Absence of hepatitis B virus precore mutants in patients with chronic hepatitis B responding to interferon‐α
Absence of hepatitis B virus precore mutants in patients with chronic hepatitis B responding to interferon‐α
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对干扰素-α 有反应的慢性乙型肝炎患者不存在乙型肝炎病毒前核心突变体
DOI：
10.1002/hep.1840150605
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发表时间：
1992
期刊：
影响因子：
13.5
通讯作者：
G. Dusheiko
中科院分区：
文献类型：
--
作者：
Jianye Xu;David Brown;T. Harrison;Yue Lin;G. Dusheiko
前C区缺陷的乙肝病毒变异株可能由于免疫选择而逐渐流行，并解释了乙肝病毒携带者从HBeAg到抗-HBe的自发血清转换。我们已经分析了前C区变异的存在是否是干扰素-α治疗应答的决定因素。对15名接受干扰素-α治疗的携带者(9名应答者和6名无应答者)进行了检查。治疗前、后分别采集血清标本。提取DNA后，用聚合酶链式反应扩增前核心区，经凝胶电泳、溴化乙锭染色、Southern印迹和分子杂交鉴定产物。所有患者的扩增产物通过改良的聚合酶链式反应进行不对称扩增，并对前核心区进行直接测序。所有患者最初均为HBVDNA阳性。在治疗前，无论是应答者还是无应答者，都没有发现循环中的HBeAg阴性突变。9名应答者治疗过程中或治疗后血清HBVDNA斑点杂交均为阴性，但7名应答者经聚合酶链式反应和Southern杂交检测仍为阳性。斑点印迹法检测所有无应答者的HBVDNA均为阳性。在7名携带者中发现了一种沉默突变，涉及第1888位的A替换G；然而，在干扰素-α应答者和无应答者的随访中都没有检测到HBeAg阴性突变。这些结果表明，在HBs Ag清除后的一段时间内，用聚合酶链式反应可以检测到HBVDNA。HBeAg阴性的乙肝病毒粒子的优势不能被认为是治疗反应的关键决定因素。前核心区的其他突变在决定治疗反应中的作用尚不确定。(《肝病》1992；15：1002-1006)。
Precore defective HBV mutants may gradually prevail because of immune selection and explain spontaneous seroconversion from HBeAg to anti‐HBe in HBV carriers. We have analyzed whether the presence of precore HBV mutants is a determinant of responsiveness to interferon‐α therapy. Fifteen carriers (nine responders and six nonresponders)who were treated with interferon‐α were examined. Serum samples were collected before and after therapy. After extraction of DNA, the precore region was amplified by the polymerase chain reaction, and the product was identified by gel electrophoresis and ethidium bromide staining and then Southern blotting and molecular hybridization. The amplified products in all patients were asymmetrically amplified by a modified polymerase chain reaction, and the precore region was directly sequenced. All patients were HBV DNA positive initially. Circulating HBeAg‐negative mutants were not identified before treatment in either responders or nonresponders. All nine responders were negative for HBV DNA in serum by dot blot during or after treatment, but seven remained positive by polymerase chain amplification and Southern‐blot hybridization. All of the nonresponders remained positive for HBV DNA by dot blot. A silent mutation involving the substitution of an A for G at position 1888 was found in seven carriers; however, no HBeAg‐negative mutants were detected in the follow‐up of either responders or nonresponders to interferon‐α. These results suggest that HBV DNA is detectable by polymerase chain reaction for a period after clearance of HBsAg. A predominance of HBeAg‐negative HBV virions cannot be considered a pivotal determinant of response to treatment. The role of other mutations in the precore region in determining response to therapy is uncertain. (HEPATOLOGY 1992;15:1002–1006).
DOI：
10.1073/pnas.83.6.1578
发表时间：
1986-03-01
影响因子：
11.1
作者：
OU, JH;LAUB, O;RUTTER, WJ
通讯作者：
RUTTER, WJ
影响因子：
3.7
作者：
P. Roingeard;J. Romet‐Lemonne;D. Leturcq;A. Goudeau;M. Essex
通讯作者：
P. Roingeard;J. Romet‐Lemonne;D. Leturcq;A. Goudeau;M. Essex