Virological Breakthrough and Resistance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogues in Clinical Practice
Virological Breakthrough and Resistance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogues in Clinical Practice
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DOI：
10.1002/hep.24318
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发表时间：
2011-06-01
期刊：
影响因子：
13.5
通讯作者：
Lok, Anna S. F.
中科院分区：
文献类型：
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作者：
Hongthanakorn, Chanunta;Chotiyaputta, Watcharasak;Lok, Anna S. F.
病毒学突破（VBT）是慢性B肝炎（CHB）核苷（酸）类似物（NUC）治疗过程中抗病毒药物耐药的第一个表现，但并非所有VBT均由耐药引起。本研究旨在确定在临床实践中接受NUC的CHB患者中VBT和基因型耐药（GR）的发生率。对接受NUC的CHB患者的记录进行了审查。所有VBT患者均进行了耐药突变检测。在纳入的148例患者中，73%为男性，平均年龄为44.9岁。在平均37.5 ± 20.1个月的随访期间，39例（26%）患者至少接受了1次VBT。在这39例患者中，15例（38%）在复检时未证实有VBT，10例无GR证据。5年时VBT、证实的VBT和GR的累积概率分别为46.1%、29.7%和33.9%。在多变量分析中，未能检测到B型肝炎病毒（HBV）DNA是唯一与VBT显著相关的因素。在10名有VBT但没有确诊的VBT或GR并维持相同药物治疗的患者中，所有10名患者的血清HBV DNA均下降，9名患者在VBT后平均6.8个月时检测不到HBV DNA。4例患者持续检测不到HBV DNA，6例在随访期间HBV DNA一过性升高，无GR。结论：VBT是常见的慢性乙型肝炎患者接受NUCs在临床实践中，但近40%的VBT与抗病毒药物耐药无关。对CHB患者进行药物依从性咨询和VBT和/或GR的确认可以避免不必要的抗病毒药物变化。（肝脏学2011;53：1854-1863）
Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance. This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice. Records of patients with CHB who were receiving NUCs were reviewed. All patients with VBT were tested for drug resistance mutations. Of 148 patients included, 73% were men and mean age was 44.9 years. During a mean follow-up of 37.5 +/- 20.1 months, 39 (26%) patients had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%, respectively. In multivariate analysis, failure to achieve undetectable hepatitis B virus (HBV) DNA was the only factor significantly associated with VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were maintained on the same medications, serum HBV DNA decreased in all 10, and nine had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients had persistently undetectable HBV DNA, six had transient increase in HBV DNA during follow-up, and none had GR. Conclusion: VBT was common in patients with CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not related to antiviral drug resistance. Counseling of patients with CHB on medication adherence and confirmation of VBT and/or GR can avoid unnecessary changes in antiviral medications. (HEPATOLOGY 2011;53:1854-1863)