Detection of Residual HCV RNA in Patients Who Have Achieved Sustained Virological Response Is Associated with Persistent Histological Abnormality

Abstract

Background: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. Methods: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous recovery, were subjected to detect HCV-RNA in hepatocytes and PBMC. Paired liver biopsies at baseline and post-SVR were analyzed. Results: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = 0.022) and fibrosis regression (P = 0.015). Conclusions: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients albeit achieving serum resolution of hepatitis C and associated with persistent histological abnormality. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (NNSFC) (No. 81673654) (to J.Zhao); NNSFC (No. 31770186) (to Y. Wang); NNSFC (No. 81802020) (to Y. Wang); and the National S&T Major Project for Infectious Diseases (No. 2017ZX10302201001007) (to J.Zhao). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was done in accordance with the ethical principles of the Declaration of Helsinki as revised in 2013 and was approved by the Ethics Committee by each institution’s human research committee, Peking University People’s Hospital, the first Hospital of Jilin University and Chinese PLA General Hospital. Informed consent was obtained from all participants prior to enrolment. Written informed consent was received from participants prior to inclusion in the study.