scholarly journals 3D landscape of Hepatitis B virus interactions with human chromatins

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Bo Yang ◽  
Boyuan Li ◽  
Liyang Jia ◽  
Yongpeng Jiang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Spatial Organization ◽  
Active Regions ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Cellular Models ◽  
Hbv Cccdna ◽  
Genome Wide ◽  
Highly Sensitive ◽  
Virus Interactions

AbstractHepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromatin. Here we employed a highly sensitive technology, 3C-high-throughput genome-wide translocation sequencing (3C-HTGTS), to globally identify HBV DNA–host DNA contacts in cellular models of HBV infection. HBV DNA does not randomly position in host genome but instead preferentially establishes contacts with the host DNA at active chromatin regions. HBV DNA–host DNA contacts are significantly enriched at H3K4me1-marked regions modified by KMT2C/D; this histone modification is also observed in the HBV cccDNA mini-chromosome and strongly influences HBV transcription. On the other hand, chromatin loop formed by integrated HBV DNA with host genomic DNA was found in transcriptionally active regions. Furthermore, HBV infection influences host gene expression accompanied with HBV DNA–host DNA contacts. Our study provides a 3D landscape of spatial organization of cccDNA and integrated HBV DNA within the human genome, which lays the foundation for a better understanding of the mechanisms how HBV involves in liver disease development and progression.

scholarly journals Molecular Diagnosis in Differentiating Active and Inactive Forms of Hepatitis B Virus Carriers

2018 ◽  
Vol 26 (10) ◽  
pp. 41-45
Author(s):  
Salah Tofik Jalal Balaky ◽  
Saeed Ghulam Hussain ◽  
Amer Ali Khaleel ◽  
Furat Tahseen Sabeer ◽  
Ahang Hasan Mawlood
Keyword(s):  
Nucleic Acid ◽  
Hepatitis B ◽  
Cross Sectional Study ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Detection Methods ◽  
Rt Pcr ◽  
Cross Sectional ◽  
Blood Samples ◽  
Acid Test

Background & objectives: Introducing a nucleic acid test program is aimed to diagnose and reduces the risk of viral infection or transmission. DNA assay for HBV can detect infection in the windows period, chronic occult infection and can discriminate between active and inactive HBV infection. This cross-sectional study designed to diagnose, analyze HBV infection and to differentiate active from inactive infection based on viral DNA detection. Methods: Blood samples were collected from 256 patients previously diagnosed on the clinical ground as hepatitis B seropositive in Erbil Central Lab. The viral nucleic acid quantitative assessment was done for the collected samples using RT-PCR. Q-square was performed for statistical analysis. Results: Out of 256 collected blood samples 93 (36.3%) showed HBV-DNA positive titers above 50 IU/ml. Among positive subjects, 67 (72.04%) was categorized as inactive carriers (˂ 2000-20.000 IU/ml HBV-DNA titers). Conclusions: The data produced from this study confirmed the importance of the RT-PCR technique in sensitivity and reliability as a superior diagnostics tool specifically in differentiating active from inactive HBV carriers.

scholarly journals Endemic hepatitis B virus (HBV) among hospital in-patients in Bangladesh, including evidence of occult infection

2020 ◽  
Author(s):  
Fazle Rabbi Chowdhury ◽  
Anna L McNaughton ◽  
Mohammad Robed Amin ◽  
Lovely Barai ◽  
Mili Rani Saha ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Occult Hepatitis ◽  
Treatment And Prevention ◽  
B Virus ◽  
High Prevalence ◽  
Hospital Patients ◽  
Surface Gene

ABSTRACTBangladesh is one of the world’s top ten burdened countries for viral hepatitis. We investigated an adult fever cohort (n=201) recruited in Dhaka, to determine the prevalence of hepatitis B virus (HBV) infection and to identify cases of occult hepatitis B infection (OBI). HBV exposure (anti-HBc) was documented in 72/201 (36%), and active HBV infection in 16/201 (8%), among whom 3 were defined as OBI (defined as detectable HBV DNA but negative HBsAg). Applying a target-enrichment sequencing pipeline to samples with HBV DNA >3.0log10 IU/ml, we obtained deep whole genome sequences for four cases, identifying genotypes A, C and D. Polymorphisms in the surface gene of the OBI case may account for the negative HBsAg status. We identified mutations associated with nucleos(t)ide analogue resistance, although the clinical significance in this cohort is not known. The high prevalence of HBV in this setting highlights the benefits of offering screening in hospital patients and the importance of HBV DNA testing of transfusion products to reduce the risk of transmission. In order to work towards international Sustainable Development Goal targets for HBV elimination, increased investment is required for diagnosis, treatment and prevention in Bangladesh.

