Kazan medical journalKazan medical journal0368-48142587-9359Eco-Vector1029810.17816/KMJ2018-760Research ArticleClinical and immunological characteristics of patients with chronic hepatitis C during antiviral therapy in interferon-free regimenBasinaV Vv.basina@mail.ruSukhorukA Av.basina@mail.ruArsentievaN Av.basina@mail.ruLyubimovaN Ev.basina@mail.ruSemenovA Vv.basina@mail.ruEsaulenkoE Vv.basina@mail.ruTotolyanA Av.basina@mail.ruSaint Petersburg State Pediatric Medical UniversitySaint-Petersburg Pasteur Research Institute of Epidemiology and Mictobiology1010201899576076510102018Copyright © 2018, Basina V.V., Sukhoruk A.A., Arsentieva N.A., Lyubimova N.E., Semenov A.V., Esaulenko E.V., Totolyan A.A.2018<p><strong>Aim.</strong> To study the biomarkers of liver inflammation that occur during antiviral therapy in the interferon-free regimen.</p>
<p><strong>Methods.</strong> 14 patients were examined during antiviral therapy of chronic viral hepatitis C genotype 1. Treatment with dasabuvir, ombitasvir, paritaprevir and ritonavir for 12 weeks was received by 8 patients. Daklatasvir and asunaprevir was administered to 6 patients for 24 weeks. 11 patients had the concentrations of cytokines/chemokines (TNF, CCL2/MCP-1, CCL20/MIP-3, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) measured in the blood plasma by multiplex analysis. In six patients, the content of CXCR3+ and CCR6+ receptors in different subpopulations of lymphocytes was determined by flow cytofluorimetry. Patients were divided into 2 groups: without liver fibrosis and with severe fibrosis.</p>
<p><strong>Results.</strong> 100% demonstrated virologic response. In both groups, significant reduction of CXCL10/IP-10 concentration was found in the patients at the end of treatment compared to pre-therapy (p=0.025 and 0.00015, respectively). In the first group a tendency to increase of the relative content of T-lymphocytes (p=0.065) was observed, and in the second group, a significant increase of the relative content of TNKCCR6+ (p=0.02) was observed.</p>
<p><strong>Conclusion.</strong> Chemokine CXCL10/IP-10 is a biomarker characterizing the decrease of liver inflammation during therapy and not depending on the degree of liver fibrosis. The tendency to increase of the relative content of T lymphocytes in the first group and a significant increase in TNKCCR6+ cells during treatment in the second group may play an important role in eliminating hepatitis C virus.</p>CXCL10/IP-10hepatitis Cantiviral therapyinterferon-free regimenchemokinesCXCL10/IP-10fibrosisгепатит Спротивовирусная терапиябезинтерфероновый режимхемокиныфиброз[World Health Organization. Hepatitis C. Key facts. http://www.who.int/news-room/fact-sheets/detail/hepatitis-c (access date: 18.06.18).][Angeli P., Bernardi M., Villanueva C. et al. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of patients with decompensated cirrhosis. J. Hepatol. 2018; 69 (2): 406–460. DOI: 10.1016/j.jhep.2018.03.024.][Esaulenko E.V., Vysochinskaya V.V., Nikitina O.E. The effectiveness of combined antiviral therapy in patients with chronic hepatitis C, 1B genotype with various degrees of fibrosis. Zhurnal infektologii. 2012; 4 (3S): 75. (In Russ.)][Maevskaya M.V., Ivashkin V.T., Znojko O.O. at el. Efficacy and safety of the national inhibitor of Narlaprevir protease in primary and previously treated patients with chronic hepatitis C caused by the 1st genotype virus, without liver cirrhosis (results of the Pioneer study). Rossijskij zhurnal gastroehnterologii, gepatologii, koloproktologii. 2017; 27 (6): 41–51 (In Russ.)][Ivashkin V.T., Maevskaya M.V., Аbdurakhmanov D.T. et al. Modern possibilities of antiviral therapy using Daclatasvir in the treatment of patients with chronic viral hepatitis C: results of the individual access program. Rossijskij zhurnal gastroehnterologii, gepatologii, koloprotologii. 2017; 27 (6): 52–62. (In Russ.)][Lin J.C., Habersetzer F., Rodriguez-Torres M. et al. Interferon γ-induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: implications for the innate immune response. J. Infect. Dis. 2014; 210 (12): 881–885. DOI: 10.1093/infdis/jiu325.][Bility M.T., Nio K., Li F. et al. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation. Sci. Rep. 2016; (6): 39520. DOI: 10.1038/srep39520.][Kazankov K., Barrera F., Moller H.J. et al. Soluble CD163, a macrophage activation marker, is independently associated with fibrosis in patients with chronic viral hepatitis B and C. Hepatology. 2014; 60 (2): 521–530. DOI: 10.1002/hep.27129.][Sandler N.G., Koh C., Roque A. et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology. 2011; 141 (4): 1220–1230. DOI: 10.1053/j.gastro.2011.06.063.][Askarieh G., Alsio A., Pugnale P. et al. Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C. Hepatology. 2010; 51: 1523–1530. DOI: 10.1002/hep.23509.][Prinapori R., Sticchi L., Alicino C. et al. Role of HCV-RNA decay and IP-10 levels after 48 hours of standard HCV therapy as predictors of rapid virological response. Clin. Res. Hepatol. Gastroenterol. 2015; 39: 705–710. DOI: 10.1016/j.clinre.2015.04.001.][Mascia C., Vita S., Zuccalà P. et al. Changes in inflammatory biomarkers in HCV infected patients undergoing direct acting antiviral-containing regimens with or without interferon. PLoS ONE. 2017; 12 (6): e0179400. DOI: 10.1371/journal.pone.0179400.][Serti E., Chepa-Lotrea X., Kim Y. J. et al. Successful Interferon-Free Therapy of Chronic Hepatitis C Virus Infection Normalizes Natural Killer Cell Function. Gastroenterology. 2015; 149 (1): 190–200. DOI: 10.1053/j.gastro.2015.03.004.][Diago C. M., Castellano G., GarcoAa-Samaniego J. et al. Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis. Gut. 2006; 55 (3): 374–379. DOI: 10.1136/gut.2005.074062.]