title: Small surface antigen variants of HBV associated with responses to telbivudine treatment in chronic hepatitis B patients.
abstract: Nucleoside/nucleotide analogues are widely used to treat chronic HBV infection, but drug resistance is common. The role of HBV surface gene variants in drug resistance to nucleoside/nucleotide analogues is unknown. We are trying to investigate the dynamics of S gene mutations and how they relate to a patient's virological response in this study.
  
  
  
  Thirty patients with chronic hepatitis B were enrolled and serum samples were collected at multiple time points during treatment with telbivudine (LdT). The coding regions of the small surface antigen (S-HBsAg) were amplified and sequenced using the 454 GS FLX+System.
  
  
  
  Sequencing results revealed different dynamics of non-synonymous mutations, such as sL9P, sN40S, sG44E, sW172*, sW182* and sS187F, between patients with a complete virological response and those with a partial virological response. The viral population heterogeneity decreased at week 12 of LdT treatment in patients with a complete virological response, with a concomitant decline in non-synonymous mutations (from an average of 14 to 9.9 per sample) and an increase in the frequencies of major variants (from 14.3% to 40.4%).
  
  
  
  Our findings suggest that the decrease in viral population heterogeneity at an early stage of LdT treatment was associated with the subsequent optimal virological response, and the early appearance of some specific mutations, such as sG44E, sW172* and sW182*, is a potential indicator of a partial virological response in continuing therapy.
authors: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.
authors: Hui
authors: H
authors: Dong
authors: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Bin
authors: B
authors: Zhou
authors: School of Life Sciences, Fudan University, Shanghai, China.
authors: Hui
authors: H
authors: Kang
authors: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.|Shanghai Shenyou Biotechnology Co., Ltd, Shanghai, China.
authors: Weirong
authors: W
authors: Jin
authors: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.
authors: Yongqiang
authors: Y
authors: Zhu
authors: Shanghai Shenyou Biotechnology Co., Ltd, Shanghai, China.
authors: Yan
authors: Y
authors: Shen
authors: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Jian
authors: J
authors: Sun
authors: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.
authors: Shengyue
authors: S
authors: Wang
authors: Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China.|CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
authors: Guoping
authors: G
authors: Zhao
authors: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
authors: Jinlin
authors: J
authors: Hou
authors: CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Yungang
authors: Y
authors: He
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D009154:Mutation; D000072230:Sustained Virologic Response; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000077712:Telbivudine; D013936:Thymidine