HHV8-related diseases in solid organ transplantation: a case series and systematic literature review

Abstract

Background: The true burden of HHV-8 in solid organ transplant (SOT) setting remains difficult to quantify and there are several uncertainties about the best prevention and management of HHV-8 related complications.

Objectives: To describe epidemiology and impact on outcome of HHV-8 related diseases in patients undergoing SOT, we reviewed all episodes diagnosed at our hospital over 8-year period and performed a narrative systematic literature review.

Sources: A search on PubMed, Scopus and Cochrane Library, according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, was done. All types of studies, published in any language from January 2000 to January 2025, focused on HHV-8 related diseases in adult and paediatric SOT recipients were considered. Due to heterogeneity among studies, the evidence synthesis was descriptive.

Content: Ninety-one studies conducted across 26 countries were included. Overall, 337 HHV-8 cases were reported among 19,283 transplant recipients, including 215 (63.8%) kidney, 80 (23.7%) liver, 22 (6.5%) lung, 13 (3.9%) heart and 5 (1.5%) combined transplants. Considering only cohort studies, a prevalence of 1.1% was estimated. The median time from transplant to disease was 11 months. For cases with available data, mismatch D+/R- was common (41/63, 65.1%). Main diseases included cutaneous Kaposi Sarcoma (KS) (49.7%) and visceral KS (33.4%), Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS) accounted for 4.7%. Management of immunosuppressive regimens mostly consisted in in reduction of maintenance regimen (169/209, 80.9%) and switch from tacrolimus to mTOR (79/209, 37.9%). Twenty-five studies reported antiviral use in 48/70 (68.6%) patients consisting in ganciclovir/valganciclovir (21 cases), foscarnet (17 cases) and/or cidofovir (10 cases). Rituximab was used for both oncological and non-oncological HHV-8 related diseases. Overall, 90-day mortality was 19.7%, reaching 29% excluding cutaneous KS.

Implications: HHV-8 related diseases after SOT are relatively uncommon, but associated with high mortality rates. Standardized management protocols for HHV-8 diseases are needed.