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

Author:

Cao Weihua12,Li Minghui13ORCID,Zhang Lu1ORCID,Lu Yao1ORCID,Wu Shuling1,Shen Ge1,Chang Min1,Liu Ruyu1,Gao Yuanjiao1,Hao Hongxiao1,Hu Leiping1,Yi Wei4ORCID,Pan Calvin Q.56ORCID,Xie Yao13ORCID

Affiliation:

1. Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang, Beijing 100015, China

2. Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing 101500, China

3. Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, No. 8 Jing Shun East Street, Chaoyang, Beijing 100015, China

4. Department of Obstetrics and Gynecology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Chaoyang District, Beijing 100015, China

5. Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

6. Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, New York University School of Medicine, New York, NY, USA

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.

Funder

Digestive Medical Coordinated Development Center of Beijing Hospitals Authority

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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