatitis may be helpful in guiding the decision to discontinue antiviral therapy. This case highlights the importance of early molecular diagnosis in atypical presentations of HH and contributes to guiding management strategies, particularly regarding antiviral treatment duration.