Temporal Association Between Increased Virus-Specific Th17 Response and Spontaneous Recovery From Recurrent Hepatitis C in a Liver Transplant Recipient

Abstract

Spontaneous clearance of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) is a rare occurrence. Here, we present detailed immunological analysis of an interferon naive OLT recipient receiving uninterrupted immunosuppression who cleared HCV spontaneously 2 years after transplantation. Enzyme-linked immunospot assay analysis of peripheral T-cell interferon gamma (IFN-γ), interleukin (IL)-10, and IL-17 response to HCV core and nonstructural antigen 4 and enzyme-linked immunosorbent assay (ELISA) to collagen (Col) subtypes I, II, IV, and V were performed in the index patient at the time of viral clearance and compared with an OLT cohort with persistent viremia matched for time from OLT, immunosuppression, and histology. Enzyme-linked immunospot assay and ELISA analysis were repeated on the patient 4 years after OLT. Transcription-mediated amplification assays were used to confirm viral clearance. Compared with a cohort of post-OLT and nontransplanted viremic HCV patients, the index patient with HCV clearance demonstrated higher IL-17, IL-10, and lower IFN-γ response to nonstructural antigen 4 and core antigen and a higher titer of antibodies (Abs) to Col subtypes I, II, and V during clearance. On follow-up 2 years later, HCV-specific IFN-γ was increased in the index patient, with a decline in IL-17 and IL-10 response and Col I, II, and V Ab titer. Virus-induced activation of Th-17 cells may contribute to HCV clearance post-OLT. Maintenance of viral suppression may be facilitated by restoration of Th1 (IFN-γ) responses. Modulation of Th17 immunity deserves further attention as a therapeutic strategy in the treatment of HCV recurrence post-OLT.