title: Higher prevalence of cancer related mutations 1762T/1764A and PreS deletions in hepatitis B virus (HBV) isolated from HBV/HIV co-infected compared to HBV-mono-infected Chinese adults.
abstract: In the era of combination therapy for human immunodeficiency virus (HIV), liver disease including hepatocellular carcinoma (HCC), are the major causes of death for patients co-infected with hepatitis B virus (HBV) and HIV. However, the mechanisms remain obscure. We aimed to determine whether HCC-related HBV mutations including 1762T/1764A double mutation and pre-S deletions occur more frequently in HBV/HIV co-infected individuals compared to HBV mono-infected individuals. In this study, the basic core promoter (BCP) and the preS/S regions of HBV isolated from 61 pairs of HBV/HIV co-infected and HBV mono-infected participants were analyzed. We found that the prevalence of HBV isolates with 1762T/1764A and/or preS deletion mutations was 37.7% (95% CI: 29.1-46.3). The prevalence of these mutations in HBV/HIV co-infected group (52.5%, 95% CI: 40.0-65.0) was significantly higher than in the HBV mono-infected group (23.0%, 95% CI: 12.4-33.6) (X2=11.307, P<0.05). HBV/HIV co-infection was associated with higher viral loads but these higher viral loads were not associated with the higher prevalence of HCC-related HBV mutations. Individually 1762T1764A (44.3%) or preS deletions (23%) occurred more frequently in isolates from co-infected compared to mono-infected individuals (21.3%, 4.9%, respectively) (X2=7.290, P<0.05; X2=8.270, P<0.05). Moreover, 1762T/1764A and preS deletions occurred more frequently in genotypes C and I compared to genotype B (p<0.05). Multivariate analysis revealed that co-infection with HIV was associated with the development of both 1762T/1764A ((RR: 2.932(1.325-6.488)) and preS deletions ((RR: 5.759(1.562-21.235)). These results demonstrate that co-infection with HIV was associated with increased prevalence of HCC-related mutations in HBV isolates from Chinese patients.
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Li
authors.affiliation: Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa.
authors.forename: Anna
authors.initials: A
authors.lastname: Kramvis
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China.
authors.forename: Shujia
authors.initials: S
authors.lastname: Liang
authors.affiliation: Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China.
authors.forename: Qin-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China.
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Yang
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Hu
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China; School of Preclinical Medicine, Guangxi Medical University, 22 ShuangYong Road, Nanning, Guangxi 530021, China.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Jia
authors.affiliation: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, 18 Jin Zhou Road, Nanning, Guangxi 530028, China. Electronic address: zhongliaofang@hotmail.com.
authors.forename: Zhong-Liao
authors.initials: ZL
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D018791:CD4 Lymphocyte Count; D002681:China / Q000453:epidemiology; D060085:Coinfection; D004279:DNA, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D015995:Prevalence; D017384:Sequence Deletion; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Co-infection; Genotype; Hepatitis B virus (HBV); Human immunodeficiency virus (HIV); Mutations; Prevalaence