the Study of Hepatitis B Virus Reactivation

Hepatitis B virus(HBV) reactivation after chemotherapy or immunosuppressive therapy is a cause of liver-related morbidity and mortality. Not all chronic hepatitis B patients will lead to HBV reactivation. The incidence is 0.3%-30.2% according to the reports. The mechanism of HBV reactivation is still unclear, but it is believed that the viral load is increasing due to the suppression of immune response. No uniform diagnostic criteria are available. HBV reactivation can be confirmed by an increase of serum HBV DNA level. Recently, awareness of reactivation of occult HBV has been improved, especially in HBV endemic area. Preemptive antiviral therapy was the best approach to prevent the HBV reactivation. HBV reactivation can lead to acute hepatitis, severe hepatitis and acute liver failure. Therefore, it is worthy of great attention and further study. Antiviral therapy is safe and effective to prevent HBV reactivation.

Hepatitis B Reactivation with Novel Agents in Non-Hodgkin's Lymphoma and Prevention Strategies

Hepatitis B virus (HBV) infection remains an endemic disease in most parts of the world despite available prophylactic vaccines.Non-Hodgkin's lymphoma is the most common hematological malignancy,and certain patients undergoing therapy are at increased risk of HBV reactivation.Rituximab,a monoclonal antibody,is well studied in HBV reactivation,but newer agents have been implicated as well.Here,we review novel agents suspected in HBV reactivation and effective strategies to prevent HBV reactivation.Fifteen years of literature were reviewed in order to better understand the reactivation rates of hepatitis B in patients with non-Hodgkin's lymphoma.Anti-CD20 antibodies continue to be the main medications that can lead to HBV reactivation,and HBV reactivation rates have decreased with increased awareness.HBV reactivation is uncommon when using other novel agents.Entecavir and lamivudine remain the agents of choice to prevent HBV reactivation in high risk patients.In conclusion,the immunosuppressive effect of NHL and its therapy provide a pathway for HBV reactivation,especially in patients treated with anti-CD20 antibody.Since many HBV positive patients are often excluded from clinical trials of novel agents in NHL,more aggressive post-market surveillance of new agents,welldesigned best practice advisories,and timely case reports are needed to reduce the incidence of HBV reactivation.Lastly,large prospective investigations coupled with well-utilized best practice advisories need to be conducted to understand the impact of more potent novel NHL therapy on HBV reactivation.(C) 2016 The Second Affiliated Hospital of Chongqing Medical University.Published by XIA & HE Publishing Inc.All rights reserved.

Histone Deacetylase Inhibitors Romidepsin and Vorinostat Promote Hepatitis B Virus Replication by Inducing Cell Cycle Arrest

Background and Aims:Chronic hepatitis B virus(HBV)infection is a global public health challenge.HBV reactivation usually occurs in cancer patients after receiving cytotoxic chemotherapy or immunosuppressive therapies.Romidepsin(FK228)and vorinostat(SAHA)are histone deacetylase inhibitors(HDACi)approved by the Food and Drug Administration as novel antitumor agents.The aim of this study was to explore the effects and mechanisms of HDACi treatment on HBV replication.Methods:To assess these effects,human hepatoma cell lines were cultured and cell viability after FK228 or SAHA treatment was measured by the CCK-8 cell counting kit-8 assay.Then,HBV DNA and RNA were quantified by real-time PCR and Southern blotting.Furthermore,analysis by western blotting,enzyme-linked immunosorbent assay(ELISA),immunohistochemistry,and flow cytometry was performed.Results:FK228/SAHA treatment significantly promoted HBV replication and biosynthesis in both HBV-replicating cells and HBV-transgenic mouse model.Flow cytometry assay indicated that FK228/SAHA enhanced HBV replication by inducing cell cycle arrest through modulating the expression of cell cycle regulatory proteins.In addition,simultaneous inhibition of HDAC1/2 by FK228 promoted HBV replication more effectively than the broad spectrum HDAC inhibitor SAHA.Conclusions:Overall,our results demonstrate that cell cycle blockage plays an important role in FK228/SAHAenhanced HBV replication,thus providing a potential avenue for rational use of HDACi in patients with chronic hepatitis B.

The dilemma of cytomegalovirus and hepatitis B virus interaction

Hepatitis B virus(HBV)remains a global public health problem despite the availability of effective vaccine and antiviral therapy.Cytomegalovirus(CMV),another hepatotropic virus,is also very prevalent in the general population worldwide.Both HBV and CMV can persist in the host and have potential to reactivate especially with weakened host cellular immunity.Superimposed CMV infection can lead to severe HBV reactivation.The pathogenesis of the co-infection of HBV and CMV remains poorly understood.Studies reported conflicting results regarding the inhibitory effect of CMV on HBV replication.There is an unmet need on the management of co-infection of HBV and CMV;research initiatives dedicated to understanding their interactions are urgently needed.