Human Herpes Virus 8 in Solid Organ Transplantation

Abstract

Human herpes virus 8 (HHV-8) is a geographically limited virus that causes neoplastic and nonneoplastic diseases predominantly in endemic regions. Primary HHV-8 infection, which is usually asymptomatic in immunocompetent individuals, result in lifelong latency. When the equilibrium between virus and host immunity is disturbed, such as after organ transplantation, HHV-8 may activate molecular pathways that drive oncogenesis. Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease are the major malignancies associated with HHV-8. The incidences of these neoplastic pathologies mirror the geographic HHV-8 seroprevalence, and certain groups of patients are at higher risk. In this context, the risk of HHV-8 and its clinical disease is highest in immunocompromised patients, including transplant recipients. Solid organ transplant recipients from HHV-8 endemic regions may develop HHV-8 reactivation or primary infection and manifest with Kaposi's sarcoma or less commonly primary effusion lymphoma and Castleman's disease; these neoplastic diseases are reported much less commonly in low-prevalent areas. There is currently no standard method of screening for HHV-8 infection in the transplant setting, although HHV-8 polymerase chain reaction is available to confirm clinical suspicion of infection. Management of HHV-8-associated diseases entails primarily a reduction in the degree of pharmacologic immunosuppression and, in some cases, chemotherapy may be required. The mammalian target of rapamycin inhibitor sirolimus may have the potential for management because of its antiproliferative properties. The role of antiviral drugs for HHV-8 prevention and treatment is yet to be defined.

Human Herpesvirus 8–Related Primary Effusion Lymphoma After Liver Transplantation

“…HHV8 tends to be more common in equatorial areas with a seroprevalence greater than 50% in Africa and South America, intermediate prevalence between 5% and 20% in the Mediterranean region, Middle East, and the Caribbean, and low prevalence of less than 5% in North America, Northern Europe, and Asia (13). Men have a significantly higher seroprevalence than women in the same regions.…”

“…PEL primarily affects the severely immunocompromised, most notably those with HIV. A small number of cases have also been reported among those with malignancy, cirrhosis or organ transplantation (13,14). Unchecked proliferation of HHV8-infected cells is implicated in its development (9).…”

“…HHV8 is transmitted via saliva and to a lesser extent injection drug use, blood transfusions, and organ transplantation. In the United States, the highest risk population is HIVpositive men who have sex with men, where the seroprevalence is as high as 30% with a seroprevalence estimated at 15% among transplant patients (13). There is evidence that transmission of HHV8 via a solid organ graft can occur (14,16).…”

Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation

“…104 Kaposi Sarcoma-Associated Herpes Virus.-Kaposi sarcoma-associated herpes virus (HHV8) has variable prevalence around the globe, and the risk of primary or reactivated infection varies in parallel (highest in Africa, then the Mediterranean and South America, lowest in North America and Northern Europe). 129,143,144 At least 65 cases of transplant-associated Kaposi sarcoma have been reported to the Organ Procurement and Transplantation Network database (United Network for Organ Sharing, Richmond, Virginia), 143 and the incidence in patients with transplants has been calculated as 54-fold to 400-fold that of the general population, depending on local prevalence. 144 The HHV8 is associated with a variety of malignancies in patients with transplants and other immunosuppressed individuals, including Kaposi sarcoma (skin, lymph nodes, or viscera), and the less-common, primary effusion lymphoma and Castleman disease, among other rare associations.…”

“…144 The HHV8 is associated with a variety of malignancies in patients with transplants and other immunosuppressed individuals, including Kaposi sarcoma (skin, lymph nodes, or viscera), and the less-common, primary effusion lymphoma and Castleman disease, among other rare associations. 129,[143][144][145] Demonstration of HHV8 in tissue is an important diagnostic feature for these disease processes, making IHC an important part of the evaluation. In general, antibodies to the latency-associated nuclear antigen LANA1 are employed, with nuclear reactivity indicating a positive stain.…”