Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir.
Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir.
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DOI：
10.2147/dddt.s65349
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kumada H
中科院分区：
文献类型：
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作者：
Suzuki F;Sezaki H;Akuta N;Suzuki Y;Kawamura Y;Hosaka T;Kobayashi M;Saitoh S;Arase Y;Ikeda K;Kobayashi M;Watahiki S;Mineta R;Suzuki Y;Kumada H
富马酸替诺福韦酯（TDF）在美国和欧洲广泛用于治疗B型肝炎病毒（HBV）患者。尚未报告TDF治疗初治和核苷/核苷酸类似物治疗的慢性B型肝炎患者期间的耐药选择。在此，我们首次报道了一例慢性B型肝炎和肝硬化患者，在TDF和恩替卡韦（ETV）联合治疗中出现病毒学突破，对抗ETV耐药病毒。一名51岁的日本女性，携带B e抗原（HBeAg），基因型为C，由于HBV DNA水平>3.5 log拷贝/mL，连续接受ETV单药治疗，随后接受TDF和ETV联合治疗。在联合治疗开始时，检测逆转录酶（rt）基因rtL 180 M、rtT 184 I/M和rtM 204 V的氨基酸取代。在此之后，血清HBV DNA下降到低于2.1 log拷贝/mL，并保持在该水平，直到联合治疗31个月，当它再次开始增加。rtL 180 M、rtS 202 G和rtM 204 V的氨基酸替换出现，并与病毒学突破时血清HBV DNA的增加相关。长期使用TDF治疗ETV耐药病毒有可能诱导病毒学突破和耐药性，应进行仔细的随访。
Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out.