scholarly journals Primary Tupaia Javanica Hepatocyte Culture as an In Vitro Model for Human Hepatitis B Virus Infection

2022 ◽  
Vol 22 (3) ◽  
pp. 203-209
Author(s):  
Kemal Fariz Kalista ◽  
Maryati Surya ◽  
Silmi Mariya ◽  
Diah Iskandriati ◽  
Irsan Hasan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Vitro Model ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Primate Research ◽  
Qualitative And Quantitative ◽  
B Virus ◽  
Vitro Model

Background: Hepatitis B virus (HBV) infection is still one of the biggest health problems in the world, which could lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Treatment for HBV infection has not yet achieved a functional cure. More studies are needed to investigate human HBV (HuHBV), but the scarcity of animal models for HuHBV infection became a barrier. Recently, many studies have shown that Tupaia are suitable for the study of HuHBV. The purpose of this study was to develop a primary tupaia hepatocyte (PTH) culture from T. javanica, a species of Tupaia found in Indonesia, and to prove that HuHBV can replicate in the PTH.Method: In vitro experimental study using PTH isolated from five wild adult T. javanica in Primate Research Center, IPB University. HuHBV was taken from humans with HBsAg and HBV-DNA (+). PTH cells then were infected with HuHBV after reaching 80% confluence. Observation on PTH cells was done everyday for 20 days. Qualitative and quantitative HBsAg were measured using a CMIA while HBV-DNA and cccDNA were measured by RT-PCR.Results: A cytopathic effect was seen on day post infection (DPI)-16. HBsAg and HBV-DNA were detected from DPI-2 until DPI-18, with HBV-DNA level peaked on DPI-12. cccDNA concentration was fluctuating from DPI-2 until DPI-20 with highest level on DPI-16.Conclusion: HuHBV could infect and replicate in PTH from T. javanica can be infected with HuHBV and HuHBV can replicate in the PTH from T. javanica.

Antibodies to Hepatitis B Surface Antigen (HBsAb) Are Acquired after Allogeneic Stem Cell Transplantation in Non-B Hepatitis Virus-Infected Patients but Disappear over Time

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Jinhua Ren ◽  
Tingting Xiao ◽  
Yingxi Weng ◽  
Rong Zheng ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Hepatitis B ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hepatitis Virus ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hematopoietic Stem

BACKGROUND: There is currently no unified standard protocol for the prevention of hepatitis B virus (HBV) infection in patients with hematopoietic stem cell transplantation. The incidence of HBV infection is high in China, particularly in the Fujian Province of China. Nevertheless, there are also many transplanted patients who are not infected with HBV as indicated by serology markers (negative for HBsAg, anti-HBsAb, HBeAg, anti-HBeAb, anti-HBcAb, HBV-DNA). Therefore, there is a need to develop a protocol to prevent hepatitis virus infection in these non-infected patients. AIMS: This study aims to determine the changes in HBV immune status after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients not infected with HBV for establishing a management protocol to prevent HBV infection in these patients after allo-HSCT. METHODS: The study included 54 patients in non-B hepatitis virus-infected who received allo-HSCT at the Fujian Medical University Union Hospital between March 2013 and April 2020 for acute myeloid leukemia (n=22), acute lymphoblastic leukemia (n=18), chronic myeloid leukemia (n=3), aplastic anemia (n=5), lymphoma (n=2) and myelodysplastic syndrome (n=4). All patients were tested for hepatitis B serum markers by ELISA and HBV-DNA by PCR before and every 2 weeks after transplantation but did not receive hepatitis B immunoglobulin to prevent HBV infection. Four patients received Entecavir prophylactic antiviral therapy because the stem cells came from HBsAg positive donors (2 HBV-DNA negative, 2 HBV-DNA positive). Of the 50 HBsAg negative donors, 15 were anti-HBsAb negative, including 8 anti-HBcAb positive and 7 anti-HBcAb negative, and 35 were anti-HBsAb positive, of which 23 were anti-HBcAb positive and 12 anti-HBcAb negative. RESULTS: All 54 patients had changes in HBV immune status after allo-HSCT, including 48 cases positive for anti-HBsAb/anti-HBcAb (87.03%) and 7 cases positive for anti-HBsAb and negative for anti-HBcAb (12.96%). It means that all of these patients obtained protective antibodies against HBV. The median time (range) for HBV immune status changes was 5 (1-84) days after transplantation. The titer of HBsAb changed with immune reconstruction after transplantation. The median titers (mIU/ml) of HBsAb at Day 30, 60, 90, 120, 180 and 240 after transplantation were 258.49, 133.4, 33.17, 15.95, 26.89, and 27.99, respectively. On Day 30, 60, 90, 120, 180 and 240 post-transplantation, 18.91% (7/37), 41.17% (14/34), 50% (14/28), 72.2%, (13/18) of the anti-HBsAb and anti-HBcAb positive patients became negative. It means that these patients lost HbsAb but no new hepatitis B virus infection occurred during the median (range) follow-up of 299 (22-2572) days. CONCLUSIONS: After allo-HSCT, HBV-negative patients acquired HB surface antibodies, and the HBsAb titer gradually decreased to eventually disappear at the end of follow-up. Therefore, we do not recommend prophylactic anti-hepatitis B virus therapy in the early stage of hematopoietic stem cell transplantation in non-HBV infected patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study

