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

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.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

“…Likewise, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can cause direct virus-mediated hepatocyte injury or indirect liver immunopathology (Leonardsson et al, 2017;Dunmire et al, 2018;Kwong et al, 2019), and severe or fulminant hepatitis is recognised (Kofteridis et al, 2011;Leonardsson et al, 2017;Dunmire et al, 2018) but hepatic involvement in immunocompetent hosts is usually self-limiting. Herpes simplex virus (HSV) and varicella-zoster virus (VZV) can be complicated by dissemination with acute hepatitis and liver failure (Norvell et al, 2007;Blumental and Lepage, 2019;Little et al, 2019;Spahn et al, 2022), but the low prevalence of these viruses in AS-Hep-UA cases does not favour causality and there is a high chance that these viruses are bystanders. Enteroviruses are a recognised cause of hepatitis (ECDC, 2022e), sometimes with a severe rebound after initial improvement, in immunocompetent children and in patients receiving anti-CD20 agents and in neonates, who have an immature B-cell repertoire (Abzug, 2001;Tebruegge and Curtis, 2009;Morgan et al, 2015;Antona et al, 2016;Bajema et al, 2017;Nicolini et al, 2019).…”