4.7 Article

Association of cytokines with hepatitis B virus and its antigen

Journal

JOURNAL OF MEDICAL VIROLOGY
Volume 92, Issue 12, Pages 3426-3435

Publisher

WILEY
DOI: 10.1002/jmv.26301

Keywords

chronic hepatitis B; cytokines; HBeAg; HBsAg; HBV DNA

Categories

Funding

  1. National Science and Technology Major Project of China [2017ZX10201201-001-006, 2017ZX10201201-002-006, 2018ZX10715-005-003-005]
  2. Digestive Medical Coordinated Development Center of Beijing Hospitals Authority [XXZ0302, XXT28]
  3. Beijing Science and Technology Commission [D161100002716002]
  4. Beijing Hospitals Authority of Hospitals Clinical Medicine Development of Special Funding Support [XMLX 201706]

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To investigate the characteristics of cytokines in patients with different HBV infection status and their correlation with HBV DNA, HBsAg, and HBeAg levels. Peripheral blood samples were collected from patients with chronic HBV infection in immune tolerance phase (IT), HBeAg-positive chronic hepatitis B (CHB), and acute hepatitis B (AHB) groups, and levels of cytokines were detected by Luminex technique, and analyzed by FLEXMAP 3D analyzer. The correlation between cytokines and HBV DNA load, HBsAg, HBeAg, and alanine aminotransferase (ALT) level in patients with chronic HBV infection was analyzed. In total 312 subjects (184 males and 128 females) were enrolled in the study. There were significant differences among IT, CHB, and AHB groups in Flt-3L value (P = .003;H = 12.312), IFN-gamma (P = .001; H = 11.723), IL-10 (P = .001;H = 18.736), IL-17A ((P = .001;H = 12.735), and TGF-beta 1 (P = .001;Z = 48.571). IFN-alpha 2 levels in CHB group were significantly higher than those in IT and AHB groups (15.24 vs 35.78 pg/mL,P = .000;Z = 3.727; 13.88 vs 35.78 pg/mL,P = .024;Z = -2.258. In CHB group, the levels of HBsAg and ALT were positively correlated with the levels of IL-10 (r = .173;P = .006;r = 0.176;P = .006, respectively), while HBeAg level was positively correlated with the IFN-alpha 2 level (r = .153;P = .016). In AHB group, the HBsAg level was positively correlated with Flt-3L, IFN-alpha 2, IL-10, and IL-6 (r = .402;P = .023;r = .436;P = .016;r = .524,P = .002;r = .405;P = .022, respectively). HBeAg level was positively correlated with IFN-gamma and IL-17A levels (r = .400;P = .023;r = .373;P = .036, respectively), and ALT level was positively correlated with IL-6 levels (r = .367;P = .039). In either AHB or CHB group, HBV DNA load was only related to TGF-beta level (r = .493;P = .004;r = -.218,P = 0.009 respectively). The correlation between Flt-3L and HBsAg (F = 7.422;P = .007); IL-17, IL-6, and HBeAg (F = 5.757;P = .017;F = 6.156;P = .014) were statistically significant. There was significant correlation between TGF-beta 2 and HBV DNA (F = 11.795;P = .001), and between ALT and HBsAg, HBV DNA (F = 26.089;P = .000;F = 4.724;P = .031). HBsAg, HBeAg, and HBV DNA were correlated with cytokines and ALT in patients with HBV infection. The level of IFN-alpha 2 was significantly higher in patients with CHB. HBV DNA load was only correlated with the level of TGF-beta in acute or CHB.

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