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.

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.

• Authors: Ran Hao, Kuanhui Xiang, Yaqin Peng, Jinlin Hou, Jian Sun, Yao Li, Mingze Su, Ling Yan, Hui Zhuang, Tong Li
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 33 Pg. 261-8 (Jul 2015) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 25976382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Biomarkers
• Hepatitis B Surface Antigens
• Hepatitis B e Antigens

Topics

• Adolescent
• Adult
• Antiviral Agents (therapeutic use)
• Biomarkers
• Female
• Genome, Viral
• Hepatitis B Surface Antigens (blood)
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (genetics)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Humans
• INDEL Mutation
• Male
• Sequence Analysis, DNA
• Seroconversion
• Treatment Outcome
• Viral Load
• Young Adult