2019 ◽  
Vol 69 (11) ◽  
pp. 1969-1979
Author(s):  
Willem P Brouwer ◽  
Henry L Y Chan ◽  
Pietro Lampertico ◽  
Jinlin Hou ◽  
Pisit Tangkijvanich ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Association Study ◽  
Chronic Hepatitis B ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Pegylated Interferon ◽  
Hbv Dna ◽  
Genome Wide Association ◽  
Genome Wide

AbstractBackground(Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand.MethodsIn this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients.ResultsOf 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= −0.74, standard error [SE] = 0.16, P = 3.44 ×10–6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10–6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele.ConclusionsAlthough no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies.Clinical Trials RegistationNCT01401400.

scholarly journals Diagnostic Value of Detection of Pregenomic RNA in Sera of Hepatitis B Virus-Infected Patients with Different Clinical Outcomes

2019 ◽  
Vol 58 (2) ◽  
Author(s):  
Ni Lin ◽  
Aizhu Ye ◽  
Jinpiao Lin ◽  
Can Liu ◽  
Jinlan Huang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Outcomes ◽  
Hepatitis B Surface Antigen ◽  
Surrogate Marker ◽  
Diagnostic Value ◽  
Hbv Dna ◽  
Hbv Cccdna ◽  
B Virus ◽  
Intrahepatic Hbv

ABSTRACT Pregenomic RNA (pgRNA) is a direct transcription product of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), and it plays important roles in viral genome amplification and replication. This study was designed to investigate whether serum pgRNA is a strong alternative marker for reflecting HBV cccDNA levels and to analyze the correlation between serum pgRNA, serum HBV DNA, and hepatitis B surface antigen (HBsAg). A total of 400 HBV-infected patients who received nucleos(t)ide analog (NA) therapy with different clinical outcomes were involved in this research. Case groups included asymptomatic hepatitis B virus carrier (ASC), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) patients, with 100 patients in each group. The results showed that the levels of HBV pgRNA had significant differences between these 4 groups. Serum pgRNA levels correlated well with serum HBV DNA and HBsAg levels (HBV pgRNA levels versus HBV DNA levels, r = 0.58, P < 0.001; HBV pgRNA levels versus HBsAg levels, r = 0.47, P < 0.001). In addition, we focused on the 108 HBV-infected patients with HBV DNA levels of <500 IU/ml; it was surprising to find that in 17.57% (13/74) of cases, HBV pgRNA could be detected even when the HBV DNA level was below 20 IU/ml. In conclusion, HBV pgRNA levels in serum can be a surrogate marker for intrahepatic HBV cccDNA compared with serum HBV DNA and HBsAg. The detection of serum HBV pgRNA levels may provide a reference for clinical monitoring of cccDNA levels and the selection of appropriate timing for discontinuing antiviral therapy, especially when HBV DNA levels are below the detection limit.

scholarly journals Spectrum of Hepatits B Infection Among Patients Attending Liver Unit in Nepalgunj Medical College – Kohalpur

2018 ◽  
Vol 16 (2) ◽  
pp. 2-5
Author(s):  
Dipendra Khadka ◽  
Sudhamshu KC ◽  
Niyanta Karki ◽  
Sandip Khadka ◽  
Kiran Regmi
Keyword(s):  
Liver Disease ◽  
Hepatitis B ◽  
Tertiary Care ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hepatitis B Infection ◽  
Chronic Hbv Infection ◽  
Medical College ◽  
Liver Unit ◽  
Chronic Hbv

