Kim Jeong Han, Park Yong Kwang, Park Eun-Sook, Kim Kyun-Hwan
Jeong Han Kim, Digestive Disease Center, Department of Internal Medicine, School of Medicine, Konkuk University, Seoul 143-729, South Korea.
World J Gastroenterol. 2014 May 21;20(19):5708-20. doi: 10.3748/wjg.v20.i19.5708.
Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B (CHB). However, antiviral resistance remains an important challenge for long-term CHB therapy. All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase (RT), and all are reported to have resistant mutations. Since the hepatitis B virus (HBV) RT, like other viral polymerases, lacks proofreading activity, the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents. The molecular diagnosis of drug-resistant HBV is based on sequence variations, and current diagnostic methods include sequencing, restriction fragment polymorphism analysis, and hybridization. Here, we will discuss the currently available molecular diagnosis tools, in vitro phenotypic assays for validation of drug-resistant HBV, and treatment options for drug-resistant HBV.
在过去二十年中，已研发出用于治疗慢性乙型肝炎（CHB）的口服抗病毒药物。然而，抗病毒耐药性仍然是慢性乙型肝炎长期治疗的一项重大挑战。所有临床上可用的口服抗病毒药物都是针对病毒逆转录酶（RT）活性的核苷或核苷酸类似物，并且据报道都存在耐药突变。由于乙型肝炎病毒（HBV）逆转录酶与其他病毒聚合酶一样缺乏校对活性，在抗病毒药物给药产生的选择压力下，耐药性很容易出现。耐药性HBV的分子诊断基于序列变异，目前的诊断方法包括测序、限制性片段多态性分析和杂交。在此，我们将讨论目前可用的分子诊断工具、用于验证耐药性HBV的体外表型分析以及耐药性HBV的治疗选择。
