Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment |
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| Institution: | 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;1. Medical Faculty of Kunming University of Science and Technology, Kunming 650500, China;2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;1. First Hospital of Jilin University, Institute of Virology and AIDS Research, Changchun, Jilin Province, China;2. Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA;1. Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin;2. Department of Dermatology, University of Wisconsin Hospital and Clinics, Madison, Wisconsin;3. Radiation Oncology Associates Seacoast Cancer Center, Dover, New Hampshire;1. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia;2. Institute of Virology, University of Bonn Medical Centre, Bonn, Germany;1. Department of Pharmacy, University of Parma, Parma, Italy;2. Department of Health Science and Pediatrics, University of Torino, Torino, Italy;3. Department of Medical Sciences, University of Torino, Torino, Italy;4. Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy |
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| Abstract: | ObjectivesDeletion/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 methodsA 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.ResultsAmong 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.ConclusionDel/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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| Keywords: | Hepatitis B virus Deletion Insertion Whole genome HBeAg-positive Nucleos(t)ide analogue |
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