TY - JOUR
T1 - A deep-sequencing method detects drug-resistant mutations in the hepatitis B Virus in Indonesians
AU - Widasari, Dewiyani Indah
AU - Yano, Yoshihiko
AU - Heriyanto, Didik Setyo
AU - Utsumi, Takako
AU - Yamani, Laura Navika
AU - Rinonce, Hanggoro Tri
AU - Wasityastuti, Widya
AU - Lusida, Maria Inge
AU - Soetjipto,
AU - Okada, Rina
AU - Murakami, Yoshiki
AU - Tanahashi, Toshihito
AU - Azuma, Takeshi
AU - Hayashi, Yoshitake
N1 - Publisher Copyright:
© 2014 S. Karger AG, Basel.
PY - 2014/12/17
Y1 - 2014/12/17
N2 - Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection.Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio).Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12- 1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%.Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.
AB - Objective: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection.Methods: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio).Results: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12- 1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%.Conclusion: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.
KW - Deep sequencing
KW - Hepatitis B virus
KW - Indonesia
KW - Nucleos(t)ide analogue
UR - http://www.scopus.com/inward/record.url?scp=84918841114&partnerID=8YFLogxK
U2 - 10.1159/000366420
DO - 10.1159/000366420
M3 - Article
C2 - 25382636
AN - SCOPUS:84918841114
SN - 0300-5526
VL - 57
SP - 384
EP - 392
JO - Intervirology
JF - Intervirology
IS - 6
ER -
