scholarly journals Distinct Hepatitis B Virus Dynamics in the Immunotolerant and Early Immunoclearance Phases

2010 ◽  
Vol 84 (7) ◽  
pp. 3454-3463 ◽  
Author(s):  
Hurng-Yi Wang ◽  
Ming-Hung Chien ◽  
Hsiang-Po Huang ◽  
Hsiao-Chi Chang ◽  
Chung-Che Wu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Early Stage ◽  
Host Immunity ◽  
Viral Population ◽  
Dominant Factor ◽  
Serum Samples ◽  
Copy Numbers ◽  
Viral Copy Number ◽  
B Virus

ABSTRACT Little is known about hepatitis B virus (HBV) diversity changes within a host during the immunotolerant phase of chronic HBV infection. Such knowledge, nevertheless, may help in understanding how host immunity and HBV interact at the early stage of infection. In this study, serial serum samples were collected from a long-term (>17 years) follow-up cohort of seven patients, and multiple copies of the full-length viral genome from serially sampled sera were recovered and analyzed. Viral genetic diversity was positively correlated with host immunity, represented by levels of alanine aminotransferase (ALT), but was negatively correlated with the viral copy number. During the immunotolerant phase, when the host immunity was feeble (ALT < 20 U/liter), viral nucleotide diversity decreased while copy numbers increased. Rates of evolutionary change derived for different patients were in a very narrow range (1.6 × 10−5 to 5.4 × 10−5/site/year). As the disease progressed toward the immunoclearance phase (ALT > 20 U/liter), viral diversity increased but copy numbers decreased. Evolutionary rates varied among patients in accordance with their levels of ALT, ranging from 9.6 × 10−6 to 3.2 × 10−4/site/year. More than half (19/32 sites) of positively selected sites resided in immune epitopes, suggesting their possible role in host immunity. Our results demonstrate that host immunity is a dominant factor in HBV evolution. Different selective forces, including immune-mediated positive selection and virus-mediated negative selection, operate in tandem in shaping viral population dynamics within a host.

scholarly journals Abundance of Noncircular Intrahepatic Hepatitis B Virus DNA May Reflect Frequent Integration Into Human DNA in Chronically Infected Patients

2020 ◽  
Author(s):  
Gustaf E Rydell ◽  
Simon B Larsson ◽  
Kasthuri Prakash ◽  
Maria Andersson ◽  
Heléne Norder ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Serum Levels ◽  
Digital Pcr ◽  
Hbv Dna ◽  
Serum Samples ◽  
Copy Numbers ◽  
B Virus ◽  
Liver Biopsies ◽  
Intrahepatic Hbv

Abstract Background Hepatitis B virus (HBV) integration has implications for cancer development and surface antigen (HBsAg) production, but methods to quantify integrations are lacking. The aim of this study was to develop a droplet digital PCR (ddPCR) assay discriminating between circular and integrated HBV DNA, and to relate the distribution between the two forms to other HBV markers. Methods ddPCR with primers spanning the typical linearization breakpoint in the HBV genome allowed for quantification of the absolute copy numbers of total and circular HBV DNA, and calculation of linear HBV DNA. Results Analysis of 70 liver biopsies from patients with chronic HBV infection revealed that the fraction of linear HBV DNA, which includes integrations, was higher in HBeAg-negative patients than HBeAg-positive. The ratio between HBsAg and HBV DNA levels in serum correlated with the intrahepatic proportion of linear HBV DNA. Furthermore, ddPCR experiments on serum samples and experiments with nuclease indicated the contribution of encapsidated double-stranded linear DNA and replication intermediates to be limited. Conclusions The degree of integration of intrahepatic HBV DNA in the HBeAg-negative stage may be higher than previously anticipated, and integrated DNA may explain the persistence of high HBsAg serum levels in patients with low HBV DNA levels.

scholarly journals Evaluation of Anti-HBs Antibody Immune Response against Hepatitis B virus in Vaccinated People in а North-eastern Bulgaria Region

