title: Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment.
abstract: OBJECTIVE
  Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment.
  
  
  METHODS
  A total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools.
  
  
  RESULTS
  Among 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion.
  
  
  CONCLUSIONS
  Del/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy.
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Hao
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Kuanhui
authors.initials: K
authors.lastname: Xiang
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Institute of Hepatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
authors.affiliation: Institute of Hepatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Mingze
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: zhuangbmu@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: tongli08@vip.sina.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D005260:Female; D016679:Genome, Viral; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D017422:Sequence Analysis, DNA; D000069078:Seroconversion; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens
keywords: Deletion; HBeAg-positive; Hepatitis B virus; Insertion; Nucleos(t)ide analogue; Whole genome