Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection

• Published in: The Brazilian journal of infectious diseases 2015-05, Vol.19 (3), p.291-295
• Main Authors: Hua, Wenhao, Zhang, Guanbin, Guo, Shujun, Li, Weijie, Sun, Lanhua, Xiang, Guangxin
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Adenine - analogs & derivatives; Adult; Analysis; Antiviral Agents - administration & dosage; Asian Continental Ancestry Group; Care and treatment; Chronic HBV; DNA microarrays; DNA sequencing; DNA, Viral - genetics; Dosage and administration; Drug Resistance, Viral - genetics; Drug-resistance mutations; Female; Genotype; Genotyping; Guanine - administration & dosage; Guanine - analogs & derivatives; Health aspects; Hepatitis B; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Humans; INFECTIOUS DISEASES; Lamivudine; Lamivudine - administration & dosage; Male; Microarray; Microarray Analysis; Mutation; Nucleotide sequencing; Organophosphonates - administration & dosage; Original; Prognosis; Risk factors; Sequence Analysis, DNA; Thymidine - administration & dosage; Thymidine - analogs & derivatives
• ISSN: 1413-8670; 1678-4391; 1678-4391
• DOI: 10.1016/j.bjid.2015.03.012

Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. 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. 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. 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.