title: Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection.
abstract: BACKGROUND
  Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease.
  
  
  OBJECTIVE
  To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection.
  
  
  METHODS
  HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing.
  
  
  RESULTS
  Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either adefovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay.
  
  
  CONCLUSIONS
  The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus.
authors.affiliation: Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing, China. Electronic address: dtjykhua@126.com.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Hua
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.
authors.forename: Guanbin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease, Pingdingshan General Hospital Medical Group, Pingdingshan City, Henan Province, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.
authors.forename: Lanhua
authors.initials: L
authors.lastname: Sun
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing, China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Xiang
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D046228:Microarray Analysis; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage; D011379:Prognosis; D017422:Sequence Analysis, DNA; D000077712:Telbivudine; D013936:Thymidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000077712:Telbivudine; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine; D013936:Thymidine
keywords: Chronic HBV; Drug-resistance mutations; Genotyping; Microarray