scholarly journals Genotype-Specific Genomic Markers Associated with Primary Hepatomas, Based on Complete Genomic Sequencing of Hepatitis B Virus

2008 ◽  
Vol 82 (7) ◽  
pp. 3604-3611 ◽  
Author(s):  
Joseph J. Y. Sung ◽  
Stephen K. W. Tsui ◽  
Chi-Hang Tse ◽  
Eddie Y. T. Ng ◽  
Kwong-Sak Leung ◽  
...  

ABSTRACT We aimed to identify genomic markers in hepatitis B virus (HBV) that are associated with hepatocellular carcinoma (HCC) development by comparing the complete genomic sequences of HBVs among patients with HCC and those without. One hundred patients with HBV-related HCC and 100 age-matched HBV-infected non-HCC patients (controls) were studied. HBV DNA from serum was directly sequenced to study the whole viral genome. Data mining and rule learning were employed to develop diagnostic algorithms. An independent cohort of 132 cases (43 HCC and 89 non-HCC) was used to validate the accuracy of these algorithms. Among the 100 cases of HCC, 37 had genotype B (all subgenotype Ba) and 63 had genotype C (16 subgenotype Ce and 47 subgenotype Cs) HBV infection. In the control group, 51 had genotype B and 49 had genotype C (10 subgenotype Ce and 39 subgenotype Cs) HBV infection. Genomic algorithms associated with HCC were derived based on genotype/subgenotype-specific mutations. In genotype B HBV, mutations C1165T, A1762T and G1764A, T2712C/A/G, and A/T2525C were associated with HCC. HCC-related mutations T31C, T53C, and A1499G were associated with HBV subgenotype Ce, and mutations G1613A, G1899A, T2170C/G, and T2441C were associated with HBV subgenotype Cs. Amino acid changes caused by these mutations were found in the X, envelope, and precore/core regions in association with HBV genotype B, Ce, and Cs, respectively. In conclusion, infections with different genotypes of HBV (B, Ce, and Cs) carry different genomic markers for HCC at different parts of the HBV genome. Different HBV genotypes may have different virologic mechanisms of hepatocarcinogenesis.

2017 ◽  
Vol 11 (09) ◽  
pp. 727-732 ◽  
Author(s):  
Liping Wang ◽  
Fangzheng Han ◽  
Hualing Duan ◽  
Fang Ji ◽  
Xuebing Yan ◽  
...  

Introduction: Previous studies have indicated that the drug-resistant mutations of hepatitis B virus (HBV) are a major obstacle to antiviral therapy. However, it is still unclear whether there are pre-existent resistance mutations in patients with HBV infection and the relationship between drug-resistant mutation, genotypes, and progression of hepatitis B disease. Methodology: A total of 357 treatment-naïve patients with HBV infection were involved in this retrospective study. The drug-resistant mutations of HBV reverse transcriptase domain were screened by direct gene sequencing. Results: Lamivudine (LAM) resistance was detected in 8 patients (3.7%) with chronic hepatitis B (CHB), 13 (11.7%) patients with liver cirrhosis (LC), and 6 (21.4%) patients with hepatocellular carcinoma (HCC). Adefovir(ADV)-resistant mutations were detected in 10 (4.6%) patients with CHB, 15 (13.5%) patients with  LC and 4 (14.5%) patients with HCC. Both LAM and ADV resistant mutations were detected in 2 patients (0.9%) with CHB, 1 patient (0.9%) with LC and 1 patient (3.6%) with HCC. Significant differences (p <0.01) were observed in the drug-resistance rates among patients with CHB, LC and HCC. Meanwhile, all the drug-resistant mutations were found in patients with HBV genotype C. Conclusions: This study demonstrated higher risk of pre-existing drug-resistant mutations in patients with HBV genotype C comparing to patients with HBV genotype B. Likewise, increasing prevalence of pre-existing drug-resistant mutations was shown, alongside with the progression of the disease.


2016 ◽  
Vol 10 (08) ◽  
pp. 837-844 ◽  
Author(s):  
Huijuan Zhu ◽  
Yiying Wang ◽  
Lugang Yu ◽  
Yunfang Xu ◽  
Hui Zhou ◽  
...  

