scholarly journals rt269I Type of Hepatitis B Virus (HBV) Polymerase versus rt269L Is More Prone to Mutations within HBV Genome in Chronic Patients Infected with Genotype C2: Evidence from Analysis of Full HBV Genotype C2 Genome

2021 ◽  
Vol 9 (3) ◽  
pp. 601
Author(s):  
Hyein Jeong ◽  
Dong Hyun Kim ◽  
Yu-Min Choi ◽  
HyeLim Choi ◽  
Donghyun Kim ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Statistical Significance ◽  
Hbv Dna ◽  
Type I ◽  
Chronic Patients ◽  
Hbv Genotype ◽  
Major Hydrophilic Region ◽  
B Virus

Recently, it has been reported that the rt269I type of hepatitis B virus (HBV) polymerase (Pol) versus the rt269L type is more significantly related to lower viral replication and HBeAg negative infections in chronic hepatitis B (CHB) patients of genotype C2. In this study, we compared mutation rates within HBV genomes between rt269L and rt269I using a total of 234 HBV genotype C2 full genome sequences randomly selected from the HBV database (115 of rt269L and 119 of rt269I type). When we applied the Benjamini and Hochberg procedure for multiple comparisons, two parameters, dN and d, at the amino acids level in the Pol region were significantly higher in the rt269I type than in the rt269L type. Although it could not reach statistical significance from the Benjamini and Hochberg procedure, nonsynonymous (NS) mutations in the major hydrophilic region (MHR) or “a” determinant in the surface antigens (HBsAg ORF) related to host immune escape or vaccine escape are more frequently generated in rt269I strains than in rt269L. We also found that there are a total of 19 signature single nucleotide polymorphisms (SNPs), of which 2 and 17 nonsynonymous mutation types were specific to rt269L and rt269I, respectively: Of these, most are HBeAg negative infections (preC-W28*, X-V5M and V131I), lowered HBV DNA or virion production (C-I97F/L, rtM204I/V) or preexisting nucleot(s)ide analog resistance (NAr) (rtN139K/H, rtM204I/V and rtI224V) or disease severity (preC-W28*, C-I97F/L, C-Q182K/*, preS2-F141L, S-L213I/S, V/L5M, T36P/S/A, V131I, rtN139K/H, rtM204I/V and rtI224V). In conclusion, our data showed that rt269I types versus rt269L types are more prone to overall genome mutations, particularly in the Pol region and in the MHR or “a” determinant in genotype C2 infections and are more prevalent in signature NS mutations related to lowered HBV DNA replication, HBsAg and HBeAg secretion and potential NAr variants and hepatocellular carcinoma (HCC), possibly via type I interferon (IFN-I)-mediated enhanced inflammation. Our data suggest that rt269L types could contribute to liver disease progression via the generation of immune escape or enhanced persistent infection in chronic patients of genotype C2.

N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape

2014 ◽  
Vol 60 (3) ◽  
pp. 515-522 ◽  
Author(s):  
De-Min Yu ◽  
Xin-Hua Li ◽  
Vannary Mom ◽  
Zhong-Hua Lu ◽  
Xiang-Wei Liao ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Major Hydrophilic Region ◽  
Virus Surface ◽  
B Virus ◽  
Hydrophilic Region

scholarly journals Prevalence of hepatitis B virus genotypes among patients with liver disease in Eritrea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammed Elfatih Hamida ◽  
Saud Mohammed Raja ◽  
Yodahi Petros ◽  
Munir Wahab ◽  
Yemane Seyoum ◽  
...  
Keyword(s):  
Viral Load ◽  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Genotype ◽  
Hbv Genotypes ◽  
B Virus ◽  
Intermediate Endemicity

