title: Pre-existing mutations in reverse transcriptase of hepatitis B virus in treatment-naive Chinese patients with chronic hepatitis B.
abstract: High rate of viral replication and lacking of proofreading activity in hepatitis B virus (HBV) polymerase lead to the generation of mutations in HBV virus. Mutations in the reverse transcriptase (RT) region of HBV polymerase are demonstrated to be strongly associated with drug resistance during antiviral treatment. However, the presence of mutations as well as its clinical significance in treatment-naïve hepatitis patients (defined as pre-existing mutations) need to be further investigated. In the present study, a total of 168 serum samples from treatment-naive chronic hepatitis B (CHB) patients were collected, and the RT region of HBV polymerase was sequenced. The results showed that pre-existing mutations in the RT region of HBV polymerase were detected in 43 of 168 (25.6%) treatment-naive CHB patients within which there were no well-characterized primary nucleotide analogs (NAs) resistance sites. Three dominant sites at rt191, rt207 and rt226 were found mutant in 7(16.28%), 8(18.60%), and 14(32.56%) samples respectively among these 43 patients. No significant correlation was found between pre-existing mutations and gender, age, HBV genotype, ALT, HBeAg or HBV DNA loads. However, patients with pre-existing RT mutations under HBeAg sero-negative status exhibited decreased HBV DNA loads, which contributed to the decreased HBV DNA loads in the total HBeAg sero-negative patients. The above investigation indicated that there was a prevalence of pre-existing mutations in RT region of HBV polymerase which might affect the serum HBV DNA level in treatment-naive CHB patients. Its effects on the occurrence of NAs resistance and the prognosis after treatment need to be further investigated.
authors.affiliation: Department of Infectious Diseases, No.3 People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai/Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, No.3 People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai/Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Deng-Yu
authors.initials: DY
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, No.3 People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai/Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai/Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012189:Retrospective Studies; D019562:Viral Load; D055815:Young Adult
chemical_list: D006513:Hepatitis B e Antigens; D012194:RNA-Directed DNA Polymerase
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