Introduction: This study aimed to further analyze the associations between type 2 diabetes mellitus (T2DM) and hepatitis B virus (HBV) infection, and to investigate the relationships between T2DM and the mutations within the HBV major hydrophilic region (MHR). Methodology: In this cross-sectional study, 3,377 persons (338 T2DM patients and 3,039 non-diabetics) were randomly selected. HBsAg detection was performed by enzyme-linked immunosorbent assay. The HBV MHR was amplified, sequenced, and analyzed by nested PCR. Results: The seroprevalence of HBsAg was 21.30% in T2DM patients (72/338), which was significantly higher than in non-diabetics (15.53%). Compared to persons without T2DM, the proportion of T2DM patients positive for HBsAg was significantly elevated in males, people > 55 years (p = 0.039), and people with a body mass index (BMI) ≥ 24 kg/m2. Totally, 112 genotype B and 111 genotype C HBV sequences were isolated. No significant difference in HBV genotype distribution was observed between T2DM patients and non-diabetics. Compared to genotype C HBV-infected cases in non-diabetics, the amino acid substitution rates in the MHR were significantly higher in T2DM patients (p = 0.003). Moreover, seven HBV strains with stop codon mutations within the HBV S gene were identified: three from T2DM patients (5.45%) and four from non-diabetics (2.38%). Conclusions: In China, T2DM is significantly associated with chronic HBV infections and genotype C HBV MHR mutations. Being males, > 55 years of age, and ≥ 24 kg/m2 of BMI are the risk factors of HBV infection in T2DM patients.


2013 ◽  
Vol 35 ◽  
pp. 741-746 ◽  
Author(s):  
Bárbara B. Santana ◽  
Maria Luana C. Viégas ◽  
Simone R. S. S. Conde ◽  
Marluísa O. G. Ishak ◽  
Ricardo Ishak ◽  
...  

Objective. This study investigated the association of the single nucleotide polymorphisms (SNPs) in theFASandFASLgenes with the outcome of hepatitis B virus (HBV) infection.Methods. Blood samples were collected from 116 HBV-infected patients at the Hospital of the Santa Casa de Misericordia Foundation (Belém, PA, Brazil). Seronegative individuals were used as controls. DNA samples were extracted from the leukocytes and assayed using the polymerase chain reaction (PCR) followed by RFLP analysis with restriction endonucleases.Results. The frequencies of the mutant genotypes for -670FAS(GG), Ivs2nt-124FASL(GG), Ivs3nt-169FASL(ΔT/ΔT), and -844FASL(TT) were higher in the HBV patients, and theFAS-1377AA genotype was more frequent in the control group; however, the differences between the allele and genotype frequencies were not statistically significant. When the HBV patient population was divided into two groups (inactive carriers and active chronic hepatitis patients), the mutant genotypes were found to be more prevalent in the active chronic hepatitis group with respect to theFASgene polymorphisms; however, this difference was not statistically significant.Conclusions. The results suggest that the polymorphisms inFASandFASLgenes are not associated with HBV infection or even with the natural history of the infection in the Brazilian Amazon region.


2020 ◽  
Author(s):  
Eric Nyarko ◽  
Christian Obirikorang ◽  
W.K.B.A. Owiredu ◽  
Evans Adu Asamoah ◽  
Emmanuel Acheampong ◽  
...  

Abstract BackgroundSLC10A1 gene codes NTCP, a receptor through which the hepatitis B virus (HBV) gets access into hepatocytes - a stage of the viral cycle necessary for replication. Polymorphism variants of SLC10A1 play roles in HBV infection, viral clearance, treatment outcome, and complications, in diverse ethnic groups and countries. However, no such study has been conducted in the Ghanaian population, a country with HBV endemicity. Therefore, an exploratory study was conducted to investigate the presence of three (3) single nucleotide polymorphisms (SNPs) in the SLC10A1 gene (rs2296651, rs61745930, and rs4646287) and assessed the risk of HBV infection among the Ghanaian population.MethodPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the presence of the SNPs among 292 participants comprising 146 HBV infected persons as case-subjects and 146 HBV non-infected persons as control-subjects. ResultsThe minor allele frequency (T) of rs2296651 was present in a significantly high proportion of cases compared with the control group (12.6% vs. 3.1%, p < 0.0001). The homozygote recessive variant of rs61745930 was present in 2.7% of the control group and 5.5% of the case group. Moreover, the minor allele frequencies of rs4646287 were 9.6% and 8.6% among the control and the case group, respectively (p = 0.767). Under the dominant (CC) genetic model of inheritance, rs2296651 was found to be protective of HBV infection [OR = 0.18 (0.07–0.44)], whereas under the co-dominant and additive model, rs2296651 was a potential risk factor for HBV infection [OR = 5.2 (95%CI: 2.1–12.8); 3.5 (95%CI: 1.6–7.6], respectively. Variants of rs61745930 and rs4646287 were not associated with HBV infection (p > 0.05). Polymorphisms in SLC10A1, however, did not show any significant association with HBV infectivity (p > 0.05).ConclusionThe study highlights some polymorphism proof that variants rs2296651, rs61745930, and rs4646287 exist in HBV-infected individuals in Ghana. Variant rs2296651 was found to be associated with HBV infection. Nonetheless, polymorphisms in SLC10A1 were not associated with HBV infectivity among the Ghanaian population. Further investigation is warranted to assess the offensive role of the relationship between rs2296651 and HBV infectivity.


