scholarly journals Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma

2015 ◽  
Vol 35 (10) ◽  
pp. 2311-2317 ◽  
Author(s):  
Carlo Saitta ◽  
Gianluca Tripodi ◽  
Adalberto Barbera ◽  
Antonio Bertuccio ◽  
Antonina Smedile ◽  
...  
Vox Sanguinis ◽  
2008 ◽  
Vol 95 (3) ◽  
pp. 174-180 ◽  
Author(s):  
K. Satoh ◽  
A. Iwata-Takakura ◽  
A. Yoshikawa ◽  
Y. Gotanda ◽  
T. Tanaka ◽  
...  

2018 ◽  
Vol 92 (11) ◽  
pp. e02007-17 ◽  
Author(s):  
Thomas Tu ◽  
Magdalena A. Budzinska ◽  
Florian W. R. Vondran ◽  
Nicholas A. Shackel ◽  
Stephan Urban

ABSTRACTChronic infection by hepatitis B virus (HBV) is the major contributor to liver disease worldwide. Though HBV replicates via a nuclear episomal DNA (covalently closed circular DNA [cccDNA]), integration of HBV DNA into the host cell genome is regularly observed in the liver in infected patients. While reported as a prooncogenic alteration, the mechanism(s) and timing of HBV DNA integration are not well understood, chiefly due to the lack ofin vitroinfection models that have detectable integration events. In this study, we have established anin vitrosystem in which integration can be reliably detected following HBV infection. We measured HBV DNA integration using inverse nested PCR in primary human hepatocytes, HepaRG-NTCP, HepG2-NTCP, and Huh7-NTCP cells after HBV infection. Integration was detected in all cell types at a rate of >1 per 10,000 cells, with the most consistent detection in Huh7-NTCP cells. The integration rate remained stable between 3 and 9 days postinfection. HBV DNA integration was efficiently blocked by treatment with a 200 nM concentration of the HBV entry inhibitor Myrcludex B, but not with 10 μM tenofovir, 100 U of interferon alpha, or a 1 μM concentration of the capsid assembly inhibitor GLS4. This suggests that integration of HBV DNA occurs immediately after infection of hepatocytes and is likely independent ofde novoHBV genome replication in this model. Site analysis revealed that HBV DNA integrations were distributed over the entire human genome. Further, integrated HBV DNA sequences were consistent with double-stranded linear HBV DNA being the major precursor. Thus, we have established anin vitrosystem to interrogate the mechanisms of HBV DNA integration.IMPORTANCEHepatitis B virus (HBV) is a common blood-borne pathogen and, following a chronic infection, can cause liver cancer and liver cirrhosis. Integration of HBV DNA into the host genome occurs in all known members of theHepadnaviridaefamily, despite this form not being necessary for viral replication. HBV DNA integration has been reported to drive liver cancer formation and persistence of virus infection. However, when and the mechanism(s) by which HBV DNA integration occurs are not clear. In this study, we have developed and characterized anin vitrosystem to reliably detect HBV DNA integrations that result from a true HBV infection event and that closely resemble those found in patient tissues. Using this model, we showed that integration occurs when the infection is first established. Importantly, we provide here a system to analyze molecular factors involved in HBV integration, which can be used to develop strategies to halt its formation.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4816-4816 ◽  
Author(s):  
Emilio Iannitto ◽  
Viviana Minardi ◽  
Giuseppina Calvaruso ◽  
Antonino Mulè ◽  
Donatella Ferraro ◽  
...  

Abstract Reactivation of hepatitis B virus infection in subjects receiving cytotoxic treatment for haematological malignancies occurs in 21–53% of chronic HBsAg carriers and in an unknown number of HBsAg negative subjects harbouring occult HBV infection. Immunotherapy with alemtuzumab, a humanized monoclonal antibody against CD52 on lymphoid cells, produces deep immunosuppression. We describe two subjects with chronic lymphocytic leukaemia and occult HBV infection who developed a virological and biochemical flare of hepatitis B following immunotherapy with alemtuzumab. One of them developed a full blown hepatitis with seroreversion from anti-HBs to HBsAg after four weeks of alemtuzumab. Lamivudine (100 mg die) achieved a complete clinical recovery and HBV-DNA clearance from blood within 8 weeks. The second patient (HBsAg and HBV-DNA seronegative, anti-HBs and anti-HBc positive before treatment) was kept under prophylaxis with lamivudine up to three months after alemtuzumab. Two months after withdrawal of lamivudine, clinical and laboratory features of acute hepatitis B developed. Lamivudine therapy was restarted and obtained a prompt recovery with HBsAg and HBV-DNA clearance. These cases suggest that alemtuzumab, as all other immune response modifiers, should be used cautiously when HBV infection is present. While a recommendation for universal pre-emptive treatment with lamivudine of all HBsAg positive patients undergoing effective immunosuppressive treatment can be made it is more difficult to establish a pattern for patients who have serological markers of previous HBV infection (anti-HBs and/or anti-HBc) and even more for those with no HBV markers. Testing for HBV-DNA in serum by highly sensitive PCR may discover up to 50% of these cases, allowing preemptive lamivudine therapy. A substantial proportion would however go undiscovered in the absence of a liver biopsy, which is clearly an unfeasible proposition as a screening procedure. Once a reactivation has been documented, nucleoside analog therapy should last for a few months after HBV-DNA clearance.


