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The Hepatitis C Virus-Induced Membranous Web in Liver Tissue
Open AccessArticle

Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA
Viral Infection and Immunity Unit, National Center of Microbiology, Health Institute Carlos III, 28220 Madrid, Spain
Infectious Disease/HIV Unit, Gregorio Marañón G. University Hospital, 28007 Madrid, Spain
Gregorio Marañón Health Research Institute, 28007 Madrid, Spain
HIV Unit, Internal Medicine Service, La Paz University Hospital, 28046 Madrid, Spain
La Paz Hospital Health Research Institute, 28046 Madrid, Spain
Santa Creu i Sant Pau Hospital, 08041 Barcelona, Spain
Infectious Disease Unit, Internal Medicine Department, Vigo University Hospital Complex, Galicia Sur Health Research Institute, 36312 Vigo, Pontevedra, Spain
Ramón y Cajal University Hospital, 28034 Madrid, Spain
Príncipe de Asturias University Hospital, 28805 Madrid, Spain
Laboratory Platform, Gregorio Marañón G. University Hospital, 28007 Madrid, Spain
Bioengineering, Biomaterials and Nanomedicine Networking Biomedical Research Center (CIBER-BBN), Health Institute Carlos III, 28029 Madrid, Spain
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Membership of the GESIDA 3603b Study Group is provided in the Appendix A.
Cells 2018, 7(11), 196;
Received: 18 August 2018 / Revised: 21 October 2018 / Accepted: 31 October 2018 / Published: 2 November 2018
(This article belongs to the Special Issue Hepatitis C Virus and Host Interactions)
Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4+ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4+ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response. View Full-Text
Keywords: chronic hepatitis C; HIV; cirrhosis; Treg cells; cytokines; immune dysfunction chronic hepatitis C; HIV; cirrhosis; Treg cells; cytokines; immune dysfunction
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Garcia-Broncano, P.; Medrano, L.M.; Berenguer, J.; González-García, J.; Jiménez-Sousa, M.Á.; Carrero, A.; Hontañón, V.; Guardiola, J.M.; Crespo, M.; Quereda, C.; Sanz, J.; García-Gómez, A.B.; Jimenez, J.L.; Resino, S.; The GESIDA 3603b Study Group. Dysregulation of the Immune System in HIV/HCV-Coinfected Patients According to Liver Stiffness Status. Cells 2018, 7, 196.

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