The Role of Integrated HBV DNA in the Quest for a Cure in HIV/HBV co-infection.
This review highlights the importance of Hepatitis B virus (HBV) integrated into the host genome (iDNA) to functional cure and how human immunodeficiency virus (HIV) may affect HBV integration. Functional cure of chronic hepatitis B infection is characterized by durable loss of hepatitis B surface antigen (HBsAg) from blood after treatment discontinuation. Because HBsAg is transcribed from two intrahepatic sources, covalently closed circular DNA (cccDNA) or iDNA, functional cure requires elimination or silencing of both sources. It is not clear how HIV affects HBV integration, but since HIV enhances HBV replication and leads to increased DNA breaks through oxidative stress, people with HIV and HBV may have more integration events. HBV integration into the human genome is a random and ongoing process that occurs during all phases of chronic HBV infection (CHB). iDNA is important for maintaining HBsAg expression despite antiviral therapy. In studies without HIV, higher levels of HBV replication are associated with increased integration events. Higher HBV DNA levels in HIV/HBV co-infected individuals may contribute to increased HBV integration. HIV worsens CHB by weakening immune responses, promoting oxidative stress, and activating cellular pathways that enhance HBV replication and integration.
- # Hepatitis B Virus Integration
- # How Human Immunodeficiency Virus
- # Hepatitis B Virus
- # Phases Of Chronic Hepatitis B Virus Infection
- # Enhance Hepatitis B Virus Replication
- # Higher Hepatitis B Virus DNA Levels
- # Hepatitis B Surface Antigen
- # Hepatitis B Virus Replication
- # Hepatitis B Virus DNA
- # Intrahepatic Sources
39
- 10.1016/j.jhep.2020.12.034
- Jan 29, 2021
- Journal of Hepatology
25
- 10.1002/hep.31902
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- Hepatology
458
- 10.1002/hep.510290447
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- Hepatology
412
- 10.1126/scitranslmed.aan0241
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155
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8
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1807
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176
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176
- 10.1073/pnas.0403925101
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194
- 10.1016/j.jhep.2005.02.005
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The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma
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- 10.1097/mcg.0b013e3182a6633d
- Jan 1, 2014
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Impact of Occult Hepatitis B Virus Infection or Hepatitis B Virus DNA Integration on Efficacy of Chronic Hepatitis C Treatment With Peginterferon and Ribavirin
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133
- 10.1111/j.1440-1797.2009.01268.x
- Mar 1, 2010
- Nephrology
The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy.
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211
- 10.1053/j.gastro.2007.09.002
- Sep 6, 2007
- Gastroenterology
Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease in HBeAg-Negative Patients
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- 10.1053/j.gastro.2004.12.007
- Mar 1, 2005
- Gastroenterology
RNA interference-mediated control of hepatitis B virus and emergence of resistant mutant
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468
- 10.1002/hep.21051
- Jan 1, 2006
- Hepatology
Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy
- Discussion
8
- 10.1053/j.gastro.2003.05.011
- Dec 1, 2003
- Gastroenterology
Occult HBV infection—both hidden and mysterious
- Research Article
103
- 10.1046/j.1440-1746.2003.03037.x
- Feb 26, 2003
- Journal of Gastroenterology and Hepatology
Large amounts of new data on the natural his- tory and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/ naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated inter- feron a2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier ''Asian-Pacific consen- sus statement on the management of chronic hepatitis B''
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147
- 10.1016/j.jhep.2010.12.030
- Jan 14, 2011
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Natural history of chronic hepatitis B in Euro-Mediterranean and African Countries
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24
- 10.1016/j.jhep.2005.01.003
- Jan 22, 2005
- Journal of Hepatology
Time-dependent events in natural history of occult hepatitis B virus infection: the importance of population-based long-term follow-up study with repeated measurements
- Front Matter
19
- 10.1053/j.gastro.2019.01.015
- Jan 11, 2019
- Gastroenterology
Hepatitis B Surface Antigen Loss: Too Little, Too Late and the Challenge for the Future
- Front Matter
5
- 10.1016/s0168-8278(03)00156-9
- Apr 25, 2003
- Journal of Hepatology
Treatment options for chronic hepatitis B not responding to interferon
- Supplementary Content
2
- 10.3389/fmicb.2024.1469016
- Sep 6, 2024
- Frontiers in Microbiology
The integration of Hepatitis B Virus (HBV) is now known to be closely associated with the occurrence of liver cancer and can impact the functionality of liver cells through multiple dimensions. However, despite the detailed understanding of the characteristics of HBV integration and the mechanisms involved, the subsequent effects on cellular function are still poorly understood in current research. This study first systematically discusses the relationship between HBV integration and the occurrence of liver cancer, and then analyzes the status of the viral genome produced by HBV replication, highlighting the close relationship and structure between double-stranded linear (DSL)-HBV DNA and the occurrence of viral integration. The integration of DSL-HBV DNA leads to a certain preference for HBV integration itself. Additionally, exploration of HBV integration hotspots reveals obvious hotspot areas of HBV integration on the human genome. Virus integration in these hotspot areas is often associated with the occurrence and development of liver cancer, and it has been determined that HBV integration can promote the occurrence of cancer by inducing genome instability and other aspects. Furthermore, a comprehensive study of viral integration explored the mechanisms of viral integration and the internal integration mode, discovering that HBV integration may form extrachromosomal DNA (ecDNA), which exists outside the chromosome and can integrate into the chromosome under certain conditions. The prospect of HBV integration as a biomarker was also probed, with the expectation that combining HBV integration research with CRISPR technology will vigorously promote the progress of HBV integration research in the future. In summary, exploring the characteristics and mechanisms in HBV integration holds significant importance for an in-depth comprehension of viral integration.
- Preprint Article
15
- 10.2450/2011.0046-11
- Nov 15, 2011
- Blood transfusion = Trasfusione del sangue
Low frequency of occult hepatitis B infection in anti-HBc seropositive blood donors: experience from a tertiary care centre in South India.
- Research Article
33
- 10.3350/cmh.2020.0115
- Dec 3, 2020
- Clinical and Molecular Hepatology
Background/AimsThe role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.MethodsUsing probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.ResultsHBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.ConclusionsThe biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAg-serocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.
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