Immune Dynamics of HHV-8 Infection After Liver Transplantation: From Viremia to KICS and Kaposi’s Sarcoma

Liver transplant recipients are susceptible to the reactivation of latent viruses due to chronic immunosuppression. Among these, human herpesvirus 8 (HHV-8) poses a significant clinical threat, particularly in endemic areas, where seroprevalence remains high. Post-transplant HHV-8 reactivation may lead to a spectrum of manifestations ranging from asymptomatic viremia to Kaposi’s Sarcoma (KS) and, more severely, Kaposi’s Sarcoma Inflammatory Cytokine Syndrome (KICS), a condition associated with high morbidity and mortality. In our single-centre retrospective study, we examined 14 HHV-8-infected transplant patients, including several liver transplant recipients, and categorized them into three distinct clinical groups: asymptomatic viremia (n=5), classic or disseminated KS (n=4), and KICS (n=5). Comprehensive immuno-virological profiling was performed, including longitudinal monitoring of HHV-8 viral load, Specific T-cell response, and cytokine panels. Our findings underscore the critical importance of immune control in liver transplant recipients. Patients with asymptomatic viremia, including liver recipients, exhibited robust HHV-8-specific T-cell responses and preserved T-cell function, along with controlled cytokine levels. In contrast, those progressing to KS and especially KICS showed increasing T-cell exhaustion (notably elevated PD-1 expression), reduced HHV-8-specific reactivity, and marked elevations in inflammatory cytokines (IL-6, IL-10, IFN-α). Importantly, all KICS cases had undergone liver transplantation, and disease progression was preceded by rising HHV-8 viremia and a dysregulated inflammatory response. These results point to a unique vulnerability of liver transplant recipients to immune escape and cytokine-driven pathology in the context of HHV-8 primary infection or reactivation. This study highlights the need for early and tailored viro-immunological monitoring in liver transplant patients with HHV-8 infection. By identifying immune exhaustion markers and cytokine profiles early, clinicians may improve patient outcomes through timely immunosuppression adjustment and antiviral or immunomodulatory interventions. Further research is needed to define optimal strategies for surveillance and intervention in this high-risk population.