Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient

Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.     

A fatal case of Herpes simplex virus meningoencephalitis in an immunocompetent adult

Management of herpes simplex virus encephalitis (HSE) has been considerably improved by the development of rapid polymerase chain reaction (PCR) assays and by the use of intravenous acyclovir. However, an absence of early antiviral treatment has been associated to a poor outcome in patients with HSE. In the present report, we described the case of a 53 years-old adult immunompetent patient who was admitted to the emergency department of university medical center of Reims (France). At the time of hospitalisation, he was suffering from a febrile encephalitis syndrome evolving for more than 24 hours. A cerebrospinal fluid (CSF) puncture was performed demonstrating the presence of a lymphocytic meningitidis (42 leukocytes/mm3 which 90% of mononuclear cells; CSF protein = 1650 mg/L) associated with high levels of interferon alpha (75 UI/mL). Specific herpesvirus PCR and hybridisation assays (Herpes Consensus Hybridowell, Argene, France) were positive for the detection of HSV-1 genome on this CSF sample. Despite the intravenous acyclovir treatment (15 mg/kg/8 hours) delivered at the time of hospitalisation, this immunocompetent adult patient will dead 15 days later by a cardiorespiratory failure that was related to extensive HSE lesions. The time delay between the beginning of the clinical syndrome and the instauration of intravenous acyclovir treatment (more than 24 hours) was the only point susceptible to explain the presence of extensive CNS lesions in this patient. Specific Herpesvirus PCR detection assays are powerful tools that are actually used to establish a rapid etiological diagnosis of viral meningo-encephalitis. However, in patients demonstrating clinical signs of encephalitis associated with an aseptic CSF, it remains essential to urgently initiate a presumptive intravenous acyclovir treatment (10-15 mg/kg/8 hours). Actually, this medical practice is the only one susceptible to reduce the morbi-mortality rates linked to HSE.     

Herpes simplex virus infections

Infections with herpes simplex virus (HSV) are extremely common. HSV infection may be asymptomatic or may cause any one of a wide variety of disease syndromes. In this review, the physical properties and mode of replication of HSV are briefly described, and an outline of the different clinical manifestations associated with HSV infection is presented. Principles of diagnosis, treatment, and prevention of these infections are also discussed.     

Disseminated herpes simplex virus infection with hepatitis in an adult renal transplant recipient

A rare occurrence of disseminated herpes simplex virus infection with hepatitis in an adult renal transplant recipient is described.     

Herpes simplex hepatitis in apparently immunocompetent adults

A study of eight cases of herpes simplex hepatitis in apparently immunocompetent adults is presented. The clinical features were nonspecific and were usually those of a severe systemic infection, mimicking septic shock. However, the histologic features were distinctive, with randomly distributed patchy areas of coagulative necrosis surrounded by hepatocytes containing viral inclusions. Viral particles could be identified by electron microscopy and Herpes simplex antigens by immunohistochemistry, but these were not necessary for diagnosis. The light microscopic morphologic features are so distinctive that if these are recognized in a biopsy, the diagnosis of herpetic hepatitis can be made and anti-viral therapy may be instituted.     

Herpes simplex virus resistance to antiviral drugs.

Herpes simplex virus (HSV) infections are efficiently treated with antiviral drugs such as acyclovir (ACV). However, resistance has been reported, mainly among immunocompromised patients (prevalence around 5%) and particularly allogeneic bone marrow transplant patients (prevalence reaching 30%). Resistance to ACV is associated with mutations on one of the two viral enzymes involved in the ACV mechanism of action: thymidine kinase (TK) and DNA polymerase. In 95% of the cases, ACV resistance is associated with a mutation in the TK gene as this enzyme is not essential for viral replication, unlike viral DNA polymerase, which is rarely involved in resistance. Strains resistant to ACV are almost always cross-resistant to other TK-dependent drugs such as penciclovir and famciclovir. Resistant infections can be managed by foscarnet or cidofovir but both are more toxic than ACV. These drugs also inhibit viral DNA polymerase but they are active on most ACV-resistant HSV as they do not depend on TK; nevertheless virus resistant to ACV because of a mutation in the DNA polymerase may be cross-resistant to these molecules. Published data on genetic characterization of resistant clinical isolates point out hot spots in viral TK and DNA polymerase genes. TK mutations associated with resistance are either insertion or deletion (codons 92 and 146 of TK gene) or substitution (codon 176-177, 336 of TK gene). DNA polymerase mutations are mainly located in conserved sites of the enzyme. A high level of gene polymorphism has also been reported for these genes, especially for TK. These results are useful for the development of rapid genotypic assays for the detection of mutations associated with resistance.     

