Persistence of Circulating Hepatitis C Virus Antigens-Specific Immune Complexes in Patients with Resolved HCV Infection
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.
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.
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.
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.
KeywordsHepatitis C virus (HCV) HCV infection Hepatitis C virus antigens (HCV-Ags) HCV core antigen (HCVcAg) HCV immune complexes (HCV ICs)
Hepatitis C virus
Chronic hepatitis C
Sustained virologic response
Viremic HCV infection
Resolved HCV infection
- HCV RNA RT-PCR
HCV RNA reverse transcription polymerase chain reaction
HCV core antigen
- HCV-Ags EIA, or EIA
HCV antigens enzyme immunoassay
Immunoprecipitation and Western blot assays
The authors thank John M. Vierling., M.D., for discussion about data interpretation and critical review of the manuscript.
KQH conceived the concept of the entire present study, searched the literature, designed study, analyzed and interpreted the data, and led manuscript writing. WC participated in literature search, performed the experiments, analyzed data, and was involved in manuscript preparation.
This was an institutionally supported investigator-initiated study. There was no external funding.
Compliance with ethical standards
Conflict of interest
Dr. Hu is on the speakers’ bureau for Abbvie, Gilead Sciences Inc., and Merck, and consultant for DiligenMed, Inc. Dr. Cui has no disclosure.
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