Mutations in preS genes of genotype C hepatitis B virus in patients with chronic hepatitis B and hepatocellular carcinoma

Zhi, Gao; Li, Tong; Jia, Weiping; Du, Ji Mei; Li, Ya Juan; Li, Jie; Lü, Feng; Zhang, Hui

doi:10.1007/s00535-007-2085-1

Cited by 53 publications

(46 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HBeAg expression and high viral load are associated with an increased risk of HCC (18,19). Some mutations in the PreS and the EnhII/BCP/Precore regions have been associated with the development of HCC (20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Our recent meta-analysis using published data up to August 31, 2008 has shown that HBV PreS mutations, C1653T, T1753V, and A1762T/G1764A, are associated with an increased risk of HCC (30).…”

Section: Introductionmentioning

confidence: 98%

“…In Mainland China, an endemic area with almost one third of the HBsAg carriers found worldwide (1), HBV genotypes and mutations have been investigated in a limited number of the hospital-based patients and selected geographic areas (21,22,24,25,27,31,32). However, no community-based epidemiologic study with sufficient participants has shown nationwide distribution of HBV genotypes and the prevalence of the HCC-associated viral mutations as well.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution and Hepatocellular Carcinoma–Related Viral Properties of Hepatitis B Virus Genotypes in Mainland China: A Community-Based Study

Yin

Zhang

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Introduction: Hepatitis B virus (HBV) genotypes, replication status, and mutations have been associated with the risk of hepatocellular carcinoma (HCC). Our aim was to study the distribution and HCC-related viral properties of HBV genotypes/subgenotypes in Mainland China.Methods: A multistage cluster probability sampling method was applied to select 81,775 participants between 1 and 59 years at 160 national disease surveillance points. We examined hepatitis B surface antigen, HBV genotypes and subgenotypes, hepatitis B e antigen, viral load, and mutations in the PreS and core promoter regions of HBV genome.Results: HBV subgenotypes B2 (27.3%), C1 (10.7%), and C2 (58.0%) were predominant. Genotype D (D1, 80.8%) was frequent in the Uygur. We identified a new subgenotype, C9, mainly in Tibetans. Compositions of subgenotypes B2 and C1 and genotype mixture increased from the North to Central South, which was consistently associated with the increasing prevalence of hepatitis B surface antigen. Hepatitis B e antigen positivity and viral loads were higher in the young with genotype B and declined more rapidly with increasing age than those with genotype C. In contrast to G1896A, PreS deletion, T31C, T1753V, and A1762T/ G1764A were more frequent in subgenotype C2 than in subgenotype B2. A1762T/G1764A, T1753V, C1653T, and G1896A, except PreS deletion, consecutively increased with increasing age.Conclusion: HBV subgenotypes B2, C1, and C2 are endemic in Mainland China. HBV genotype C exhibits less replication activity in the young and harbors higher frequencies of the HCC-associated mutations than genotype B.Impact: These basic data could help evaluate the association of HBV variations with HCC. Cancer Epidemiol

show abstract

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Distribution and Hepatocellular Carcinoma–Related Viral Properties of Hepatitis B Virus Genotypes in Mainland China: A Community-Based Study

Yin

Zhang

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…The HBV ENV ORF encodes three envelope proteins of graduating length: large (pre-S1, pre-S2, and S), middle (pre-S2 and S), and small/surface (S). The mRNAs of these envelope proteins are transcribed from a single ORF; however, each has its own initiation codon (11). In general, the number of pre-S mutations can increase during the progression of CHB (12), and pre-S mutations are more prevalent in patients with HCC and liver cirrhosis (13).…”

mentioning

confidence: 99%

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation

Betz‐Stablein

Töpfer

Yuen

et al. 2016

J Virol

View full text Add to dashboard Cite

Chronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV), replicates via an RNA intermediate and is error prone, leading to the rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome generated via splicing (spHBV variants). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. spHBV variants have been shown to enhance wildtype virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from samples, including the liver explant, longitudinally collected from a subject with CHB over a 15-year period after liver transplantation. By employing novel bioinformatics methods, this analysis showed that the dynamics of the viral population across a period of changing treatment regimens was complex. The spHBV variants detected in the liver explant remained present posttransplantation, and a highly diverse novel spHBV population as well as variants with multiple deletions in the pre-S genes emerged. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occurred with known drug resistance-associated mutations highlights the relevance of using full-genome deep sequencing and supports the hypothesis that drug resistance involves interactions across the full length of the HBV genome. IMPORTANCESingle-molecule sequencing allowed the characterization, in unprecedented detail, of the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimens. This analysis also showed the rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open-source bioinformatics tools with the capacity to easily identify potential spliced variants from deep sequencing data are freely available. H epatitis B virus (HBV) causes a widely prevalent chronic viral infection and infects 240 million people worldwide (1).Chronic hepatitis B (CHB) can lead to cirrhosis, liver failure, and hepatocellular carcinoma (HCC) (1, 2). HBV is a member of the Hepadnaviridae family and has a partially double-stranded relaxed circular DNA genome (3). The approximately 3,200-nucleotide (nt) genome consists of four overlapping, frame-shifted open reading frames (ORF) encoding the polymerase (P), envelope (ENV), X, and core (C) proteins. HBV can be divided into nine genotypes, labeled genotypes A to I, with a further putative genotype (genotype J) being proposed (4). With the exception of genotypes E and G, all genotypes can be further classified into subgenotypes. HBV genotypes differ in diversity by more than 8%,...

show abstract

“…The latest approach by using Mboll PCR restriction analysis also identified a novel mutation in pre-S2, it is reported that F141L mutation was significantly related to HCC, even in comparison to live cirrhosis among 241 Korean patients (Mun et al, 2011). As for pre-S deletion, it was (Gao et al, 2007) reported that these mutations were more commonly found in the patients with HCC that in the chronic hepatitis B or asymptomatic carrier, suggesting pre-S deletion might involved in HBV-related hepatocarinogenesis. Mutations in basal core promoter may also involved in the development of carcinoma, the result of direct sequencing revealed that mutations including A1896, A1899 and multiple mutations T1762/A1764+A1896, T1762/A1764+A1899, and T1762/A1764+A1896+A1899 were more common in cirrhotic hepatocellular carcinoma group and non-cirrhotic hepatocellular carcinoma than chronic hepatitis B patients (Zheng et al, 2011).…”

Section: Hbv Infectionmentioning

confidence: 98%

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

Su¹,

Yan²,

Cai³

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Mutations in preS genes of genotype C hepatitis B virus in patients with chronic hepatitis B and hepatocellular carcinoma

Abstract: PreS deletion mutations of genotype C HBV might play a role in HBV-related hepatocarcinogenesis.

Cited by 53 publications

References 47 publications

Distribution and Hepatocellular Carcinoma–Related Viral Properties of Hepatitis B Virus Genotypes in Mainland China: A Community-Based Study

Distribution and Hepatocellular Carcinoma–Related Viral Properties of Hepatitis B Virus Genotypes in Mainland China: A Community-Based Study

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

Contact Info

Product

Resources

About