Long-term virological follow up of patients with occult hepatitis C virus infection

Background: Patients with occult hepatitis C virus (HCV) infection (HCV-RNA in liver without detectable anti-HCV and serum HCV-RNA) may have viral RNA in peripheral blood mononuclear cells (PBMCs) and in serum after ultracentrifugation, and may present HCV-specific T-cell responses, but it is unknown whether these markers persist to be detectable over time. Aim: To perform a prospective virological long-term follow up of patients with occult HCV. Methods: Viral markers were tested every 3-4 months during 55.7 +/- 20.3 months in 37 patients with occult HCV who were under ursodeoxycholic acid treatment. Results: Viral RNA was detectable in PBMCs of 31 patients during the follow up. In 23 of them, viral RNA in PBMCs was detected intermittently and in the other eight patients HCV-RNA was positive in a single sample. After ultracentrifugation, serum HCV-RNA was detected in 33 patients, being the viraemia intermittently detectable in 28, whereas in the remaining five patients, serum HCV-RNA was positive only once. Only one patient tested always HCV-RNA negative in PBMCs and in ultracentrifuged serum during follow up. Specific Core, NS3, and/or NS4 T-cell responses were found in 31 of the patients. The patient who was always HCV-RNA negative in PBMCs and in ultracentrifuged serum had specific HCV-T-cell responses. Conclusions: Occult HCV infection persists over time with fluctuating viraemia levels that induce and maintain specific T-cell responses against viral proteins.