阿德福韦酯治疗慢性乙型肝炎过程中发生病毒突破患者的（HBV）P基因变异分析

山东大学学报(医学版)

阿德福韦酯治疗慢性乙型肝炎过程中发生病毒突破患者的（HBV）P基因变异分析

刘峰，王磊，王丽娜，耿大影

山东大学医学院济南市传染病医院，济南 250021

收稿日期:2007-11-29 修回日期:1900-01-01 出版日期:2008-04-16 发布日期:2008-04-16
通讯作者: 王磊

P gene of hepatitis B virus in chronic hepatitis B patients who had viral-breakthrough during long-term adefovir dipivoxil monotherapy

LIU Feng, WANG Lei, WANG Li-na, GENG Da-ying

Jinan Infectious Disease Hospital, School of Medicine, Shandong Universtiy, Jinan 250021, China

Received:2007-11-29 Revised:1900-01-01 Online:2008-04-16 Published:2008-04-16
Contact: WANG Lei

摘要/Abstract

摘要： 目的观察阿德福韦酯（adefovir dipivoxil，ADV）单药治疗慢性乙型肝炎（慢乙肝）过程中发生病毒突破的患者乙型肝炎病毒（HBV）P基因区变异发生情况。方法选取51例阿德福韦酯单药治疗（10mg/d，疗程＞12月）发生病毒突破的慢乙肝患者作为研究对象，分别检测随访发现病毒突破时患者的血清ALT、HBV DNA水平，并采用PCR产物直接测序法分析HBV P区基因的变异发生情况。结果51例患者中有37例检测出阿德福韦酯耐药相关变异，且rt181位点变异多于rt236位点（分别为33例和8例，其中两位点联合变异4例，P＜0.001）。联合变异患者其血清HBV DNA水平高于单一变异患者［分别为（6.53±0.45）log10拷贝/mL、（5.37±1.08）log10拷贝/mL，P＝0.043］。结论在应用阿德福韦酯单药治疗的慢乙肝患者中可筛选出HBV P基因区的相关耐药变异，不同耐药位点患者的HBV DNA水平可有差异。

Abstract: To investigate the mutations in P gene of hepatitis B virus (HBV) in chronic hepatitis B(CHB) patients who had viral breakthrough during longterm adefovir dipivoxil monotherapy. Methods51 CHB patients who had viral breakthrough during longterm adefovir dipivoxil(ADV) monotherapy(10mg/d, duration >12 months) were enrolled in this study. Sera were collected when viral breakthrough was confirmed, and ALT, HBV DNA(real time quantitative PCR), and sequences of partial HBV P gene were determined. ResultsMutations related to ADV resistance were found in 37 of 51 CHB patients. The frequency of mutation at rt181 was significantly higher than that at rt236 (33 vs 8, P<0.001). Serum HBV DNA load in patients with combination mutation were higher than that with single mutation when the viral breakthrough occurred (6.53±0.45log10 copies/ml vs 5.37±1.08log10 copies/ml, P=0.043). ConclusionMutations in HBV P gene can be developed during ADV monotherapy in CHB patients. The HBV levels may differ in patients with different mutations.

Key words: Hepatitis B, chronic, Hepatitis virus B, Mutation, Adefovir dipivoxil, Drug resistance

中图分类号:

R512.6

刘峰,王磊,王丽娜,耿大影. 阿德福韦酯治疗慢性乙型肝炎过程中发生病毒突破患者的（HBV）P基因变异分析[J]. 山东大学学报(医学版), 2008, 46(4): 407-410.

LIU Feng,WANG Lei,WANG Li-na,GENG Da-ying. P gene of hepatitis B virus in chronic hepatitis B patients who had viral-breakthrough during long-term adefovir dipivoxil monotherapy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(4): 407-410.

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