Primary and Reactivated HHV8 Infection and Disease After Liver Transplantation: A Prospective Study

Abstract

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

How I treat HHV8/KSHV-related diseases in posttransplant patients

“…72 In this clinical report, the patient presented with fever, mononucleosis-like symptoms and signs (as pharyngeal erythema, hepatosplenomegaly, weight loss, night sweats), pancytopenia, normal bone marrow with moderate plasmacytosis without hemophagocytosis, and high HHV8 viral loads detected in PBMCs, bone marrow, and pharyngeal specimens. 72 To date, acute hepatitis syndromes, characterized by fever, cutaneous rash, and elevated liver enzymes, have also been reported in several posttransplant patients, either during HHV8 reactivation after an autologous HSCT 73 or in concomitance with donor-derived primary HHV8 infections, after either liver SOT 61 or allogeneic HSCT (M.L., unpublished data, November 2008). The disease has revealed to be self-limiting in both the HSCT patients we observed.…”

“…Indeed, antiviral treatments alone (ie, cidofovir and ganciclovir) failed to control either the severe primary HHV8 infections in liver transplant patients, 33,61 or the aplastic syndrome after HHV8 reactivation in a renal recipient. 65 However, in our experience, foscarnet therapy alone for 2 weeks was associated with the complete resolution of a primary HHV8 infection syndrome, characterized by fever, severe pancytopenia and HPS, occurring after renal transplantation.…”

“…At opposite, in the 2 postliver transplant cases reported by Pietrosi et al, clinical presentations were more aggressive and challenging, being also associated with pleural and peritoneal effusions, and lethally evolving into multiorgan failures, despite cidofovir antiviral therapy. 61 …”

“…A delayed introduction of rituximab in this clinical context may result in a fatal outcome, which cannot be prevented by the sole use of antivirals. 61,65 …”

“…46 PT-MCD was diagnosed in 6 and 4 patients after either kidney or liver transplantation, respectively, showing a more favorable outcome compared with PT-PEL cases. [53][54][55][56][57][58][59][60][61][62] Of note, 1 liver recipient affected with systemic PT-MCD, associated with constitutional symptoms and high HHV8 viremia, was successfully treated with valgancyclovir and weaning of immunosuppressive therapy (cyclosporine withdrawal), without worsening of the graft functions. 62 Moreover, we have recently used rituximab to treat a case of PT-MCD occurring in a renal transplant patient, 10 years after transplantation, achieving a prolonged disease remission, with no adverse effects (M.L., P.B.…”