Comprehensive clinical and virological characterization of three cases of fulminant liver failure owing to HSV1 primary infection

Liver Int. 2022 May;42(5):1005-1011. doi: 10.1111/liv.15215. Epub 2022 Mar 7.

Abstract

Herpes simplex virus 1 (HSV-1) is a frequently unrecognized, yet deadly cause of acute liver failure (ALF). We, therefore, analysed three cases of fatal HSV-1-induced ALF. All patients shared clinical (extremely elevated transaminases, LDH and AST/LDH ratio < 1) and virological characteristics (ratio of viral load in plasma versus throat swabs: 60-700-fold, lack of anti-HSV-1-IgG antibodies or low IgG-avidity during primary infection), which may help to identify patients at risk. Additionally, in vitro chemosusceptibility assays revealed high efficacy of the helicase-primase inhibitors (HPI), pritelivir and drug-candidate IM-250 compared to acyclovir (ACV) using HSV-1-isolates from two patients; hence, ACV/HPI-combinations might offer new therapeutic options for HSV-induced ALF.

Keywords: IM-250; acute liver failure; acyclovir; herpes simplex virus primary infection; pritelivir; viral hepatitis.

MeSH terms

  • Acyclovir / pharmacology
  • Acyclovir / therapeutic use
  • Antiviral Agents / adverse effects
  • DNA Helicases
  • DNA Primase
  • Herpesvirus 1, Human*
  • Humans
  • Immunoglobulin G
  • Liver Failure, Acute* / chemically induced
  • Pyridines / adverse effects

Substances

  • Antiviral Agents
  • Immunoglobulin G
  • Pyridines
  • DNA Primase
  • DNA Helicases
  • Acyclovir