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Background and Aim: To observe the clinical value of hepatitis C virus (HCV) core antigen (HCcAg) levels in monitoring acute HCV infection in patients with spontaneous clearance (SC) or clearance induced by antiviral therapy., Methods: Patients with iatrogenic HCV infection (n = 104) were enrolled at the Shengjing Hospital, China Medical University, between 5 February 2013 and 3 April 2013. All cases were diagnosed with acute HCV infection, enrolled within 90 days of infection, and followed for 12 to 16 weeks. Blood was collected every month. HCV RNA and HCcAg levels were detected. From week 16, patients without SC were treated with pegylated-interferon and the HCV RNA and HCcAg levels were observed monthly. Follow-up was 7.5 (5.0 to 10.4) months. The Spearman correlation analysis was performed to determine the correlation between HCV RNA and HCcAg. Logistic regression analysis was used to determine the association of baseline HCV RNA and HCcAg levels with SC., Results: Ten patients (9.62%) showed SC, with a negative conversion time of 57 (14 to 143) days. During follow-up, HCV RNA and HCcAg expression levels were positively correlated for each patient (except on the sixth month), but the levels of HCV RNA and HCcAg were not associated with HCV infection SC., Conclusions: HCcAg levels could be of value for monitoring the course early HCV infection, but could not predict SC of HCV infection., (© 2018 Wiley Periodicals, Inc.)