Ran Hao1, Kuanhui Xiang1, Yaqin Peng1, Jinlin Hou2, Jian Sun2, Yao Li1, Mingze Su1, Ling Yan1, Hui Zhuang3, Tong Li4. 1. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. 2. Institute of Hepatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China. 3. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: zhuangbmu@126.com. 4. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address: tongli08@vip.sina.com.
Abstract
OBJECTIVES: Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment. MATERIALS AND METHODS: A total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools. RESULTS: Among 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion. CONCLUSION: Del/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy.
OBJECTIVES: Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment. MATERIALS AND METHODS: A total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools. RESULTS: Among 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion. CONCLUSION: Del/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy.
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