BackgroundHuman Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. MethodsThis cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. ResultsAnti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8%) and four healthy individuals (2.6%) (p=0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4%), followed by autoimmune hepatitis (13.1%) and virus-related cirrhosis (4.7%). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p=0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. ConclusionThe role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.