Departments of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
J Med Virol. 2013 Jul;85(7):1155-62. doi: 10.1002/jmv.23608.
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.
乙型肝炎病毒 (HBV) 基因组逆转录酶 (RT) 区的突变可导致对批准用于治疗 HBV 感染的核苷 (酸) 类似物的敏感性降低。本研究旨在检测和分析初治慢性乙型肝炎患者中存在的 HBV RT 突变。2009 年 1 月至 2011 年 6 月，共纳入 71 例初治慢性 HBV 患者。采用半巢式 PCR 产物的直接双向测序进行 HBV RT 序列分析。通过多重 PCR 确定 HBV 基因型。结果发现 64 例 (90.1%)患者为基因型 D，5 例 (7.0%)和 2 例 (2.8%)患者分别为基因型 C 和 A。RT 序列分析结果显示 34 例 (47.9%)患者存在突变。rtH248N 突变最为常见，占 47.1%患者。其他常见突变包括 rtD263E/S、rtM129L、rtF122L/V/I、rtS135Y/H、rtQ149K、rtL91I、rtH126R、rtC256S/G、rtY257W、rtS259T 和 rtE271D，分别占 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)和 11.8% (4/34)患者。发现 3 例 (8.8%)患者存在已知的原发性耐药突变。本研究表明，初治慢性乙型肝炎患者存在 RT 氨基酸取代，可能降低对现有口服抗病毒药物的敏感性。基于本研究的发现，建议在初治患者开始治疗前进行基因分型检测，以便开具合适的抗病毒药物。