AbstractEritrea is an East African multiethnic country with an intermediate endemicity for hepatitis B. Our aim was to establish the most prevalent genotypes of hepatitis B virus (HBV) among patients with liver disease. A total of 293 Eritrean patients with liver disease who were hepatitis B surface antigen (HBsAg) positive were enrolled. All sera were tested for liver transaminases, HBV DNA viral load, and hepatitis B seromarkers including HBsAg, anti-HBcAb (total), HBeAg, and anti-HBeAb. Those reactive for HBsAg and anti-HBc (total) were further tested for HBV genotyping. The median (interquartile range) of HBV DNA viral load and ALT levels were 3.47 (1.66) log IU/mL and 28 (15.3) IU/L, respectively. Using type-specific primer-based genotyping method, 122/293 (41.6%) could be genotyped. Irrespective of mode of occurrence, HBV genotype D (21.3%) was the predominant circulating genotype, followed by genotypes C (17.2%), E (15.6%), C/D (13.1%), and C/E (10.7%). Genotypes C/D/E (7.4%), A/D (4.9%), D/E (4.1%), A (2.5%), and B, A/E, B/E, and A/D/C (0.8%) were also present. HBV in Eritrea is comprised of a mixture of HBV genotypes. This is the first study of HBV genotyping among patients with liver disease in Eritrea.

scholarly journals Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region

2020 ◽  
Vol 11 ◽  
Author(s):  
Natalia M. Araujo ◽  
Sheila A. Teles ◽  
Natália Spitz
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Large Scale ◽  
Immune Escape ◽  
Diagnostic Procedures ◽  
Relevant Information ◽  
Geographic Region ◽  
Antiviral Resistance ◽  
Hbv Genotype ◽  
B Virus

Hepatitis B virus (HBV) is a highly variable DNA virus due to its unique life cycle, which involves an error-prone reverse transcriptase. The high substitution rate drives the evolution of HBV by generating genetic variants upon which selection operates. HBV mutants with clinical implications have been documented worldwide, indicating the potential for spreading and developing their own epidemiology. However, the prevalence of such mutants among the different HBV genotypes and subgenotypes has not been systematically analyzed. In the current study, we performed large-scale analysis of 6,479 full-length HBV genome sequences from genotypes A-H, with the aim of gaining comprehensive insights into the relationships of relevant mutations associated with immune escape, antiviral resistance and hepatocellular carcinoma (HCC) development with HBV (sub)genotypes and geographic regions. Immune escape mutations were detected in 10.7% of the sequences, the most common being I/T126S (1.8%), G145R (1.2%), M133T (1.2%), and Q129R (1.0%). HBV genotype B showed the highest rate of escape mutations (14.7%) while genotype H had no mutations (P < 0.001). HCC-associated mutations were detected in 33.7% of the sequences, with significantly higher frequency of C1653T, T1753V and A1762T/G1764A in genotype G than C (P < 0.001). The overall frequencies of lamivudine-, telbivudine-, adefovir-, and entecavir-resistant mutants were 7.3, 7.2, 0.5, and 0.2%, respectively, while only 0.05% showed reduced susceptibility to tenofovir. In particular, the highest frequency of lamivudine-resistant mutations was observed in genotype G and the lowest frequency in genotype E (32.5 and 0.3%; P < 0.001). The prevalence of HBV mutants was also biased by geographic location, with North America identified as one of the regions with the highest rates of immune escape, antiviral resistance, and HCC-associated mutants. The collective findings were discussed in light of natural selection and the known characteristics of HBV (sub)genotypes. Our data provide relevant information on the prevalence of clinically relevant HBV mutations, which may contribute to further improvement of diagnostic procedures, immunization programs, therapeutic protocols, and disease prognosis.

scholarly journals Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

1989 ◽  
Vol 31 (5) ◽  
pp. 328-335 ◽  
Author(s):  
João Renato Rebello Pinho ◽  
Luís Edmundo Pinto da Fonseca ◽  
Yu Song ◽  
Yuriko Miyamoto ◽  
Flair José Carrilho ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Dna Polymerase ◽  
Hbv Dna ◽  
Specific Marker ◽  
Chronic Patients ◽  
B Virus

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker of replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV - related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.

scholarly journals Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa

2007 ◽  
Vol 88 (10) ◽  
pp. 2686-2695 ◽  
Author(s):  
Daniel Candotti ◽  
Kwabena Danso ◽  
Jean-Pierre Allain
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cord Blood ◽  
Chronic Infection ◽  
Hbv Dna ◽  
Wild Type ◽  
Hbv Genotype ◽  
B Virus ◽  
Genotype E

