Aim of the present study was to perform a comprehensive analysis if soluble CD81 is increased in patients with chronic hepatitis C compared to healthy controls, patients with chronic HCV infection but persistently normal alanine transaminase (ALT) levels, and patients with cured hepatitis C. Therefore, a method to quantify soluble CD81 in the exosomal serum fraction was established, and the association of soluble CD81 in the exosomal serum fraction with clinical and virological parameters within the different cohorts was investigated. This evidence concerns the gene CD81 and chronic hepatitis C virus infection.