The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy
Open Access
- 25 January 2021
- journal article
- research article
- Published by Hindawi Limited in BioMed Research International
- Vol. 2021, 1-14
- https://doi.org/10.1155/2021/2178143
Abstract
Background. To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method. We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results. In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions. In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.Funding Information
- Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (2018ZX10715-005-003-005, D161100002716002, XMLX 201706, XXZ0302, 2017ZX10201201-001-006, 2017ZX10201201-002-006, XXT28, XMLX 202127, Z151100004015122)
This publication has 42 references indexed in Scilit:
- Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levelsHepatology, 2013
- Hepatitis B Surface Antigen Could Contribute to the Immunopathogenesis of Hepatitis B Virus InfectionISRN Gastroenterology, 2013
- NK cells: a double-edged sword in chronic hepatitis B virus infectionFrontiers in Immunology, 2012
- Natural Killer Cells Are Characterized by the Concomitantly Increased Interferon-γ and Cytotoxicity in Acute Resolved Hepatitis B PatientsPLOS ONE, 2012
- T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infectionWorld Journal of Gastroenterology, 2012
- Natural killer cells act as rheostats modulating antiviral T cellsNature, 2011
- Nucleoside/nucleotide analogues in the treatment of chronic hepatitis BJournal of Antimicrobial Chemotherapy, 2011
- Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patientsHepatology, 2010
- Early serum HBsAg drop: A strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patientsHepatology, 2008
- Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damageThe Journal of Experimental Medicine, 2007