Department of Clinical Virology, Christian Medical College, Vellore, 632 004, Tamil Nadu, India.
Mol Diagn Ther. 2014 Feb;18(1):63-71. doi: 10.1007/s40291-013-0054-3.
Management of chronic hepatitis B is a global public health challenge. There are several updated guidelines proposed based on treatment outcome data from the respective study populations. In this study, we aim to characterize the antiviral resistance mutations to lamivudine monotherapy in patients diagnosed with chronic hepatitis B from the Indian subcontinent.
A total of 147 lamivudine-treated patients with a median treatment duration of 13 (interquartile range 8-24) months were studied. Virological response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance mutations were identified by sequencing HBV reverse transcriptase domains. Factors associated with virological response and antiviral resistance mutations were analyzed.
Virological response was observed in 50 (35 %) patients while 84 (57 %) were non-responders. The virological response for the remaining 13 (9 %) patients was undetermined. Forty patients (27 %) developed lamivudine-resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen subtypes did not show significant association with virological response or lamivudine-resistant mutations. High HBV DNA levels and increased treatment duration were strongly associated with the development of lamivudine-resistant mutations (p = 0.002 and p < 0.001). Patients who continued to be positive for hepatitis B e antigen have an increased risk for treatment failure (p = 0.010). High baseline aspartate transaminase levels were significantly associated with subsequent lamivudine response (p = 0.037).
Considering the limited potency and high resistance rates to lamivudine therapy, our study emphasizes the use of more potent drugs in the management of chronic hepatitis B in the Indian subcontinent.
慢性乙型肝炎的管理是一个全球性的公共卫生挑战。有几项新的指南是基于各自研究人群的治疗结果数据提出的。在这项研究中，我们旨在描述来自印度次大陆的慢性乙型肝炎患者接受拉米夫定单药治疗后出现的抗病毒耐药突变情况。
共研究了 147 例接受拉米夫定治疗的患者，中位治疗时间为 13 个月（四分位间距 8-24）。通过乙型肝炎病毒（HBV）DNA 水平来衡量病毒学应答。通过测序 HBV 逆转录酶结构域来确定抗病毒耐药突变。分析与病毒学应答和抗病毒耐药突变相关的因素。
50 例（35%）患者观察到病毒学应答，84 例（57%）患者为无应答者。其余 13 例（9%）患者的病毒学应答情况无法确定。40 例（27%）患者发生拉米夫定耐药突变。HBV 基因型、亚型和乙型肝炎表面抗原亚型与病毒学应答或拉米夫定耐药突变均无显著相关性。高 HBV DNA 水平和治疗时间延长与拉米夫定耐药突变的发生密切相关（p=0.002 和 p<0.001）。持续乙型肝炎 e 抗原阳性的患者发生治疗失败的风险增加（p=0.010）。高基线天门冬氨酸氨基转移酶水平与后续拉米夫定应答显著相关（p=0.037）。
鉴于拉米夫定治疗的效力有限和耐药率较高，我们的研究强调在印度次大陆管理慢性乙型肝炎时应使用更有效的药物。