Folia Medica ◽  
2019 ◽  
Vol 61 (4) ◽  
pp. 572-578
Author(s):  
Denitsa T. Tsaneva-Damyanova ◽  
Liliya I. Ivanova ◽  
Silviya N. Pavlova ◽  
Svetlana B. Todorova ◽  
Tsvetelina K. Popova
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Age Groups ◽  
University Hospital ◽  
Human Pathogens ◽  
Serum Samples ◽  
Post Vaccination ◽  
B Virus ◽  
Mass Immunization

Introduction: Hepatitis B virus (HBV) is one of the most significant human pathogens responsible for a huge number of acute and chronic liver infectious diseases worldwide. Aim: To find the duration of post-vaccination immune response in individuals allocated to five age groups from 6 months to 20 years. Materials and methods: All tested subjects were born between 1999 and 2018 and therefore covered by the compulsory vaccination program against hepatitis B. For the serological marker anti-HBs Ab we investigated 449 serum samples taken from ambulatory people and patients of St Marina University Hospital in Varna. Results: A positive antibody response (anti-HBs Ab > 10 mIU/ml) was reported in 79.7% (n = 51) of the group of subjects up to one year old, in 70.0% (n = 196) of the subjects in the age range 1 year/1 month to 15 years, and in 39.3% (n = 33) of the subjects 15 years/1 month to 20 years old. Female sex had a better post-vaccination response than male sex with statistically significant relationship between sex and anti-HBs Ab titer (&chi;2 = 24.76, p <0.01). Conclusions: Regardless of the mass immunization against HBV in Bulgaria, the relative share of chronic HBV infections does not show a downward trend. Therefore, it is very important to study the duration of the post-vaccination immune response by demonstrating the anti-HBs antibodies and to apply a booster dose from the vaccine if needed.

scholarly journals Whole-Exome Sequencing-Based Mutational Profiling of Hepatitis B Virus-Related Early-Stage Hepatocellular Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hao Zhan ◽  
Jiahao Jiang ◽  
Qiman Sun ◽  
Aiwu Ke ◽  
Jinwu Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Axon Guidance ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Stage ◽  
Genetic Characteristics ◽  
Whole Exome ◽  
B Virus

Background. Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortality in China with increasing incidence. This study is designed to explore early genetic changes implicated in HCC tumorigenesis and progression by whole-exome sequencing. Methods. We firstly sequenced the whole exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood samples, followed by gene ontological analysis and pathway analysis of the single-nucleotide variants discovered. Then, the mutations of high frequency were further confirmed by Sanger sequencing. Results. We identified a mutational signature of dominant T:A>A:T transversion in early HCC and significantly enriched pathways including ECM-receptor interaction, axon guidance, and focal adhesion and enriched biological processes containing cell adhesion, axon guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A, DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions. This study reveals a mutational profile and a distinct mutation signature of T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our understanding of genetic characteristics of the early-stage HCC.

scholarly journals Exome capture sequencing reveals new insights into hepatitis B virus-induced hepatocellular carcinoma at the early stage of tumorigenesis

2013 ◽  
Vol 30 (4) ◽  
pp. 1906-1912 ◽  
Author(s):  
YONG CHEN ◽  
LIJUAN WANG ◽  
HEXIANG XU ◽  
XINGXIANG LIU ◽  
YINGREN ZHAO
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Early Stage ◽  
Exome Capture ◽  
B Virus ◽  
Capture Sequencing

scholarly journals Sequence Variability of Hepatitis B Virus (HBV) Surface Antigen Gene (S Gene) Among the Non-responders of Antiviral Therapy

2021 ◽  
Author(s):  
Naveed Alam ◽  
Zubaida Daudzai
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Therapy ◽  
Chronic Hepatitis B ◽  
Surface Antigen ◽  
Sequence Variability ◽  
Serum Samples ◽  
S Gene ◽  
B Virus

