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Background: An outbreak of severe respiratory illness caused by a novel coronaviruses (2019- nCoV) in China since December 2019 This work aim to evaluate the c

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.

Background: Direct-acting antiviral agents (DAAs) have opened a new era for treating chronic hepatitis C virus (HCV) infection. However, whether DAA induced SVR attains real cure and complete eradication of HCV RNA is unknown, because occult HCV infection (OCI), as defined the detection of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum of HCV RNA, may occur despite SVR and the clinical significance is yet to be established. We thus investigated the prevalence and provisional outcome of OCI in patients who achieved spontaneous or therapy-induced resolution of hepatitis C. Methods: Chronic HCV subjects from three tertiary hospitals who had achieved serum viral clearance, including 60 of DAAs treatment, 50 of pegylated interferon plus ribavirin (PR) treatment, and 30 of spontaneous recovery, were subjected to detect HCV RNA in hepatocytes by in suit hybridization as well as in PBMC by PCR. Liver function testes, HCV genotypes, and paired liver biopsies of pre- and post-treatment for each patient were acquired for comparison analysis. Findings: 16 of 140 subjects (11·4%) were found to have OCI, with the highest (15·0%) rate in DAA-based treated subjects, 10·0% in PR treated subjects and 6·7% in spontaneously resolved cases. Rates of OCI were 16·7% and 11·1% among patients with PR-free regimen and PR-based regimen, respectively. The existence of intermediate negative strand of HCV genome in all PBMCs of OCI patients suggested ongoing viral replication. The occurrence of OCI is more frequent in patients with genotype 3 HCV but less in patients with genotype 1. No correlation between baseline HCV viral load, interleukin-28B genotype, baseline transaminases, post transaminases and occurrence of OCI was found. While notably, OCI patients had more advanced liver fibrosis and active inflammation at both baseline and post- treatment. In addition, fibrosis scores were significantly decreased after SVR only in patients without OCI (P