To determine whether maternofetal transmission of hepatitis B virus (HBV) is a common route of infection leading to chronic infection in west Africa, plasma samples, obtained at delivery from 1368 pregnant Ghanaian women and paired umbilical cord blood or newborn whole blood samples, were tested for HBV surface antigen (HBsAg) and DNA. A 16 % prevalence of HBV chronic carriers, defined as detectable HBsAg and/or HBV DNA, was found, >80 % contained less than 1×104 IU ml−1 HBV DNA and 99 % were infected with genotype E strains. HBV maternofetal transmission was documented in 17 out of 204 (8.3 %) paired HBV carrier women–cord blood/newborn samples. The rate of transmission was 55 % and 3.3 % when maternal viral load was above or below 1×104 IU ml−1, respectively (P=0.0008). Maternofetal transmission of HBV genotype E was estimated to account for 8 % of the cases of chronic HBsAg carriers. Six women with low viral load at delivery (five <20 IU ml−1) and anti-HBe (hepatitis B e antigen) transmitted HBV. Surprisingly, while non-transmitted low viral load strains had 79 % mutations at position 1896 of HBV genome, transmitted strains were all wild-type despite anti-HBe presence (P=0.0041), suggesting the possible role of HBeAg as risk factor for HBV maternofetal transmission. The relative risk of maternofetal transmission was 2.4 when pregnant women carried high viral load and 11.5 when carrying wild-type strains at position 1896, irrespective of viral load. We conclude that viral load and pre-core wild-type at position 1896 are two independent risk factors for HBV genotype E maternofetal transmission, which remains a minor contributor to high prevalence of chronic infection.

scholarly journals Distribution of hepatitis B virus genotypes and viral load levels in Brazilian chronically infected patients in São Paulo city

2009 ◽  
Vol 51 (5) ◽  
pp. 269-272 ◽  
Author(s):  
Rosana Alcalde ◽  
Fernando Lucas Melo ◽  
Anna Nishiya ◽  
Suzete Cleusa Ferreira ◽  
Mario Dante Langhi Júnior ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Sao Paulo ◽  
Hbv Dna ◽  
São Paulo ◽  
Hbv Genotype ◽  
Direct Dna Sequencing ◽  
B Virus ◽  
Genotype A

The objective of the present study was to evaluate the serum viral load in chronically infected Hepatitis B virus (HBV) patients and to investigate the distribution of HBV genotypes in São Paulo city. Quantitative HBV-DNA assays and HBV genotyping have gained importance for predicting HBV disease progression, have been employed for assessing infectivity, for treatment monitoring and for detecting the emergence of drug resistance. Twenty-nine Brazilian patients with suspected chronic hepatitis B were studied, using real time PCR for viral load determination and direct DNA sequencing for the genotyping. The serology revealed chronic HBV infection in 22 samples. The HBV-DNA was positive in 68% samples (15/22). The phylogenetic analysis disclosed that eleven patients were infected with HBV genotype A, two with genotype F and two with genotype D. Thus, the genotype A was the most prevalent in our study.

scholarly journals Dendritic Cells in Uninfected Infants Born to Hepatitis B Virus-Positive Mothers

2010 ◽  
Vol 17 (7) ◽  
pp. 1079-1085 ◽  
Author(s):  
Lemonica J. Koumbi ◽  
Nikolaos G. Papadopoulos ◽  
Vassiliki Anastassiadou ◽  
Maria Machaira ◽  
Dimitris A. Kafetzis ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mononuclear Cells ◽  
Hbv Dna ◽  
Type I Interferons ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Dc System ◽  
B Virus

ABSTRACT Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-α) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-α production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-α production until the age of 6 months and inhibits IFN-α responses triggered by the TLR7 pathway.