Abstract BackgroundHepatitis B Virus (HBV), has been among the wide spread lethal causative agent of mortality in the population of Pakistan. Prolonged administration of antiviral therapy for chronic hepatitis B may result in the development of hepatitis B viral mutants. ObjectivesTo gain insight into the mechanism involved in the sequence variability of Hepatitis B Virus (HBV) surface antigen gene (S gene) among responders and non-responders to antiviral therapy, baseline characteristics of the patients and sequences within the S region were investigated in pre-treatment serum samples of responders and post-treatment serum samples of non-responders. Data collection and methodologyThe data was collected from 15 individuals with chronic hepatitis B from Khyber Pakhtunkhwa (KPK) province, Pakistan. The antiviral response was independent of viral genotypes, and nonresponse to antiviral therapy was associated with a complex variability of the viral mutants as determined by PCR. ResultsThe sequence analysis of the S gene among responders and non-responders patients of pre and post-treatment with antiviral therapy showed variability in DNA sequence marked as Pakistani isolates make a distinct cluster in the phylogenetic tree. The S gene of HBV isolates from KPK province shows some similarities with isolates of other countries. No significant variations of nucleotides in the S gene of HBV was found among the responders and non-responders receiving antiviral therapy indicating that S gene may not be important with respect to treatment outcome. ConclusionIt illustrates that antigenicity of other various HBV proteins can be targeted in order to design more effective vaccines against the local strains.

scholarly journals Evaluation of Hepatitis B Virus Nucleos(t)ide Analogues Resistance mutations in Treatment-Naïve Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Alireza Mohebbi ◽  
Hesamaddin Shirzad-Aski ◽  
Mohsen Ebrahimi
Keyword(s):  
Systematic Review ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Direct Sequencing ◽  
Meta Analysis ◽  
Viral Population ◽  
Current Therapy ◽  
P Value ◽  
B Virus ◽  
Treatment Naïve

Abstract Background: For detection of the nucleus(t)ide analog resistance (NAr) mutants among Hepatitis B virus (HBV) quasispecies, the selection of appropriate methodologies is necessary. Here, we aimed to investigate the role of different methods for the detection of NAr mutations among treatment-naïve patients with chronic HBV (CHB) infection.Methods: In this systematic review and meta-analysis study, five databases were searched. Desired data were extracted from the selected studies. The I2 was used as an indicator of heterogeneity. The NAr mutations rate was investigated with a 95% confidence interval (CI).Results: The overall ratio of occurrence of NAr within treatment-naïve CHB patients (14653) from 128 studies was 0.085 (95% CI, 0.069-0.103, p-value < 0.0001). Direct sequencing was the most prevalent method of DNA sequencing (56.25%). The rates of NAr mutations in the different methodologies, including the direct sequencing, InnoLipa, NGS, and PASS, were 0.079 (0.037-0.160, p < 0.0001), 0.058 (0.021-0.152, p < 0.0001), 0.729 (0.441-0.902, p = 0.114), and 0.448 (0.281-0.628, p = 0.001), respectively.Conclusions: Drug-resistant quasispecies of HBV exist in treatment-naïve patients in relatively high abundance. More sensitive methodologies like NGS should be used for detecting NAr fractions of the viral population. Replacement of current therapy with novel anti-HBV candidates also should be considered.

scholarly journals Comparison of the Characteristics of Hepatitis B Virus Whole Genomes Derived From Patients With Hepatocellular Carcinoma and Chronic Hepatitis B Infection

2020 ◽  
Author(s):  
Shuang Zhang ◽  
Feng Wang ◽  
He Liu ◽  
Qiudong Su ◽  
Feng Qiu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Public Health Problem ◽  
Full Length ◽  
Serum Samples ◽  
Hbv Genotypes ◽  
B Virus

