乙型肝炎病毒逆转录酶区N236T单独突变与N236T+A181T联合突变患者临床特征的比较

Patients with only N236T mutation and patients with N236T+A181T mutation in HBV reverse transcriptase region:a comparison of clinical characteristics

目的了解乙型肝炎病毒(HBV)逆转录酶区N236T单独突变患者与逆转录酶区N236T+A181T联合突变患者核苷(酸)类药物应用情况和病毒学特点的异同。方法对发生HBV逆转录酶区N236T单独突变与逆转录酶区N236T+A181T联合突变的慢性乙型肝炎患者的血清HBsAg、HBVDNA和丙氨酸转氨酶(ALT)水平进行检测和HBV基因分型,并对所有患者的核苷(酸)类药物治疗史进行回顾性调查。结果逆转录酶区N236T单独突变组与逆转录酶区N236T+A181T联合突变组相比较,两者血清HBsAg水平的差异无统计学意义(P=0.9755),但后者血清HBVDNA(P=0.0014)和ALT(P=0.0032)水平高于前者。此外,C型较B型容易发生rtN236T+rtA181T联合突变(40%vs20.45%,P=0.0235),由拉米夫定换用阿德福韦的治疗方式容易引起病毒突变。结论 HBV逆转录酶区N236T单独突变患者与逆转录酶区N236T+A181T联合突变患者在引起突变的核苷(酸)类药物的使用情况上存在一致性(拉米夫定换用阿德福韦),但基因型构成和血清病毒学指标存在明显差异。

Objective To compare the application of nucleotide drugs and the virology characteristics between patients with only N236T mutation and patients with N236T ＋ A181T mutation in the HBV reverse transcriptase（rt） region.Methods Sera of patients with only rtN236T mutation and patients with rtN236T ＋ rtA181T mutation were obtained from patients with chronic hepatitis B.Then the levels of sero-HBsAg,HBV DNA and ALT were determined and the HBV genotypes were analyzed.The treatment history with nucleotide drugs was retrospectively reviewed.Results The sero-HBsAg levels were not significantly different between only rtN236T mutation group and rtN236T ＋ rtA181T mutation group（P=0.975 5）,and significantly higher viral replication（P=0.001 4） and higher ALT level（P=0.003 2） were found in rtN236T ＋ rtA181T mutation group.Moreover,compared to HBV B genotype,patients with HBV C genotype were prone to carry rtN236T ＋ rtA181T mutation（40% vs 20.45%,P = 0.023 5） ;also we noticed that a switch from lamivudine medication to adefovir medication was liable to induce the virus mutation.Conclusion Nucleotide drug application in HBV patients with only rtN236T mutation and rtN236T ＋ rtA181T mutation are concurrent（lamivudine switching to adefovir）.However,the HBV genotype constituents and the serum virological characteristics are different between the two types of HBV patients.