The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy

被引:21
作者
Cao, Weihua [1 ,2 ]
Li, Minghui [1 ,3 ]
Zhang, Lu [1 ]
Lu, Yao [1 ]
Wu, Shuling [1 ]
Shen, Ge [1 ]
Chang, Min [1 ]
Liu, Ruyu [1 ]
Gao, Yuanjiao [1 ]
Hao, Hongxiao [1 ]
Hu, Leiping [1 ]
Yi, Wei [4 ]
Pan, Calvin Q. [5 ,6 ]
Xie, Yao [1 ,3 ]
机构
[1] Capital Med Univ, Beijing Ditan Hosp, Dept Hepatol Div 2, 8 Jing Shun East St, Beijing 100015, Peoples R China
[2] Capital Med Univ, Miyun Teaching Hosp, Dept Infect Dis, Beijing 101500, Peoples R China
[3] Peking Univ, Dept Hepatol Div 2, Ditan Teaching Hosp, 8 Jing Shun East St, Beijing 100015, Peoples R China
[4] Capital Med Univ, Beijing Ditan Hosp, Dept Obstet & Gynecol, 8 Jing Shun East St, Beijing 100015, Peoples R China
[5] Capital Med Univ, Beijing Ditan Hosp, Ctr Liver Dis, Beijing 100015, Peoples R China
[6] NYU, NYU Langone Hlth, Dept Med, Div Gastroenterol & Hepatol,Sch Med, New York, NY 10016 USA
关键词
D O I
10.1155/2021/2178143
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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-) alpha-2a versus entecavir. The frequencies of NK, CD56(bright), CD56(dim), IFNAR2(+), NKp46(+), NKp46(bright), and NKp46(dim) 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-alpha-treated patients, posttreatment CD56(bright) NK cell frequency increased, but CD56(dim) NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56(bright) and CD56(dim) NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56(bright) NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-alpha responders from baseline, while changes were absent in PEG-IFN-alpha nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46(bright) and IFNAR2(+) NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions. In CHB patients, PEG-IFN-alpha 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. .
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页数:14
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共 42 条
[1]   Restored Function of HBV-Specific T Cells After Long-term Effective Therapy With Nucleos(t)ide Analogues [J].
Boni, Carolina ;
Laccabue, Diletta ;
Lampertico, Pietro ;
Giuberti, Tiziana ;
Vigano, Mauro ;
Schivazappa, Simona ;
Alfieri, Arianna ;
Pesci, Marco ;
Gaeta, Giovanni B. ;
Brancaccio, Giuseppina ;
Colombo, Massimo ;
Missale, Gabriele ;
Ferrari, Carlo .
GASTROENTEROLOGY, 2012, 143 (04) :963-+
[2]   Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion [J].
Costa, Juliana Bruder ;
Dufeu-Duchesne, Tania ;
Leroy, Vincent ;
Bertucci, Inga ;
Bouvier-Alias, Magali ;
Pouget, Noelle ;
Brevot-Lutton, Ophelie ;
Bourliere, Marc ;
Zoulim, Fabien ;
Plumas, Joel ;
Aspord, Caroline .
PLOS ONE, 2016, 11 (06)
[3]   Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage [J].
Dunn, Claire ;
Brunetto, Maurizia ;
Reynolds, Gary ;
Christophides, Theodoros ;
Kennedy, Patrick T. ;
Lampertico, Pietro ;
Das, Abhishek ;
Lopes, A. Ross ;
Borrow, Persephone ;
Williams, Kevin ;
Humphreys, Elizabeth ;
Afford, Simon ;
Adams, David H. ;
Bertoletti, Antonio ;
Maini, Mala K. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (03) :667-680
[4]   Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues [J].
Dusheiko, Geoffrey .
LIVER INTERNATIONAL, 2013, 33 :137-150
[5]   The Good and the Bad of Natural Killer Cells in Virus Control: Perspective for Anti-HBV Therapy [J].
Fisicaro, Paola ;
Rossi, Marzia ;
Vecchi, Andrea ;
Acerbi, Greta ;
Barili, Valeria ;
Laccabue, Diletta ;
Montali, Ilaria ;
Zecca, Alessandra ;
Penna, Amalia ;
Missale, Gabriele ;
Ferrari, Carlo ;
Boni, Carolina .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (20)
[6]   Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B [J].
Fung, James ;
Lai, Ching-Lung ;
Seto, Wai-Kay ;
Yuen, Man-Fung .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2011, 66 (12) :2715-2725
[7]   Transcriptome profiles of NK and T cells associated with immune control in chronic hepatitis B patients treated with pegylated interferon alpha-nucleos(t)ide analogue sequential therapy [J].
Gill, U. S. ;
Bert, N. L. ;
Kunasegaran, K. ;
Khakpoor, A. ;
Hansi, N. ;
Tan, D. ;
Rivino, L. ;
Singh, H. D. ;
Huang, W. -C. ;
Peppa, D. ;
Maini, M. K. ;
Bertoletti, A. ;
Kennedy, P. T. F. .
JOURNAL OF HEPATOLOGY, 2017, 66 (01) :S542-S542
[8]   Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo [J].
Gill, Upkar S. ;
Peppa, Dimitra ;
Micco, Lorenzo ;
Singh, Harsimran D. ;
Carey, Ivana ;
Foster, Graham R. ;
Maini, Mala K. ;
Kennedy, Patrick T. F. .
PLOS PATHOGENS, 2016, 12 (08)
[9]   Immune function of plasmacytoid dendritic cells, natural killer cells, and their crosstalk in HBV infection [J].
Golsaz-Shirazi, Forough ;
Amiri, Mohammad Mehdi ;
Shokri, Fazel .
REVIEWS IN MEDICAL VIROLOGY, 2018, 28 (06)
[10]   Immunobiology and pathogenesis of viral hepatitis [J].
Guidotti, Luca G. ;
Chisari, Francis V. .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2006, 1 (01) :23-61