乙型肝炎病毒（hepatitis B virus, HBV）感染是一项全球性公共卫生问题，其是引起慢性肝炎、肝硬化、肝细胞癌的主要致病因素。目前，治疗HBV 感染的药物主要分为两类：干扰素（interferon，IFN）和核苷/核苷酸类似物（nucleic acid，NA），其中后者通过作用于病毒基因活性区发挥抑制病毒增殖的功能，但在该类药物治疗中易致HBV 基因组突变，从而使HBV 产生耐药性，最终降低疗效，甚至无治疗效果。尽管目前对HBV 感染的治疗取得了一定进展，然而，如何能持久地抑制病毒复制，始终是临床面临的主要挑战。因此，对耐药突变进行早期、快速检测具有重要临床意义，这样可降低肝脏相关疾病发生和患者死亡风险，使慢性HBV 感染的监测达到最优化。理想的HBV 耐药突变检测方法需具备灵敏度和准确度高、重复性好、易操作、高通量、能够检测出混合新突变株的特点。现将HBV 耐药突变检测方法研究和临床应用进展阐述如下。

Hepatitis B virus (HBV) infection is a global public health problem, which causes chronic hepatitis B, cirrhosis and hepatocellular carcinoma. At present, antiviral drugs for HBV can be classified into two types: interferon and nucleoside analogues; the later plays a role in suppressing viral replication by acting on the virus gene activity area, but it easily causes drug resistance mutations in HBV polymerase gene and eventually leads to treatment failure. Despite the progress in HBV treatment, how to achieve durable viral suppression has always remains a major clinical challenge. Therefore, early and rapid detection methods are important for finding drug-resistance mutations, so as to reduce the risk of liver-related morbidity and mortality, thus optimize the management of Chronic HBV infection.