title: Comparison of Detection Rate and Mutational Pattern of Drug-Resistant Mutations Between a Large Cohort of Genotype B and Genotype C Hepatitis B Virus-Infected Patients in North China.
abstract: The study aimed to investigate the association of prevalent genotypes in China (HBV/C and HBV/B) with HBV drug-resistant mutations. A total of 13,847 nucleos(t)ide analogue (NA)-treated patients with chronic HBV infection from North China were enrolled. HBV genotypes and resistant mutations were determined by direct sequencing and confirmed by clonal sequencing if necessary. HBV/B, HBV/C, and HBV/D occupied 14.3%, 84.9%, and 0.8% across the study population, respectively. NA usage had no significant difference between HBV/B- and HBV/C-infected patients. Lamivudine-resistant mutations were more frequently detected in HBV/C-infected patients, compared with HBV/B-infected patients (31.67% vs. 25.26%, p < 0.01). Adefovir- and entecavir-resistant mutation detection rates were similar, but the mutational pattern was different between the two genotypes. For adefovir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtA181 V (HBV/C 5.29% vs. HBV/B 1.36%, p < 0.01) and a lower detection rate of rtN236T (2.70% vs. 6.54%, p < 0.01). For entecavir-resistant mutations, HBV/C-infected patients had a higher detection rate of rtM204 V/I+T184 substitution or S202G/C (3.66% vs. 2.16%, p < 0.01) and a lower detection rate of rtM204 V/I+M250 V/I/L substitution (0.67% vs. 1.46%, p < 0.01). Multidrug-resistant mutations (defined as coexistence of mutation to nucleoside and nucleotide analogues) were detected in 104 patients. HBV/C-infected patients had a higher detection rate of multidrug-resistant mutation than HBV/B-infected patients (0.83% vs. 0.35%, p < 0.05). The study for the first time clarified that HBV/C-infected patients had a higher risk to develop multidrug-resistant mutations, compared with HBV/B-infected patients; and HBV/C- and HBV/B-infected patients had different inclinations in the ETV-resistant mutational pattern.
authors: 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China .
authors: Xiaodong
authors: X
authors: Li
authors: 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China .
authors: Yan
authors: Y
authors: Liu
authors: 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China .
authors: Shaojie
authors: S
authors: Xin
authors: 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China .
authors: Dong
authors: D
authors: Ji
authors: 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China .
authors: Shaoli
authors: S
authors: You
authors: 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China .
authors: Jinhua
authors: J
authors: Hu
authors: 2 Medical Center for Liver Failure , Beijing 302 Hospital, Beijing, China .
authors: Jun
authors: J
authors: Zhao
authors: 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China .
authors: Jingjing
authors: J
authors: Wu
authors: 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China .
authors: Hao
authors: H
authors: Liao
authors: 3 Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University , Shanghai, China .
authors: Xin-Xin
authors: XX
authors: Zhang
authors: 1 Research Center for Clinical and Translational Medicine , Beijing 302 Hospital, Beijing, China .
authors: Dongping
authors: D
authors: Xu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002681:China; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D059645:Mutation Rate; D063065:Organophosphonates / Q000627:therapeutic use; D010802:Phylogeny; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D014764:Viral Proteins; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine
keywords: drug resistance; genotype; hepatitis B virus