2010 ◽  
Vol 202 (5) ◽  
pp. 700-704 ◽  
Author(s):  
Pushpinder Kaur ◽  
Anupam Paliwal ◽  
David Durantel ◽  
Pierre Hainaut ◽  
Jean‐Yves Scoazec ◽  
...  

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Akrami ◽  
Mohammad Rafiee Monjezi ◽  
Shahrzad Ilbeigi ◽  
Farshid Amiri ◽  
Mohammad Reza Fattahi

: Hepatitis B virus [HBV], the best-described hepadnavirus, distributed all around the world and may lead to chronic and acute liver disease, cirrhosis, and hepatocellular carcinoma. Despite the advancement in treatment against HBV, an error-prone reverse transcriptase which is require for HBV replication as well as host immune pressure lead to constant evolution and emergence of genotypes, sub-genotypes and mutant viruses; so, HBV will be remained as a major healthcare problem around the world. This review article mainly focuses on the HBV mutations which correlated to occult HBV infection, Immune scape, vaccine failure and eventually liver cirrhosis and HCC. Current study indicated that preS/S region mutations are related to vaccine failure, immune escape, occult HBV infection and the occurrence of HCC. Whereas, P region Mutations may lead to drug resistance to NA antivirals. PreC/C region mutations are associated to HBeAg negativity, immune escape, and persistent hepatitis. Moreover, X region Mutations play an important role in HCC development.


2011 ◽  
Vol 35 (8-9) ◽  
pp. 554-559 ◽  
Author(s):  
M.K. Arababadi ◽  
A.A. Pourfathollah ◽  
A. Jafarzadeh ◽  
G. Hassanshahi ◽  
M. Salehi ◽  
...  

2016 ◽  
Vol 35 (2) ◽  
pp. 47
Author(s):  
Somying Ngamurulert ◽  
Isaya Janwithayanuchit ◽  
Sumonrat Chuwongwattana ◽  
Suda Louisirirotchanakul ◽  
Prasert Auewarakul

Objective: To investigate the prevalence of hepatitis B virus (HBV) infection and to diagnose an occult HBV infection in healthy Thai subjects after implementation of the expanded program on immunization (EPI) in newborns.Material and Method: The detection of HBsAg, anti-HBs and anti-HBc was done from serum samples of 5,886 healthy first year students from Huachiew Chalermprakiet University collected between 2009-2011 by immunochro-matography rapid assay (Alcon, USA). In case of only anti-HBc positive, the results were confirmed with chemiluminescence enzyme immunoassay (EIA) method and then they were investigated further for HBV occult infection by nested polymerase chain reaction technique.Results: A total of 78% (4,593/5,886) healthy first year students who had been vaccinated with HBV vaccine since birth were found to have no HBV markers, while 18.4% (1,083/5,886) had only anti-HBs. The prevalence of infection was 3.6% (210/5,886). Identification of patterns of HBV infection among the 210 infected subjects found that (1) Immuned due to past infection was 61.9% (130/210) (2) Infected with hepatitis B virus was 38.1% (80/120). The prevalence of both HBsAg and anti-HBc was 28.6% (60/210), while the prevalences of HBsAg and Anti-HBc alone were 3.8% (8/210) and 5.7% (12/210), respectively. Anti-HBc alone group was repeated with chemiluminescence EIA and HBV DNA was negative.Conclusion: The prevalence of HBV infection was 3.6% (210/5,886), however, seropositive rate of HBV infection was 1.4% (80/5,886). Most antibodies from vaccination had substantially declined to the point that it was undetectable. Therefore, the overall study showed an effective implementation of EPI in newborns. 


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