Abstract Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection is a serious public health problem in China. The aims of the present study was to report HCC prevalence in China and characterize the whole gene sequences of HBV derived from patients diagnosed with HCC as well as those with chronic hepatitis B (CHB) infections.Methods: Patients in the HCC group and the CHB group were recruited from national HBV surveillance sites, which were matched by age, gender, and region. All serum samples were tested for serological markers. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then the analysis of the full-length HBV genomes was performed with bioinformatics and statistical software.Results: Serum samples were collected from 51 patients with HBV-related HCC and 76 patients with CHB. All patients were from six provinces (Guangxi, Hebei, Henan, Hunan, Qinghai, and Shanghai) in China. Sequencing and analysis of the full-length HBV genomes revealed the presence of four genotypes (B, C, CD, and I). The distribution of HBV genotypes and the positivity rate of the hepatitis B e antigen differed between the two groups. A total of 148 substitution sites deemed statistically significant were identified between the HCC and CHB groups. In addition, three mutational sites associated with HCC, (F22I/L/P in the pre-S2 region, P33S/T and S144A/T/V in the X region) were identified. Deletions to the pre-S and X regions were found in both HCC and CHB patients. However, deletions to the X region were more common in the HCC group than the CHB group.Conclusions: In this study the hotspot mutations associated with high risk of HCC mostly occurred in the sequences and some substitutions (C1470A/T, T1803A/G, and C1804T) that have not been previously reported. It was implicated that aa33 and aa144 substitution in X region may be new predictive markers for HCC. The results of our study would provide important basic information for HCC prevention.

scholarly journals Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to Hepatitis B virus infection

2020 ◽  
Author(s):  
CHAO LI ◽  
HANG LI ◽  
WEI SU ◽  
YU-BING WEN ◽  
WEI YE ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Renal Disease ◽  
Early Stage ◽  
Hbv Infection ◽  
Chinese Patients ◽  
Ultrastructural Studies ◽  
B Virus ◽  
Cryoglobulinemic Glomerulonephritis

Abstract BackgroundCryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. Methods This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed.Results Age at renal biopsy was 47±12 years, with female/male ration 3/4. Urine protein was 5.6(3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n=6), arthralgia (n=1), peripheral neuropathy (n=1), and cardiomyopathy (n=1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n=3), membranoproliferative Gn (n=3), and mesangial proliferative Gn (n=1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM(n=5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n=2) or combined with cyclophosphamide (n=4) or mycophenolate mofetil (n=1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8-5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %.ConclusionsThe etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early-stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

scholarly journals Seroprevalence of Hepatitis B Virus Infection amongst Pregnant Women in a Community North Central Nigeria

2021 ◽  
pp. 40-46
Author(s):  
Ndako, James A ◽  
Mawak, John D ◽  
Fajobi, Victor O ◽  
Ilochi Ifeanyi ◽  
Oludolapo Olatinsu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Pregnant Women ◽  
World Population ◽  
Hepatitis B Virus Infection ◽  
Serum Samples ◽  
B Virus ◽  
High Prevalence

Background: Hepatitis B virus (HBV) is a global challenge mostly in developing countries. Hepatitis B virus has infected almost one third of the world population. Pregnant women infected with hepatitis B virus (HBV) can transmit the infection to their fetuses and newborns. As a result of the developing status of most of our communities screening of antenatal attendees is rarely done as a routine in most health facilities that offers antenatal services, hence the need for this studies at our location of study. Methods: One hundred and ninety (190) serum samples were screened among pregnant women on ante-natal care, using standard ELISA method. A well-structured questionnaire was administered to individuals to determine incidence rates and identify relative risk factors that predispose subjects to the Hepatitis B Virus (HBV) infection. Results: From the total samples screened, Sixty-three, 63 (33.2%) were found to be positive for Hepatitis B virus. The highest prevalence was found among those aged 21-30 with overall number of 37(19.5%) Positivity, X2 =1.508; P=0.471. Considering educational status of subjects screened, high prevalence was recorded among those without formal education with 25(13.2%) Prevalence, x2= 5.381; P = 0.146 considering the various risk factors, subjects with history of tattooing/tribal markings recorded 41(21.6%), while women in their second trimester of pregnancy had a higher prevalence of 42(22.2%). Conclusions: This study recorded a high prevalence of Hepatitis B virus infection amongst pregnant women at our study location, which also reflects high probable risks of HBV perinatal transmission. It is therefore strongly recommended that pregnant women be routinely screened for Hepatitis B virus infection as part of antenatal care services.

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