Herpes simplex virus hepatitis after solid organ transplantation in adults

Abstract

Twelve patients developed herpes simplex (HSV) hepatitis a median of 18 days after solid organ transplantation. This is earlier than cytomegalovirus hepatitis, which usually occurs 30-40 days after transplantation. Eight recipients (67%) died, and in seven, the diagnosis was made at autopsy or <48 h before death. Clinical manifestations associated with mortality were hypotension, disseminated intravascular coagulation (DIC), metabolic acidosis, gastrointestinal bleeding, and bacteremia. Laboratory abnormalities at diagnosis associated with mortality were high creatinine, low platelet counts, prolonged partial thromboplastin time, and a high percentage of band forms on the blood smear. Disseminated HSV disease was noted in four of six patients who had an autopsy and included involvement of lungs in three and the gastrointestinal tract in three. Five recipients developed DIC and all died. Pathologically, HSV hepatitis has two forms, focal and diffuse. All three patients with diffuse liver pathology died. However, three of seven with focal liver pathology survived with antiviral therapy, which suggests that early diagnosis and treatment may be lifesaving. None of these patients had received prophylactic acyclovir. It is possible that acyclovir prophylaxis may be able to prevent this disease. Herpes simplex virus (HSV) hepatitis is considered rare Materials and Methods Definitions. Cases of HSV hepatitis were diagnosed by laboratory, histologic, and clinical findings of one or more of the following in liver tissue from a biopsy or autopsy: isolation of HSV, positive immunoperoxidase staining for HSV antigen, or histology showing intranuclear inclusion bodies and pathology consistent with HSV lesions. In one case there was no liver tissue to examine, and the diagnosis was made by isolation of HSV from multiple sites outside the liver, including buffy coat, and clinical evidence of fulminant hepatitis. The histologic pattern of liver involvement with HSV was used to classify hepatitis as focal or diffuse. Disseminated HSV disease was defined as involvement of two or more organs discovered at autopsy. Involvement of skin confined to the oral or genital areas alone was not considered to represent dissemination. Disseminated intravascular coagulation (DIC) was defined by clinical evidence of bleeding from multiple sites, thrombocytopenia, and prolongation of prothrombin time (PT) and partial thromboplastin time (PTT). Laboratory methods. Tissue specimens obtained by biopsy or at autopsy were examined after routine staining and processing for detection of HSV antigen by immunoperoxidase staining and, on occasion, processed for isolation of HSV. Other specimens obtained from transplant recipients for viral isolation included throat wash, urine, buffy coat, bronchial secretions, and tissue. Specimens were inoculated onto tube monolayers of human embryonic kidney cells and observed for cytopathic effect typical of HSV. In some cases, the viral isolates were typed by direct immunofluorescence with monoclonal antibodies specific for HSV-I and HSV-2 (Syva; Genetic Systems, Seattle). When available, sera from recipients and donors were assayed for neutralizing antibody against HSV or for specific antibody against HSV-l or HSV-2 using the type-specific glycoproteins gGl and gG2 in an immunodot test adapted from methods described elsewhere Statistical analysis. The x 2 test was used for analysis of proportional differences between dichotomous variables. Results Case identification. Cases were identified by computer search for HSV isolates in liver tissue from either biopsies or autopsies from the virology laboratory and by search of pathology records for HSV hepatitis. As shown in table 1, the liver biopsy or autopsy specimens in 10 of 11 cases stained positive for HSV by immunoperoxidase; intranuclear inclu