High rate of mutations in the hepatitis B core gene during the immune clearance phase of chronic hepatitis B virus infection
High rate of mutations in the hepatitis B core gene during the immune clearance phase of chronic hepatitis B virus infection
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DOI：
10.1002/hep.510240107
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发表时间：
1996-07-01
期刊：
影响因子：
13.5
通讯作者：
Lok, ASF
中科院分区：
文献类型：
--
作者：
Bozkaya, H;Ayola, B;Lok, ASF
横断面研究报告称，B型肝炎核心基因突变与活动性肝病和干扰素治疗反应性相关，鉴于已发表序列的异质性，不可能判断观察到的序列差异是否是感染过程中发生的真正突变，我们进行了一项纵向研究，以确定B型肝炎核心基因突变的发生率，以及这些突变与B型肝炎病毒复制、肝病活动、B e抗原（HBeAg）血清转换和干扰素治疗，通过直接测序B前C/C基因来分析来自55名慢性B感染患者的系列血清，以鉴定在随访期间出现的核苷酸和氨基酸变化，HBeAg阳性且转氨酶水平正常的患者（组I）维持较高的血清B型肝炎病毒（HBV）与HBeAg阳性但转氨酶水平升高的患者相比，（组II）和HBeAg清除的患者第I、II和III组患者的核苷酸和氨基酸变化率分别为：0.4 ± 0.1、1.9 ± 0.3和2.4 ± 0.4/核苷酸位置/年;和0.04 +/-0.02，0.21 +/-0.05，和0.38 +/-0.07/密码子/年。组II和组III患者中的大多数氨基酸变化发生在转氨酶水平Bares期间或之后不久，HBeAg血清转换之前。在干扰素治疗与未治疗的患者中发现相似的核苷酸和氨基酸变化率，应答者与无应答者之间，在HBeAg血清转换与无血清转换患者之间，干扰素治疗与未治疗患者之间，干扰素应答者与无应答者之间，B核心基因突变的位置或性质没有差异。总之，B型肝炎核心基因序列的改变在仍处于免疫耐受期的患者中很少被检测到，但在免疫耐受期的患者中，在慢性B型肝炎感染的免疫清除过程中发现了变化，干扰素治疗没有诱导更高的B型肝炎核心基因突变率或特异性模式。HBeAg阳性患者对干扰素治疗的反应与B型肝炎核心基因突变的数量或位置无关。
Cross-sectional studies reported that hepatitis B core gene mutations are associated with active liver disease and responsiveness to interferon therapy, In view of the heterogeneity in published sequences, it is not possible to tell whether the differences in sequences observed were true mutations that developed during the course of infection, We conducted a longitudinal study to determine the rate of hepatitis B core gene mutations and the timing of these mutations in relation to hepatitis B virus replication, activity of liver disease, hepatitis B e antigen (HBeAg) seroconversion, and interferon therapy, Serial sera from 55 patients with chronic hepatitis B infection were analyzed by direct sequencing of the hepatitis B precore/core gene to identify the nucleotide and amino acid changes that emerged during follow-up, Patients who remained HBeAg positive and had normal amino transferase levels (Group I) maintained higher serum hepatitis B virus (HBV) DNA levels but significantly lower rates of both nucleotide and amino acid changes during follow-up compared with patients who remained HBeAg positive but had elevated aminotransferase levels (Group II) and patients who cleared HBeAg (Group III), The rates of nucleotide and amino acid changes in Groups I, II, and III patients were: 0.4 +/- 0.1, 1.9 +/- 0.3, and 2.4 +/- 0.4/nucleotide position/year; and 0.04 +/- 0.02, 0.21 +/- 0.05, and 0.38 +/- 0.07/codon/year, respectively, Most of the amino acid changes in Groups II and III patients occurred during or shortly after Bares in aminotransferase levels, before HBeAg seroconversion, Similar rates of nucleotide and amino acid changes were found in interferon treated versus untreated patients, and in responders versus nonresponders, There was no difference in the location or nature of the hepatitis B core gene mutations between patients with and without HBeAg seroconversion, interferon treated versus untreated patients, and interferon responders versus nonresponders, In summary, changes in the hepatitis B core gene sequence were rarely detected in patients who were still in the immune tolerant phase but very high rates of changes were found during the immune clearance of chronic hepatitis B infection, Interferon therapy did not induce a higher rate or specific pattern of mutations in the hepatitis B core gene. Response to interferon therapy in HBeAg positive patients was unrelated to the number or location of hepatitis B core gene mutations.