Herpes simplex virus hepatitis in mice: effects of treatment with trisodium phosphonoformate

Clinical isolates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) induced focal necrotic hepatitis in ICR/Sch? mice. The extent of the hepatitis could be considerably reduced by trisodium phosphonoformate (PFA) administered for 3 days in a daily dose of 400-600 mg/kg. The HSV hepatitis in mice could serve as a suitable model for testing antiherpetic drugs.     

Chronic meningitis due to herpes simplex virus in an immunocompetent host

Herpes simplex virus (HSV) typically causes mucocutaneous disease, encephalitis, and acute meningitis. There have been no previous reports of chronic meningitis due to this virus. A case of chronic meningitis due to herpes simplex virus type 2 (HSV-2) in a previously healthy 35-year-old woman whose predominant symptoms were headache and meningism without fever is described. Analysis of cerebrospinal fluid (CSF) revealed a lymphocytic pleocytosis, elevated protein, and hypoglycorrhachia. The diagnosis of herpes simplex meningitis was supported by the detection of HSV-2 DMA in CSF by polymerase chain reaction and by intrathecal production of HSV-specific antibody. The patient recovered after treatment with intravenous acyclovir and glucocorticoids.     

Immunity in latent Herpes simplex virus infection

Immune responses against productive Herpes simplex virus 1 (HSV-1) and/or Herpes simplex virus 2 (HSV-2) (HSV) infection together with associated immune escape mechanisms are to a great degree understood. Due to a limited RNA expression and lacking a convincing evidence for production of virus proteins during latency, HSV in latently infected neurons had been for a long period considered invisible to immune system. This review analyzes currently accumulating data indicating an important role of immune response to HSV-1 latency and/or to early steps of HSV-1 reactivation process. Although this review focuses on HSV-1, it is likely that general concepts apply to both HSV-1 and HSV-2, since they share a great deal of similarity in their biological features including a high degree of sequence similarity at the nucleic acid level.     

Herpes simplex virus infection and apoptosis

Consequences of human herpes simplex virus (HSV) infection include the induction of apoptosis and the concomitant synthesis of proteins which act to block this process from killing the infected cell. Recent data has clarified our current understanding of the mechanisms of induction and prevention of apoptosis by HSV. These findings emphasize the fact that modulation of apoptosis by HSV during infection is a multicomponent phenomenon. We review recent evidence showing how this important human pathogen modulates the fundamental cell death process.     

