Soluble immune markers in the different phases of chronic hepatitis B virus infection - PubMed (original) (raw)

doi: 10.1038/s41598-019-50729-5.

Bastian Beggel 3, Anika Wranke 1 2, Elmira Aliabadi 1 2, Jerzy Jaroszewicz 4, Cheng-Jian Xu 1 5, Yang Li 5 6, Michael P Manns 1, Thomas Lengauer 2 7, Heiner Wedemeyer 1 2 8, Anke R M Kraft 1 2, Christine S Falk 2 9, Markus Cornberg 10 11 12 13

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Soluble immune markers in the different phases of chronic hepatitis B virus infection

Steffen B Wiegand et al. Sci Rep. 2019.

Abstract

Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.

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Conflict of interest statement

J.J. has received compensation as a member of the scientific advisory board of Abbvie, Bristol-Myers Squib, Gilead Sciences, MSD Sharp & Dohme/Merck and Roche. He also hold lectures for Abbvie, Bristol-Myers Squib, Dia Sorin, Gilead Sciences, Grifols, MSD Sharp & Dohme/Merck, Roche, Woerwag and received lecture fees. M.P.M. has been funded by Roche, Bristol Myers Squibb, Gilead. He has received honoraria for consulting/holding lectures for Roche, Bristol Myers Squibb, Gilead, Medgenics, Enyo Pharma, Curevac. H.W. has received honoraria for consulting/speaking from BMS, Gilead, Janssen, Roche Diagnostics, Abbott, Roche. M.C.’s work has been funded by Roche Pharma. He has received compensation as a member of the scientific advisory board of Abbvie Deutschland GmbH, Bristol-Myers Squibb, Biogen Idec, Gilead Sciences, Janssen-Cilag, MSD Sharp & Dohme/Merck, Roche Diagnostics Roche Pharma. He also hold lectures for Falk Foundation e.V. and received lecture fees. S.B.W., C.F., E.A., A.R.M.K., B.B., A.W., C.J.X., Y.L. and T.L. declare no potential conflict of interest.

Figures

Figure 1

Figure 1

qHBsAg titers in chronic HBV. HBsAg titers in different phases of chronic HBV infection were quantified by using Abbott ARCHITECT assay (red: HBeAg positive, blue: HBeAg negative). Mann-Whitney U test was used for comparison of means.

Figure 2

Figure 2

SIM in phases of chronic HBV. (A) Significance evaluation of different virological, biochemical and immunological markers between phases of chronic HBV infection. The broken line indicates the significance threshold. Nonsignificant differences are marked with black dots. Significant differences are marked with a colored dot. Colored dots according to group color connotes significantly higher values of the parameter in this group compared to the other group. (B) Heat map showing the expression pattern of 14 soluble immune markers normalized by setting mean = 1 and variance = 0. The elements are colored according to the value of each SIM for each phase.

Figure 3

Figure 3

Correlation of SIM and ALT or HBV DNA. (A) Spearman rank correlation coefficients between SIM levels (rows) and ALT (left panel) or HBV DNA (right panel). Red indicates a significant positive correlation, whereas blue indicates a significant negative correlation. White color indicates non-significant (n.s.). (B) Spearman rank correlation between CXCL-10 and ALT in EPH (left) and ENH patients (right).

Figure 4

Figure 4

CXCL10, TGF-β2 and IL-17 titers in different phases of chronic HBV infection. (A) CXCL10 levels in HBeAg-positive and HBeAg-negative phases of chronic HBV infection (B) TGF-β2 and IL-17 levels in HBeAg-negative phases of chronic HBV infection. Mann-Whitney U test was used for comparison of means.

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