title: Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B.
abstract: OBJECTIVE
  To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
  
  
  METHODS
  Fifty-two hepatitis B envelope antigen (HBeAg) positive CHB patients were enrolled and divided equally into two groups. One group received telbivudine (LDT, 600 mg/d), and the other group received lamivudine (LAM, 100 mg/d). Clinical, virological and immunological parameters were assessed at the baseline and at 4, 12, 24, 36 and 48 wk.
  
  
  RESULTS
  Both groups achieved significant hepatitis B virus (HBV) replication inhibition and alanine aminotransferase normalization at 48 wk. At the baseline, compared to healthy controls, CHB patients had a lower circulating CD8 T cell frequency (29.44% ± 11.55% vs 37.17% ± 7.30%, P = 0.03) and higher frequencies of programmed death 1 positive CD8 T cells (PD-1+ CD8 T) (16.48% ± 10.82% vs 7.02% ± 3.62%, P = 0.0001) and CD4+ CD25+ FoxP3+ T regulatory cells (Tregs) (23.64% ± 9.38% vs 13.60% ± 6.06%, P = 0.001). On therapy, at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid (HBV DNA) and HBeAg declining, the frequencies of PD-1+ CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups. At treatment week 4, patients treated with LDT had a lower frequency of PD-1+ CD8 T cells compared to patients treated with LAM (10.08% ± 6.83% vs 20.51% ± 20.96%, P = 0.02). The frequency of PD-1+ CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level (r = 0.45, P = 0.01) and HBeAg level (r = 0.47, P = 0.01) at treatment week 24, but the frequency of Treg cells was only significantly correlated with the HBeAg level (r = 0.44,P = 0.02). Furthermore, the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.
  
  
  CONCLUSIONS
  NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines. This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Cheng-Zhong
authors: CZ
authors: Li
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Jing-Jing
authors: JJ
authors: Hu
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Jian-Ya
authors: JY
authors: Xue
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Wei
authors: W
authors: Yin
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Ya-Yun
authors: YY
authors: Liu
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Wen-Han
authors: WH
authors: Fan
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Hao
authors: H
authors: Xu
authors: Cheng-Zhong Li, Jian-Ya Xue, Wei Yin, Ya-Yun Liu, Wen-Han Fan, Hao Xu, Xue-Song Liang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Xue-Song
authors: XS
authors: Liang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002681:China; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D018836:Inflammation Mediators / Q000097:blood; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000821:virology; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016207:Cytokines; D004279:DNA, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006513:Hepatitis B e Antigens; D018836:Inflammation Mediators; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077712:Telbivudine; D019259:Lamivudine; D013936:Thymidine
keywords: CD4+ CD25+ FoxP3+ T regulatory cells; Chronic hepatitis B; Immune modulation; Nucleoside analogues; Programmed death-1