Rabies and Herpes simplex virus encephalitis

Summary A retrospective study on the frequency, site and distribution of rabies and Herpes simplex virus (HSV) type 1 antigens by means of immunofluorescence (IF) and immunoperoxidase (IP) techniques was performed on routinely processed (formol-fixed, paraffin-embedded) brain autopsy material stored for up to 25 years. In 2 animal and 2 human rabies cases, inclusion bodies in neuronal cytoplasm and processes were brilliantly stained for rabies antigens by IF but were much less prominent or absent in usual histological stains. In 33 cases of histopathologically diagnosed necrotizing encephalitis, HSV antigens were demonstrated in 18 of 26 acute cases; 7 subacute cases (course longer than 4 weeks) were all negative for HSV antigens. Neuronal cytoplasm and nuclear membranes were the main sites of HSV antigens; nuclear inclusion bodies were inconstantly stained. Since most of HSV antigen negative cases also showed intranuclear inclusion bodies in HE stains, such nuclear inclusions are no reliable criterion for an HSV aetiology. On the other hand, their absence does not rule out a herpetic aetiology, but such a constellation is rare (only one of 18 HSV positive cases). Distribution of cells showing a positive reaction for HSV antigens may be patchy and irregular; therefore, a false negative result must be expected if very small tissue samples are examined (e.g, in needle biopsies from temporal lobe). In the leptomeninges, HSV antigen positive cells were found inconstantly and only in small numbers; this finding makes unlikely the possibility of an intravital diagnosis of HSV encephalitis by immunostaining of cerebrospinal fluid (CSF) cell preparations. Both immunohistological techniques applied in this study (IF and IP) gave the same results. Imprint preparations are useful when quick diagnosis is necessary.Immunohistological investigations are a simple and effective means to demonstrate a viral aetiology even in routinely processed material; the use of such material rules out hazards in laboratories which are not designed to handle highly infectious fresh material.     

Herpes simplex virus and toll-like receptors

The earliest interactions between viruses and host cells are critical to determining the outcome of infections. The interactions between a virus and its host cells that lead to the production of inflammatory cytokines are essential to the development of T cells and antibodies that provide long-term defense against the invaders. At the same time, however, these same cytokines (or sometimes other mediators or chemokines) stimulate inflammation, which may lead to localized tissue damage and/or systemic circulatory collapse and death. This review focuses on the interaction between Toll-like receptors, a critical component of the innate immune system of mammals, and their role in herpes simplex pathogenesis and immunity.     

Protective effect of an oral infection with Herpes simplex virus type 1 against subsequent genital infection with Herpes simplex virus type 2

The problem of whether oral Herpes simplex virus type 1 (HSV-1) infection provides protection against subsequent genital infection by Herpes simplex virus type 2 (HSV-2) was investigated. Mice were used as models. Following conditions in man, both the oral and genital infections applied were noninjurious. Mice infected orally with HSV-1 were weakly protected against virus take following vaginal challenge with HSV-2. Genital takes were found in 67% of the immunized mice, as compared with 83% of the controls (protection rate 20%,P=0.002). The course of genital infection in the immunized mice, however, was relatively mild: Lethality decreased from 97% in the controls to 35% in the immunized mice (protection rate 63%,P<0.001). Furthermore, local and neurologic symptoms occurred less frequently. Attempts to isolate the virus from homogenized brain and spinal cord of immunized mice that died after genital challenge with HSV-2 failed in most cases. Also virus could not be recovered from the liver of infected mice, irrespective of the experimental group.     

A case of fulminant herpes simplex hepatitis in an adult

The case presented documents HSV hepatitis in a 41 year old caucasian male with a history of prolonged steroid treatment and recent irradiation for brain tumor recurrence. The fulminant nature of the hepatitis, accompanied by gastric ulcer hemorrhage, lead to his death within 24 hours of symptomatic manifestation. The diagnosis of HSV hepatitis was made postmortem. The etiology of the hepatitis was established by light microscopic identification of Cowdry type A intranuclear inclusion bodies, electron microscopic identification of virus particles, and the immunohistochemical detection of herpes simplex virus antigens.     

Recovery from herpes simplex virus type-1 hepatitis in a female adult

Summary A study of one case of herpes simplex hepatitis in an adult woman is presented. The clinical feature and laboratory findings were typical for acute hepatitis in a febrile patient without herpetic mucocutaneous lesions. The evidence of high IgM antibody titer in serum against herpes simplex virus and confirmation of the herpes simplex virus hepatitis by immunofluorescent microscopy after liver biopsy helped us establish the diagnosis. After 3-months the patient recovered.Abbreviations HSV Herpes simplex virus - CMV Cytomegalovirus - EBV Epstein Barr virus