Weihua Cao1,2, Minghui Li1,3, Lu Zhang1, Yao Lu1, Shuling Wu1, Ge Shen1, Min Chang1, Ruyu Liu1, Yuanjiao Gao1, Hongxiao Hao1, Leiping Hu1, Wei Yi4, Calvin Q Pan5,6, Yao Xie1,3. 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.
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.
Authors: Ming Hui Li; Lu Zhang; Xiao Jing Qu; Yao Lu; Gei Shen; Zhen Zhen Li; Shu Ling Wu; Ru Yu Liu; Min Chang; Lei Ping Hu; Wen Hao Hua; Shu Jing Song; Gang Wan; Yao Xie Journal: Biomed Environ Sci Date: 2017-03 Impact factor: 3.118
Authors: Claire Dunn; Maurizia Brunetto; Gary Reynolds; Theodoros Christophides; Patrick T Kennedy; Pietro Lampertico; Abhishek Das; A Ross Lopes; Persephone Borrow; Kevin Williams; Elizabeth Humphreys; Simon Afford; David H Adams; Antonio Bertoletti; Mala K Maini Journal: J Exp Med Date: 2007-03-12 Impact factor: 14.307