Successful Treatment of Neonatal Herpes Simplex-Type 1 Infection Complicated by Hemophagocytic Lymphohistiocytosis and Acute Liver Failure

Abstract

Neonatal disseminated herpes simplex virus (HSV) infection with acute liver failure (ALF) and neonatal hemophagocytic lymphohistiocytosis (HLH) are severe diseases. We recently experienced a male infant with HLH and ALF induced by HSV type 1 (HSV-1). The infant, born at 39 weeks of gestation by normal delivery, developed a fever on day 4. On day 9, laboratory investigations showed progressive liver dysfunction and coagulopathy, and the serum ferritin was excessively elevated. Furthermore, the blood levels of interleukin (IL)-6, IL-10, and interferon-gamma were also elevated. HSV-1 DNA was detected in the serum and cerebrospinal fl uid by the real-time PCR method. A diagnosis of HLH was established based upon the following criteria: fever, splenomegaly, cytopenia (two cell lines), serum ferritin (> 500 μ g/l) and hypofi brinogenemia (< 150 mg/dl). High-dose acyclovir therapy, steroid pulse therapy using methylprednisolone, high-dose gamma globulin therapy and a blood transfusion were given. The patient recovered without neurological defi cit. Neonatal disseminated HSV infections may be complicated by the development of HLH and hypercyokinemia. If HLH is suspected, not only high-dose acyclovir therapy but also anti-cytokine therapy should be considered.newborn; herpes simplex virus type 1 infection; hemophagocytic lymphohistiocytosis; hypercytokinemia; acute liver failure.Tohoku

Changes in cellular proliferation and plasma products are associated with liver failure

“…The elevated plasma levels of IL-8 that were detected in all cases of ALF are also described in patients with drug-induced ALF and are correlated with granulocyte migration into the liver parenchyma[5,41]. The elevated levels of circulating IL-6 and TNFα, also described by others[42,43], have been related to attempts at liver regeneration[44,45] and liver injury[46], respectively. Therapeutic approaches targeting the clearance of inflammatory/toxic products (plasmapheresis, hemodiafiltration, and bioartificial livers) from the liver or anti-cytokine therapy are currently being considered[42,47-49] despite contradictory clinical results[50,51].…”

Effectiveness of Early Antiviral Therapy in Disseminated Neonatal Herpes Simplex Virus 2 (HSV-2) with Fulminant Hepatic Failure

“…Yamada et al presented a case of a 4-day-old neonate with fever and increased transaminases and lactate dehydrogenase. The patient developed disseminated HSV infection, which resulted in acute liver failure and hemophagocytic lymphohistiocytosis [17]. With the use of high-dose acyclovir and anti-cytokine therapy, this patient recovered without the need for a liver transplant and showed no neurological deficit [17].…”

“…The patient developed disseminated HSV infection, which resulted in acute liver failure and hemophagocytic lymphohistiocytosis [17]. With the use of high-dose acyclovir and anti-cytokine therapy, this patient recovered without the need for a liver transplant and showed no neurological deficit [17]. Similarly, Pilorget et al published a case report of an 8-day-old infant presenting with fever, seizures, vomiting, and liver dysfunction.…”

Persistent viral DNA detection in blood after primary herpes simplex 1 infection revealed by hepatitis with hemophagocytic syndrome

“…It commonly occurs in women during pregnancy or following a genital infection [6][7][8][9][10], and in neonatal herpes infections [11][12][13]. HSV-2 was more frequently detected in this context [6,8,10].…”