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Cytokine and chemokine signatures associated with hepatitis B surface antigen loss in hepatitis B patients
Sachiyo Yoshio, … , Junko Tanaka, Tatsuya Kanto
Sachiyo Yoshio, … , Junko Tanaka, Tatsuya Kanto
Published October 18, 2018
Citation Information: JCI Insight. 2018;3(20):e122268. https://doi.org/10.1172/jci.insight.122268.
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Clinical Medicine Hepatology Immunology

Cytokine and chemokine signatures associated with hepatitis B surface antigen loss in hepatitis B patients

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Abstract

BACKGROUND. The clearance of hepatitis B surface antigen (HBsAg) loss, defined as functional cure, is a clinical target in patients with chronic hepatitis B (CH). To understand the immune responses underlying functional cure, we evaluated cytokine and chemokine expression profiles from patients with resolving and nonresolving acute hepatitis B (AH). METHODS. We cross-sectionally evaluated 41 chemokines and cytokines at the peak of hepatitis in the sera from 41 self-limited AH patients who achieved HBsAg seroconversion, 8 AH patients who failed to clear HBsAg within 1 year after the diagnosis, 8 CH patients with hepatic flare, and 14 healthy volunteers. We longitudinally examined 41 chemokines and cytokines in the sera from 4 self-limited AH patients, 3 chimpanzees inoculated with hepatitis B virus (HBV), and 2 CH patients treated with nucleotide analogs and PEG–IFN-α, one resulting in functional cure. RESULTS. In AH patients and HBV-inoculated chimpanzees with HBsAg loss, CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 were elevated at hepatitis with subsequent decline of HBsAg. Interestingly, IL-21 elevation was observed only in resolving AH patients but not in nonresolvers. CXCL13 and IL-21 elevation was not observed in CH patients who failed to attain HBsAg loss, even at hepatic flare. A concomitant increase of CXCL13 and IL-21 was significant in CH patients who attained HBsAg seroconversion with a sequential therapy. CONCLUSION. Elevation of serum CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 might be a hallmark of functional cure of AH or CH patients.

Authors

Sachiyo Yoshio, Yohei Mano, Hiroyoshi Doi, Hirotaka Shoji, Tomonari Shimagaki, Yuzuru Sakamoto, Hironari Kawai, Michitaka Matsuda, Taizo Mori, Yosuke Osawa, Masaaki Korenaga, Masaya Sugiyama, Masashi Mizokami, Eiji Mita, Keiko Katayama, Junko Tanaka, Tatsuya Kanto

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Figure 1

The comparison of serum CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 levels for the patients with acute or chronic HBV infection.

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The comparison of serum CXCL9, CXCL10, CXCL11, CXCL13, and IL-21 levels ...
(A) Serum CXCL9, CXCL10, CXCL11, CXCL13, IL-21, ALT, HBV DNA, and HBsAg levels levels are shown. For patients with sAH, pAH, or CH at flare, samples obtained at the peak of alanine aminotransferase (ALT) elevation were analyzed. HV (n = 14), healthy volunteers; sAH (n = 41), self-limited acute hepatitis B patients; pAH (n = 8), acute hepatitis B patients who fail to clear HBsAg for more than 12 months after primary HBV infection; CH (n = 8), chronic hepatitis B patients; n.d., not detected; NT, not tested. Box-and-whisker plots show median, lower and upper quartiles, and minimum and maximum values. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by Kruskal-Wallis test. (B) Correlations between IL-21 and serum HBsAg, HBV DNA, and ALT levels at the peak of ALT elevation in AH patients (including the sAH and pAH groups). (C) Correlations between CXCL13 and serum HBsAg, HBV DNA, and ALT levels at the peak of ALT elevation in AH patients (including the sAH and pAH groups). (D) Correlations between serum CXCL9, CXCL10, CXCL11, and ALT levels at the peak of ALT elevation in AH patients (including the sAH and pAH groups). The values for Spearman’s correlation coefficient are given in B–D.

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