High Viral Load and Hepatitis B Virus Subgenotype Ce Are Associated With Increased Risk of Hepatocellular Carcinoma

2008 ◽  
Vol 26 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Henry Lik-Yuen Chan ◽  
Chi-Hang Tse ◽  
Frankie Mo ◽  
Jane Koh ◽  
Vincent Wai-Sun Wong ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hazard Ratio ◽  
Hbv Genotype ◽  
Hbv Genotypes ◽  
B Virus ◽  
Genotype C

Purpose We aimed to investigate the impact of hepatitis B virus (HBV) DNA and HBV genotypes/subgenotypes on the risk of hepatocellular carcinoma (HCC). Patients and Methods A prospective cohort of patients infected with chronic HBV in a surveillance program for HCC since 1997 was studied. Ultrasound and alpha-fetoprotein evaluation were regularly performed to detect HCC. Risk factors for HCC and the relationship between HBV DNA and HBV genotypes were determined. Results Among 1,006 patients with a median follow-up of 7.7 years, 86 patients (8.5%) developed HCC. With reference to the low HBV DNA stratum (log HBV DNA ≤ 4.5 copies/mL), the hazard ratio for HCC of the intermediate HBV DNA stratum (log HBV DNA > 4.5 to 6.5 copies/mL) was 1.62 (95% CI, 1.05 to 2.48; P = .027) and that of the high HBV DNA stratum (log HBV DNA > 6.5 copies/mL) was 2.73 (95% CI, 1.76 to 4.25; P < .001). Among patients with genotyping results, 330 patients had HBV genotype B and 439 patients had HBV genotype C (94 subgenotype Ce and 345 subgenotype Cs). With reference to HBV genotype B, HBV subgenotype Ce has the highest risk of HCC (hazard ratio = 2.75; 95% CI, 1.66 to 4.56; P < .0001) and HBV subgenotype Cs has intermediate risk (hazard ratio = 1.70; 95% CI, 1.09 to 2.64; P = .020). On multivariate analysis, HBV DNA, HBV genotypes, liver cirrhosis, male sex, older age, and lower serum albumin were independent risk factors of HCC. Conclusion High HBV DNA level and HBV genotype C, particularly subgenotype Ce, increased the risk of HCC in chronic hepatitis B.

scholarly journals Genotypes of the hepatitis B virus within the area of Terni, Italy: our experience

2016 ◽  
Vol 31 (3) ◽  
Author(s):  
Michela Piermarini ◽  
Maria Chiara Medori ◽  
Alessandra Pagnani ◽  
Monica Proietti ◽  
Augusto Scaccetti
Keyword(s):  
Hepatitis B Virus ◽  
Nucleotide Sequence ◽  
Hepatitis B ◽  
Geographical Location ◽  
Hbv Dna ◽  
Native Population ◽  
Hbv Genotype ◽  
Hbv Genotypes ◽  
B Virus ◽  
The World

<em>Background and aims</em>: The presence of hepatitis B varies depending on the different areas of the world; 10 genotypes of hepatitis B virus (HBV) (A to J) have been identified, and they differ from one another in the nucleotide sequence and geographical location. The various genotypes are associated with a different evolution of the disease and with distinct responses to treatment. <br /><em>Materials and Methods:</em> From January 2010 to March 2014 we assessed the genotype of the HBV virus on 35 specimens with HBVDNA&gt;1000 IU/mL. The HBV genotype has been determined through sequencing. <br /><em>Results</em>: The 35 specimens belonged to individuals with a mean and median age of 42.8 and 40 years respectively: 17 of them were Italian and 18 from other countries. In total there were 19 males: 12 Italians and 7 foreigners. Females were 16: 5 Italians and 11 foreigners. The subjects with HBV-DNA≥10<sup>6</sup> IU/mL were prevailing, followed by subjects with HBV-DNA between 1000 IU/mL and 10.000 IU/mL. Out of 35 patients analysed by genotype, we found 20 genotypes D and 15 non-D genotypes. <br /><em>Conclusions</em>: The analyses carried out on results suggest that Italy, land of immigration, has become a multi-ethnic country with people coming from high and medium endemic disease areas in terms of HBV. Most patients show D genotype, however the migratory flows lead to the introduction of patients with non-D HBV genotypes in the native population as highlighted in Terni.

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