Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy
Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy
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DOI：
10.1053/jhep.2000.19618
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发表时间：
2000-11-01
期刊：
影响因子：
13.5
通讯作者：
Kim, JH
中科院分区：
文献类型：
--
作者：
Cho, SW;Hahm, KB;Kim, JH
拉米夫定给药对前核心/核心启动子突变进化的影响尚不清楚。本研究的目的是确定接受拉米夫定治疗的慢性乙型肝炎患者前核心/核心启动子序列的变化，从治疗前、治疗开始和治疗期间获得11名患者的连续血清。对血清样本进行聚合酶链反应扩增，并分析乙型肝炎病毒（HBV）的核苷酸序列。基线时，11 名患者中分别有 6 名和 4 名发现了前核心和核心启动子突变。在中位治疗 12 个月时，所有 6 名感染前核心突变体的患者的前核心终止密码子突变体均被野生型病毒取代（与治疗前相比；P = .011）。核心启动子突变仅出现在 10 名患者中的 1 名（相对于治疗前；P = .021），然而，在中位治疗 21 个月时，前核心和核心启动子突变分别出现在 10 名患者中的 5 名和 7 名。 2 名乙型肝炎 e 抗原 (HBeAg) 消失或血清转化的患者在拉米夫定停药后出现急性加重。在整个研究期间，血清保持 HBeAg 阴性，并且 2 名患者在急性加重期间均具有预核心野生型病毒。在 2 名基线时 HBV 基因组具有核心基因缺失的患者中，在长期治疗过程中，核心基因缺失的 HBV 突变体并未完全消除。总之，拉米夫定治疗导致前核心/核心启动子突变体回复为野生型。然而，在长期治疗过程中，前核心和核心启动子区域的突变再次出现。对于 HBeAg 消失或血清转化的患者，拉米夫定停药后可选择 HBeAg 阴性野生型预核心乙型肝炎病毒。
The effect of lamivudine administration on the evolution of precore/core promoter mutation is unknown. The aim of this study was to determine the changes of precore/core promoter sequences in chronic type B hepatitis patients treated with lamivudine, Serial sera were obtained from 11 patients before, at the beginning of, and during therapy. Serum samples were polymerase chain reaction-amplified, and nucleotide sequences of hepatitis B virus (HBV) were analyzed. At baseline, precore and core promoter mutations were found in 6 and 4 of 11 patients, respectively. A precore stop codon mutant was replaced by a wild-type virus in all 6 patients infected with precore mutant at a median treatment of 12 months (vs. before therapy; P = .011). Mutations in the core promoter appeared in only 1 of 10 patients (vs, before therapy; P = .021), However, precore and core promoter mutations appeared in 5 and 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had hepatitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeAg-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene deletions are not eliminated completely during prolonged therapy in 2 patients in whom the HBV genomes had core gene deletions at baseline. In conclusion, lamivudine therapy resulted in reversion from precore/core promoter mutants to wild-type. However, mutations in the precore and core promoter region reappeared during prolonged therapy. HBeAg-negative wild-type precore hepatitis B virus could be selected after lamivudine withdrawal in patients who had HBeAg loss or seroconversion.