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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-?, 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.
SUBMITTER: Yoshio S
PROVIDER: S-EPMC6237466 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Yoshio Sachiyo S Mano Yohei Y Doi Hiroyoshi H Shoji Hirotaka H Shimagaki Tomonari T Sakamoto Yuzuru Y Kawai Hironari H Matsuda Michitaka M Mori Taizo T Osawa Yosuke Y Korenaga Masaaki M Sugiyama Masaya M Mizokami Masashi M Mita Eiji E Katayama Keiko K Tanaka Junko J Kanto Tatsuya T
JCI insight 20181018 20
<h4>Background</h4>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).<h4>Methods</h4>We cross-sectionally evaluated 41 chemokines and cytokines at the peak of hepatitis in the sera from 41 self-limited AH patien ...[more]