2012 ◽  
Vol 20 (2) ◽  
pp. 269-275 ◽  
Author(s):  
Qing-Qing Yao ◽  
Xiao-Lian Dong ◽  
Xue-Cai Wang ◽  
Sheng-Xiang Ge ◽  
An-Qun Hu ◽  
...  

ABSTRACTIt is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection (hnHBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1hnHBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1hnHBI/6) for those ofhnHBI mothers and 2.9% (1 HBsAg-positive HBV infection [hpHBI]/34) for those ofhpHBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have hadhnHBI. In comparison with thehpHBI cases, those withhnHBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the “a” determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission ofhnHBI can occur among those in the neonatal HBV vaccination program.


2004 ◽  
Vol 85 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Tran Thien-Tuan Huy ◽  
Hiroshi Ushijima ◽  
Vo Xuan Quang ◽  
Khin Maung Win ◽  
Pairoj Luengrojanakul ◽  
...  

A genomic characterization of hepatitis B virus (HBV) was done for 56 pre-S1/pre-S2 genes and 10 full-length HBV genotype C isolates from five Asian countries. Phylogenetic analysis of the pre-S1/pre-S2 genes revealed two major groups within genotype C: one for isolates from southeast Asia including Vietnam, Myanmar and Thailand (named HBV/C1) and the other for isolates from Far East Asia including Japan, Korea and China (named HBV/C2). This finding was confirmed by phylogenetic analysis based on the full-length sequence of 32 HBV genotype C isolates, including 22 from database entries. Two isolates from Okinawa, the island off the southern end of Japan, formed a different branch. Specific amino acid sequence changes were identified in the large S protein (amino acids 51, 54, 60, 62 and 73) and P protein (amino acids 231, 233, 236, 248, 252 and 304). Our results indicate that genotype C of HBV can be classified into at least two subgroups.


2018 ◽  
Vol 7 (3) ◽  
pp. 88-93
Author(s):  
Xuemei Li ◽  
Xiaoxia Li

Abstract Immune tolerance is a specific lack or negative response of T and B lymphocytes to antigen. According to different formation periods, immune tolerance can be divided into central and peripheral tolerances. The immune tolerance of the body to hepatitis B virus (HBV) after infection is the main cause of chronic HBV infection. In this paper, the functional defects of hepatitis B virus e antigen and dendritic cells, hyporesponsiveness of cytotoxic T lymphocyte, variation of helper T lymphocytes and cytokines, HBV genotype and genome, and the role of host gene polymorphism in the formation of immune tolerance in chronic HBV infection and its related research progress are introduced briefly.


2016 ◽  
Vol 10 (04) ◽  
pp. 427-431 ◽  
Author(s):  
Yiying Wang ◽  
Lugang Yu ◽  
Hui Zhou ◽  
Zhiwei Zhou ◽  
Huijuan Zhu ◽  
...  

Introduction: Previous studies have indicated that the patients with psychiatric illness were at higher risk of hepatitis B virus (HBV) infection. However, the efficacy of hepatitis B vaccine in schizophrenia patients remains unclear. Methodology: Between June 2014 and January 2015, 415 schizophrenia patients and 3,038 controls who had been routinely immunized as infants were recruited in the present study. Hepatitis B surface antigen (HBsAg), HBsAb, and HBV DNA were detected with commercial methods according to the manufacturer’s protocol. A 600-bp region of the S gene (region nt236–nt835) was amplified by nested polymerase chain reaction (PCR). The genotypes of isolated HBV were identified using phylogenetic analysis by the neighbor-joining algorithm in the software MEGA version 4.1. Results: The seroprevalence of HBsAg in schizophrenia patients was 6.75%, which was significantly higher than 3.32% measured in controls. HBsAg prevalence was 7.94% in male schizophrenia patients and 5.47% in female schizophrenia patients, while it was only 4.04% in males and 2.08% in females in the control group. The HBsAb seroprevalence rate was 58.31% in schizophrenia patients and 59.94% in non-schizophrenia controls. Moreover, one HBV strain in the schizophrenia group presented I126S vaccine escape mutation (5.88%), while three HBV isolates showed Q129H, M133L, and G145R vaccine escape mutations in the control group (6.81%). Conclusions: Schizophrenia patients are at higher risk for HBV infection, even those who had received routine immunization. Therefore, a booster HB vaccination targeted at schizophrenia patients should be considered in the future.


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