Hui Dong1, Bin Zhou2, Hui Kang3, Weirong Jin1,4, Yongqiang Zhu1, Yan Shen4, Jian Sun2, Shengyue Wang1, Guoping Zhao1,5,6, Jinlin Hou2,7, Yungang He8. 1. Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China. 2. State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. 3. School of Life Sciences, Fudan University, Shanghai, China. 4. Shanghai Shenyou Biotechnology Co., Ltd, Shanghai, China. 5. CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. 6. Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. 7. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China. 8. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Abstract
BACKGROUND: Nucleoside/nucleotide analogues are widely used to treat chronic HBV infection, but drug resistance is common. The role of HBV surface gene variants in drug resistance to nucleoside/nucleotide analogues is unknown. We are trying to investigate the dynamics of S gene mutations and how they relate to a patient's virological response in this study. METHODS: Thirty patients with chronic hepatitis B were enrolled and serum samples were collected at multiple time points during treatment with telbivudine (LdT). The coding regions of the small surface antigen (S-HBsAg) were amplified and sequenced using the 454 GS FLX+ System. RESULTS: Sequencing results revealed different dynamics of non-synonymous mutations, such as sL9P, sN40S, sG44E, sW172*, sW182* and sS187F, between patients with a complete virological response and those with a partial virological response. The viral population heterogeneity decreased at week 12 of LdT treatment in patients with a complete virological response, with a concomitant decline in non-synonymous mutations (from an average of 14 to 9.9 per sample) and an increase in the frequencies of major variants (from 14.3% to 40.4%). CONCLUSIONS: Our findings suggest that the decrease in viral population heterogeneity at an early stage of LdT treatment was associated with the subsequent optimal virological response, and the early appearance of some specific mutations, such as sG44E, sW172* and sW182*, is a potential indicator of a partial virological response in continuing therapy.
BACKGROUND:Nucleoside/nucleotide analogues are widely used to treat chronic HBV infection, but drug resistance is common. The role of HBV surface gene variants in drug resistance to nucleoside/nucleotide analogues is unknown. We are trying to investigate the dynamics of S gene mutations and how they relate to a patient's virological response in this study. METHODS: Thirty patients with chronic hepatitis B were enrolled and serum samples were collected at multiple time points during treatment with telbivudine (LdT). The coding regions of the small surface antigen (S-HBsAg) were amplified and sequenced using the 454 GS FLX+ System. RESULTS: Sequencing results revealed different dynamics of non-synonymous mutations, such as sL9P, sN40S, sG44E, sW172*, sW182* and sS187F, between patients with a complete virological response and those with a partial virological response. The viral population heterogeneity decreased at week 12 of LdT treatment in patients with a complete virological response, with a concomitant decline in non-synonymous mutations (from an average of 14 to 9.9 per sample) and an increase in the frequencies of major variants (from 14.3% to 40.4%). CONCLUSIONS: Our findings suggest that the decrease in viral population heterogeneity at an early stage of LdT treatment was associated with the subsequent optimal virological response, and the early appearance of some specific mutations, such as sG44E, sW172* and sW182*, is a potential indicator of a partial virological response in continuing therapy.