HBsAg mutations in patients with chronic hepatitis B undergoing adefovir dipivoxil resistance

doi:10.3877/cma.j.issn.1674-1358.2018.03.005

Abstract

Abstract:

Objective

To investigate adefovir dipivoxil (ADV) resistant mutation related HBsAg mutation, vaccine escape mutation and T cell epitope mutations in Chinese patients with chronic hepatitis B (CHB) who underwent adefovir resistance.

Methods

Seventy CHB patients who underwent ADV resistance from December 2007 to September 2011 in Beijing Ditan Hospital, Capital Medical Unversity were enrolled. While 70 ADV treated patients without ADV resistance were randomly selected as control group. HBV Rt/S ORF were sequenced with PCR product Sanger sequencing and pyrosequencing. ADV resistant mutation related HBsAg mutation, vaccine escape mutation and T cell epitope mutations were compared between ADV treated CHB patients with and without ADV resistance.

Results

Total of 70 ADV resistant patients with CHB were enrolled, while 70 ADV treated CHB patients without ADV resistance were set as control. Baseline characteristics were comparable between the two groups. All 42 rtA181T mutations were related to sW172^* mutations. Mean ratio of rtA181T/sW172^* mutations in quasispecies was (42.6 ± 22.1)% (12.2%-100%). More patients in resistance group showed vaccine escape mutation (χ² = 12.8736, P = 0.0003) and T cell epitope mutations (χ² = 4.8344, P = 0.0279) than control group.

Conclusions

In Chinese patients with CHB, rtA181T is mainly related to sW172^* mutations. ADV resistance is related to vaccine escape mutation and T cell epitope mutations. Further studies should focus on the possible mechanism.

Key words: Chronic hepatitis B, Hepatitis B virus, Adefovir dipivoxil, Hepatitis B surface antigen

Song Yang, Yue Li, Xiaomei Wang, Weini Ou, Huichun Xing, Jun Cheng. HBsAg mutations in patients with chronic hepatitis B undergoing adefovir dipivoxil resistance[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(03): 225-229.

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References 20

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相关指标		ADV耐药组（70例）	无ADV耐药组（70例）	统计量	P值
男性[例（%）]		56（80.0）	62（88.6）	χ² = 1.162	0.281
年龄（岁）
	平均年龄	35.8	35.5	t = 0.151	0.880
	年龄范围	27~70	18~67
ADV治疗时间（ ± s，月）		21.6 ± 11.6	19.2 ± 10.0	t = 1.246	0.215
HBV DNA（ ± s，log₁₀IU/ml）		4.9 ± 1.2	5.1 ± 1.2	t = 0.706	0.482
基因型[例（%）]
	B型	11（15.7）	16（22.9）
	C型	59（84.3）	54（77.1）	^χ2 = 1.147	0.284

相关指标		ADV耐药组（70例）	无ADV耐药组（70例）	统计量	P值
男性[例（%）]		56（80.0）	62（88.6）	χ² = 1.162	0.281
年龄（岁）
	平均年龄	35.8	35.5	t = 0.151	0.880
	年龄范围	27~70	18~67
ADV治疗时间（ ± s，月）		21.6 ± 11.6	19.2 ± 10.0	t = 1.246	0.215
HBV DNA（ ± s，log₁₀IU/ml）		4.9 ± 1.2	5.1 ± 1.2	t = 0.706	0.482
基因型[例（%）]
	B型	11（15.7）	16（22.9）
	C型	59（84.3）	54（77.1）	^χ2 = 1.147	0.284

耐药变异类型	耐药变异	合并HBsAg变异
rtA181T	28（40.0）	28（66.7）
rtA181V	12（17.1）	0（0.0）
rtN236T	7（10.0）	0（0.0）
rtA181T + rtA181V	1（1.4）	1（2.4）
rtA181T + rtN236T	11（15.7）	11（26.2）
rtA181V + rtN236T	9（12.9）	0（0.0）
rtA181T + rtA181V + rtN236T	2（2.9）	2（4.8）
合计	70（100.0）	42（100.0）

耐药变异类型	耐药变异	合并HBsAg变异
rtA181T	28（40.0）	28（66.7）
rtA181V	12（17.1）	0（0.0）
rtN236T	7（10.0）	0（0.0）
rtA181T + rtA181V	1（1.4）	1（2.4）
rtA181T + rtN236T	11（15.7）	11（26.2）
rtA181V + rtN236T	9（12.9）	0（0.0）
rtA181T + rtA181V + rtN236T	2（2.9）	2（4.8）
合计	70（100.0）	42（100.0）

疫苗逃逸变异类型	耐药组	无耐药组
sY100C	2（14.3）	0（0.0）
sS117T	1（7.1）	0（0.0）
sP120S	0（0.0）	1（25.0）
sI126V/S	1（7.1）	2（50.0）
sI126S + sT131N + s M133T + sD134E + sN139K	1（7.1）	0（0.0）
sI126V + sM133T + sD134S	1（7.1）	0（0.0）
sQ129R/H	1（7.1）	1（25.0）
sG130N	1（7.1）	0（0.0）
sT131N	1（7.1）	0（0.0）
sM133L/I	1（7.1）	0（0.0）
sG145A/R	4（28.6）	0（0.0）
合计	14（100.0）	4（100.0）

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