title: Hepatitis B virus reverse transcriptase mutations in treatment Naïve chronic hepatitis B patients.
abstract: Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome lead to decreased susceptibility to nucleos(t)ide analogs approved for treatment of HBV infection. The aim of this study was to detect and analyze pre-existing HBV RT mutations in treatment naïve patients with chronic hepatitis B. Seventy one chronic HBV treatment naïve patients were enrolled from January 2009 to June 2011. HBV RT sequence analysis was done by using direct bidirectional sequencing of semi-nested PCR products. HBV genotypes were determined by multiplex PCR. Genotype D was found in 64 patients (90.1%) followed by genotype C and A which were present in 5 (7.0%) and 2 (2.8%) patients respectively. The results of the RT sequence analysis showed mutations in 34 (47.9%) patients. The rtH248N mutation was the most common mutation, accounting for 47.1% patients. Other common mutations included rtD263E/S, rtM129L, rtF122L/V/I, rtS135Y/H, rtQ149K, rtL91I, rtH126R, rtC256S/G, rtY257W, rtS259T and rtE271D, which were present in 26.5% (9/34), 29.4% (10/34), 20.6% (7/34), 20.6% (7/34), 20.6% (7/34), 17.6% (6/34), 14.7% (5/34), 14.7% (5/34), 11.8% (4/34), 11.8% (4/34) and 11.8% (4/34) patients respectively. The known primary drug resistance mutations were found in 3 (8.8%) patients. The present study shows the presence of RT amino acid substitutions in treatment-naïve patients with chronic hepatitis B, which may decrease susceptibility to available oral antiviral drugs. On the basis of the finding of this study, genotypic testing is recommended before the start of therapy in naïve patients, so that suitable antiviral drugs can be prescribed.
authors.affiliation: Departments of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Singla
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chakraborti
authors.forename: Bal Krishan
authors.initials: BK
authors.lastname: Sharma
authors.forename: Shweta
authors.initials: S
authors.lastname: Kapil
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Chawla
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Arora
authors.forename: Ashim
authors.initials: A
authors.lastname: Das
authors.forename: Radha K
authors.initials: RK
authors.lastname: Dhiman
authors.forename: Ajay
authors.initials: A
authors.lastname: Duseja
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D020125:Mutation, Missense; D015995:Prevalence; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012194:RNA-Directed DNA Polymerase
keywords: chronic hepatitis B; genotype; hepatitis B virus; nucleos(t)ide analogs; reverse transcriptase; semi-nested PCR