Rivino L.Le Bert N.Gill U.S.Kunasegaran K.Cheng Y.Tan D.Z.M.Becht E.Hansi N.K.Foster G.R.TUNG-HUNG SUTAI-CHUNG TSENGLim S.G.JIA-HORNG KAONewell E.W.Kennedy P.T.F.Bertoletti A.2021-03-092021-03-0920180021-9738https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041452586&doi=10.1172%2fJCI92812&partnerID=40&md5=751c66fbbbbd35bd2d927eb9ff0d3d0ahttps://scholars.lib.ntu.edu.tw/handle/123456789/551083BACKGROUND. The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS. Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non–antigen-specific immune populations (NanoString and CyTOF). Two distinct cohorts of 19 and 27 chronic HBV patients, respectively, were analyzed longitudinally prior to and after discontinuation of 2 different NUC therapy strategies. RESULTS. Absence of hepatic flares following discontinuation of NUC treatment correlated with the presence, during NUC viral suppression, of HBV core and polymerase-specific T cells that were contained within the ex vivo PD-1+ population. CONCLUSIONS. This study identifies the presence of functional HBV-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1+ HBV–specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection.[SDGs]SDG3alanine aminotransferase; biological marker; hepatitis B surface antigen; hepatitis B(e) antigen; lamivudine; nucleoside analog; programmed death 1 receptor; tenofovir disoproxil; antivirus agent; biological marker; tenofovir; adult; alanine aminotransferase blood level; antiviral activity; antiviral therapy; Article; biochemical recurrence; CD4+ T lymphocyte; CD8+ T lymphocyte; chronic hepatitis B; clinical article; controlled study; disease association; drug potency; drug safety; drug withdrawal; enzyme linked immunospot assay; female; flow cytometry; Hepatitis B virus; human; male; medical history; monotherapy; natural killer cell; nonhuman; patient safety; peripheral blood mononuclear cell; priority journal; T lymphocyte; treatment withdrawal; viral clearance; virus core; virus replication; aged; blood; cell separation; chronic hepatitis B; cohort analysis; cytology; metabolism; middle aged; mononuclear cell; T lymphocyte; virology; Adult; Aged; Antiviral Agents; Biomarkers; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Separation; Cohort Studies; Female; Hepatitis B virus; Hepatitis B, Chronic; Humans; Lamivudine; Leukocytes, Mononuclear; Male; Middle Aged; T-Lymphocytes; Tenofovirjournal article10.1172/JCI92812293090502-s2.0-85041452586