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PLoS One. 2017 Jun 14;12(6):e0179094. doi: 10.1371/journal.pone.0179094. eCollection 2017.

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

Lee JW1,2, Kim W3, Kwon EK1,2, Kim Y1,2, Shin HM2, Kim DH1,2, Min CK1,2, Choi JY2,4, Lee WW1,2,4, Choi MS1,5, Kim BG3, Cho NH1,2,5.

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Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.


Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

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