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Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

Deciphering the Significance of Plasma Chemokines as Prognostic Biomarkers in Pegylated IFN-Α-2a /Ribavirin-Treated Chronic Hepatitis C Genotype 4 Patients

Author(s): M. Haroon Hamed, Peter Natesan Pushparaj, Shafiqur Rehman, Saleh Al-Karim, Salem Bazarah and Ishtiaq Qadri*

Volume 22, Issue 5, 2022

Published on: 26 April, 2022

Article ID: e030322201654 Pages: 5

DOI: 10.2174/1871526522666220303142837

Abstract

Background: Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective.

Objectives: Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy.

Methods: Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA).

Results: A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy.

Conclusion: Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma.

Limitations: Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Keywords: HCV, antiviral treatment, SVR, cytokines, plasma chemokines, prognostic biomarkers.

Graphical Abstract
[1]
Li HC, Lo SY. Hepatitis C virus: Virology, diagnosis and treatment. World J Hepatol 2015; 7(10): 1377-89.
[http://dx.doi.org/10.4254/wjh.v7.i10.1377] [PMID: 26052383]
[2]
Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011; 17(2): 107-15.
[http://dx.doi.org/10.1111/j.1469-0691.2010.03432.x] [PMID: 21091831]
[3]
Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013; 57(4): 1333-42.
[http://dx.doi.org/10.1002/hep.26141] [PMID: 23172780]
[4]
Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.
[http://dx.doi.org/10.1016/S0140-6736(12)61728-0] [PMID: 23245604]
[5]
Fierro NA, Gonzalez-Aldaco K, Torres-Valadez R, Martinez-Lopez E, Roman S, Panduro A. Immunologic, metabolic and genetic factors in hepatitis C virus infection. World J Gastroenterol 2014; 20(13): 3443-56.
[http://dx.doi.org/10.3748/wjg.v20.i13.3443] [PMID: 24707127]
[6]
Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006; 354(6): 610-21.
[http://dx.doi.org/10.1056/NEJMra052723] [PMID: 16467548]
[7]
Brass A, Brenndörfer ED. The role of chemokines in hepatitis C virus-mediated liver disease. Int J Mol Sci 2014; 15(3): 4747-79.
[http://dx.doi.org/10.3390/ijms15034747] [PMID: 24646914]
[8]
Fahey S, Dempsey E, Long A. The role of chemokines in acute and chronic hepatitis C infection. Cell Mol Immunol 2014; 11(1): 25-40.
[http://dx.doi.org/10.1038/cmi.2013.37] [PMID: 23954947]
[9]
Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol 2013; 10(9): 553-62.
[http://dx.doi.org/10.1038/nrgastro.2013.107] [PMID: 23817321]
[10]
Abd-Elsalam S, Badawi R, Elnawasany S, et al. Sofosbuvir, pegylated interferon and ribavirin in the treatment of an Egyptian cohort with hepatitis C virus infection in real-life clinical practice. Infect Disord Drug Targets 2019; 19(2): 179-84.
[PMID: 30207250]
[11]
Meissner EG, Wu D, Osinusi A, et al. Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome. J Clin Invest 2014; 124(8): 3352-63.
[http://dx.doi.org/10.1172/JCI75938] [PMID: 24983321]
[12]
Amal MA, Naglaa E-TR, Ebada SM, et al. Hepatitis C virus: Efficacy of new DAAs regimen. Infect Disord Drug Targets 2020; 20(2): 143-9.
[PMID: 30663575]
[13]
Hanafy AS, Soliman S, Abd-Elsalam S. Rescue therapy for chronic hepatitis C virus infection after repeated treatment failures: Impact on disease progression and risk of hepatocellular carcinoma. Hepatol Res 2019; 49(4): 377-84.
[http://dx.doi.org/10.1111/hepr.13303] [PMID: 30570817]
[14]
Soliman H, Ziada D, Salama M, et al. Predictors for fibrosis regression in chronic HCV patients after the treatment with DAAS: Results of a real-world cohort study. Endocr Metab Immune Disord Drug Targets 2020; 20(1): 104-11.
[http://dx.doi.org/10.2174/1871530319666190826150344] [PMID: 31448717]
