Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 8, 2017; 9(25): 1073-1080
Published online Sep 8, 2017. doi: 10.4254/wjh.v9.i25.1073
CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients
Natalia Laufer, Diego Ojeda, María Laura Polo, Ana Martinez, Héctor Pérez, Gabriela Turk, Pedro Cahn, Norberto Walter Zwirner, Jorge Quarleri
Natalia Laufer, Investigador Asistente - CONICET, Instituto Investigaciones Biomédicas en Retrovirus y SIDA INBIRS, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina
Natalia Laufer, Diego Ojeda, María Laura Polo, Gabriela Turk, Jorge Quarleri, Instituto INBIRS, UBA-CONICET, Buenos Aires C1121ABG, Argentina
Natalia Laufer, Ana Martinez, Héctor Pérez, Hospital Juan A Fernández, Buenos Aires C1121ABG, Argentina
Pedro Cahn, Fundación Huésped, Buenos Aires C1121ABG, Argentina
Norberto Walter Zwirner, Laboratorio de Fisiopatología de la Inmunidad, Innata Instituto de Biología y Medicina Experimental, Buenos Aires C1121ABG, Argentina
Norberto Walter Zwirner, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina
Author contributions: Laufer N, Turk G, Cahn P, Quarleri J and Zwirner NW contributed to study conception and design; Laufer N contributed to data acquisition, data analysis and interpretation, and writing of article; Pérez H, Martinez A, Ojeda D and Polo ML contributed to data acquisition, data analysis and interpretation; Laufer N, Turk G, Quarleri J, Cahn P and Zwirner NW contributed to editing, reviewing and final approval of article.
Institutional review board statement: The study was reviewed and approved by Bioethics Committee of Fundación Huésped (Buenos Aires, Argentina).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors do not have any commercial or other association that might pose a conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Natalia Laufer, MD, PhD, Investigador Asistente - CONICET, Instituto Investigaciones Biomédicas en Retrovirus y SIDA INBIRS, Universidad de Buenos Aires. Paraguay 2155 Piso 11, Buenos Aires C1121ABG, Argentina. nlaufer@fmed.uba.ar
Telephone: +54-11-45083689 Fax: +54-11-45083705
Received: January 4, 2017
Peer-review started: Janaury 7, 2017
First decision: April 6, 2017
Revised: April 29, 2017
Accepted: May 22, 2017
Article in press: May 24, 2017
Published online: September 8, 2017
Processing time: 245 Days and 7.6 Hours
Abstract
AIM

To characterize peripheral blood natural killer (NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients.

METHODS

Peripheral mononuclear cells from 24 HIV/HCV (HBV negative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: Anti-CD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), anti-NKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L (PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-FasL(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using FlowJo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.

RESULTS

Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was (6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls (G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1 (G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).

CONCLUSION

Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Keywords: CD4+ T cell; Human immunodeficiency virus/hepatitis C virus-coinfection; Fibrosis; Biomarker; Natural killer cells

Core tip: Approximately 2.3 million individuals with human immunodeficiency virus are coinfected with hepatitis C virus (HCV). The high cost of HCV treatment restricts its use. It is crucial to identify patients with advanced liver fibrosis with an urgent need of treatment. The aim of this study was to identify natural killer (NK) phenotypes as a biomarker for liver fibrosis. We observed that those subjects with higher fibrosis are those with lower percentage of NK cells and also with lower LTCD4+ count. These constitute two simple parameters that might be performed in a routine laboratory test and used in clinical practice as biomarkers for liver fibrosis.