TY - JOUR AU - Yoshio, Sachiyo AU - Mano, Yohei AU - Doi, Hiroyoshi AU - Shoji, Hirotaka AU - Shimagaki, Tomonari AU - Sakamoto, Yuzuru AU - Kawai, Hironari AU - Matsuda, Michitaka AU - Mori, Taizo AU - Osawa, Yosuke AU - Korenaga, Masaaki AU - Sugiyama, Masaya AU - Mizokami, Masashi AU - Mita, Eiji AU - Katayama, Keiko AU - Tanaka, Junko AU - Kanto, Tatsuya T1 - Cytokine and chemokine signatures associated with hepatitis B surface antigen loss in hepatitis B patients PY - 2018/10/18/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.122268 VL - 3 IS - 20 UR - https://doi.org/10.1172/jci.insight.122268 PB - The American Society for Clinical Investigation ER -