[15]
Ashrafi Hafez A, Ahmadi Vasmehjani A, Baharlou R, et al. Analytical assessment of interleukin - 23 and -27 cytokines in healthy people and patients with hepatitis C virus infection (genotypes 1 and 3a). Hepat Mon 2014; 14(9): e21000.
[http://dx.doi.org/10.5812/hepatmon.21000] [PMID: 25386199]
[16]
Amoras EDSG, Monteiro Gomes ST, Freitas Queiroz MA, et al. Intrahepatic interleukin 10 expression modulates fibrinogenesis during chronic HCV infection. PLoS One 2020; 15(10): e0241199.
[http://dx.doi.org/10.1371/journal.pone.0241199] [PMID: 33125400]
[17]
Wasmuth HE, Tacke F, Trautwein C. Chemokines in liver inflammation and fibrosis. Semin Liver Dis 2010; 30(3): 215-25.
[http://dx.doi.org/10.1055/s-0030-1255351] [PMID: 20665374]
[18]
Cao S, Liu M, Sehrawat TS, Shah VH. Regulation and functional roles of chemokines in liver diseases. Nat Rev Gastroenterol Hepatol 2021; 18(9): 630-47.
[http://dx.doi.org/10.1038/s41575-021-00444-2] [PMID: 33976393]
[19]
Wasmuth HE, Lammert F, Zaldivar MM, et al. Antifibrotic effects of CXCL9 and its receptor CXCR3 in livers of mice and humans. Gastroenterology 2009; 137(1): 309-19.
[http://dx.doi.org/10.1053/j.gastro.2009.03.053]
[20]
Lee IC, Huang YH, Su CW, et al. CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy: A pilot study. PLoS One 2013; 8(10): e76798.
[http://dx.doi.org/10.1371/journal.pone.0076798] [PMID: 24124595]
[21]
Vargas A, Berenguer J, Catalán P, et al. Association between plasma levels of eotaxin (CCL-11) and treatment response to interferon-alpha and ribavirin in HIV/HCV co-infected patients. J Antimicrob Chemother 2010; 65(2): 303-6.
[http://dx.doi.org/10.1093/jac/dkp454] [PMID: 20016018]
[22]
Jabłońska J, Pawłowski T, Laskus T, et al. The correlation between pretreatment cytokine expression patterns in peripheral blood mononuclear cells with chronic hepatitis C outcome. BMC Infect Dis 2015; 15(1): 556.
[http://dx.doi.org/10.1186/s12879-015-1305-1] [PMID: 26637466]
[23]
Hoshida Y, Kato N, Yoshida H, et al. Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8. J Infect Dis 2005; 192(2): 266-75.
[http://dx.doi.org/10.1086/430924] [PMID: 15962221]
[24]
Ramm GA, Shepherd RW, Hoskins AC, et al. Fibrogenesis in pediatric cholestatic liver disease: Role of taurocholate and hepatocyte-derived monocyte chemotaxis protein-1 in hepatic stellate cell recruitment. Hepatology 2009; 49(2): 533-44.
[http://dx.doi.org/10.1002/hep.22637] [PMID: 19115220]
[25]
Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 2007; 13(11): 1324-32.
[http://dx.doi.org/10.1038/nm1663] [PMID: 17952090]
[26]
Kruglov EA, Nathanson RA, Nguyen T, Dranoff JA. Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts. Am J Physiol Gastrointest Liver Physiol 2006; 290(4): G765-71.
[http://dx.doi.org/10.1152/ajpgi.00308.2005] [PMID: 16282363]
[27]
Singh S, Anshita D, Ravichandiran V. MCP-1: Function, regulation, and involvement in disease. Int Immunopharmacol 2021; 101(Pt B): 107598.
[http://dx.doi.org/10.1016/j.intimp.2021.107598] [PMID: 34233864]
[28]
Zhdanov KV, Gusev DA. Chirskiĭ VS, et al. Chronic HCV-infection and expression of mRNA of CC-chemokines and their receptors. Zh Mikrobiol Epidemiol Immunobiol 2008; (4): 73-8.
[PMID: 18822499]
[29]
Asselah T, Bièche I, Laurendeau I, et al. Liver gene expression signature of mild fibrosis in patients with chronic hepatitis C. Gastroenterology 2005; 129(6): 2064-75.
[http://dx.doi.org/10.1053/j.gastro.2005.09.010] [PMID: 16344072]
[30]
Bigger CB, Guerra B, Brasky KM, et al. Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees. J Virol 2004; 78(24): 13779-92.
[http://dx.doi.org/10.1128/JVI.78.24.13779-13792.2004] [PMID: 15564486]

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