Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection

• Published in: Digestive diseases and sciences Vol. 63; no. 5; pp. 1237 - 1242
• Main Authors: Hu, Ke-Qin, Cui, Wei
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2018; Springer; Springer Nature B.V
• Subjects: Analysis; Antigens; Biochemistry; Care and treatment; Denaturation; Enzymes; Gastroenterology; Health aspects; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatology; Infection; Infections; Interferon; Liver cirrhosis; Medical colleges; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Oncology; Original Article; Proteins; RNA; Transplant Surgery; HCV immune complexes (HCV ICs); HCV core antigen (HCVcAg); Hepatitis C virus antigens (HCV-Ags); Hepatitis C virus (HCV); HCV infection
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-018-4968-9

Background Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. Methods Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP–WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. Results Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. Conclusions Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.