Introduction: Hepatitis B infection is a global problem. Hepatitis B virus (HBV) infection related liver disease is also not an uncommon problem in our country too. Reports regarding pattern of chronic HBV infection are also lacking. The aim of the present study was to determine the spectrum of chronic HBV infection among patients attending the liver clinic in a tertiary care center. Method: A hospital based descriptive cross-sectional study was carried out in Liver unit of Nepalgunj Medical College, Kohalpur, from April 2018 to November 2018. All patients with HBsAg positive were further tested for HBeAg, HBeAb, HBV DNA quantitative and liver function test. Ultrasound examination was advised for any evidence of chronic liver disease. Staging was done according to viral serology, liver biochemistry and ultrasonography of liver Results: Total patients enrolled were 119. Majority of patents were in between 30-60 years (51.3%) with male predominance 59.7%. Most of patients were in the stage of HBeAg negative chronic infection 66.4% with normal transaminase and HBV DNA <2000 IU/ML. Majority of patients having unknown source of infection 90.8%. Incidental detection (67.2%) was common mode of detection. Conclusions: Majority of patients were in HBeAg negative chronic hepatitis B infection phase with normal transaminase and low HBV DNA not requiring treatment.

The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2419-2425 ◽  
Author(s):  
Jean-Pierre Allain ◽  
Daniel Candotti ◽  
Kate Soldan ◽  
Francis Sarkodie ◽  
Bruce Phelps ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Blood Donors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Sub Saharan Africa ◽  
B Virus ◽  
Sub Saharan ◽  
Hbv Transmission

The risk of hepatitis B virus (HBV) transmission by transfusion in sub-Saharan Africa is considered to be relatively low, and testing of blood donors is often not done or is done relatively poorly. To re-examine this attitude, we identified HBV chronically infected blood donors from a major hospital in Ghana with a range of hepatitis B surface antigen (HBsAg) assays. Test efficacy was estimated using HBV DNA as a gold standard, and the risk of HBV infection in blood recipients was estimated for different testing strategies. Particle agglutination, dipstick, and enzyme immunoassay (EIA) HBsAg screening detected 54%, 71%, and 97% of HBV infectious donors, respectively. The risk of HBV transmission to recipients less than 10 years old ranged between 1:11 and 1:326 with blood unscreened and screened by EIA, respectively. For older recipients, the risk decreased a further 4-fold because of the high frequency of natural exposure to HBV. A total of 98% of HBsAg-confirmed positive samples contained HBV DNA. HBV DNA load was less than 1 × 104 IU/mL in 75% of HBsAg-reactive samples, most of them anti-HBe reactive. Approximately 0.5% of HBsAg-negative but anti-HBc-positive samples contained HBV DNA. The use of sensitive HBsAg tests is critical to prevent transfusion transmission of HBV infection to young children in a population with a 15% prevalence of chronic HBV infection in blood donors. However, this will not have much effect on the prevalence of this infection unless other strategies to protect children from infection are also advanced in parallel.

scholarly journals Mapping the Interactions of HBV cccDNA with Host Factors

2019 ◽  
Vol 20 (17) ◽  
pp. 4276 ◽  
Author(s):  
Mohd-Ismail ◽  
Lim ◽  
Gunaratne ◽  
Tan
Keyword(s):  
Hepatitis B ◽  
Hbv Infection ◽  
Host Factors ◽  
Major Health Problem ◽  
Major Health ◽  
Cellular Processes ◽  
Hbv Replication ◽  
Hbv Cccdna ◽  
B Virus ◽  
Surrogate Systems

Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has reduced new infections, a cure for chronic hepatitis B (CHB) is still unavailable. Current anti-HBV therapies slow down disease progression but are not curative as they cannot eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The cccDNA minichromosome persists in the nuclei of infected hepatocytes where it forms the template for all viral transcription. Interactions between host factors and cccDNA are crucial for its formation, stability, and transcriptional activity. Here, we summarize the reported interactions between HBV cccDNA and various host factors and their implications on HBV replication. While the virus hijacks certain cellular processes to complete its life cycle, there are also host factors that restrict HBV infection. Therefore, we review both positive and negative regulation of HBV cccDNA by host factors and the use of small molecule drugs or sequence-specific nucleases to target these interactions or cccDNA directly. We also discuss several reporter-based surrogate systems that mimic cccDNA biology which can be used for drug library screening of cccDNA-targeting compounds as well as identification of cccDNA-related targets.

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