scholarly journals Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update

2021 ◽  
Vol 10 (12) ◽  
pp. 2564
Author(s):  
Cristina Stasi ◽  
Giacomo Tiengo ◽  
Sinan Sadalla ◽  
Anna Linda Zignego
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immunosuppressive Therapy ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Close Monitoring ◽  
Occult Hbv ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.

scholarly journals Transcriptional Elongation Control of Hepatitis B Virus Covalently Closed Circular DNA Transcription by Super Elongation Complex and BRD4

2017 ◽  
Vol 37 (19) ◽  
Author(s):  
Joel Celio Francisco ◽  
Qian Dai ◽  
Zhuojuan Luo ◽  
Yan Wang ◽  
Roxanne Hui-Heng Chong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Intermediate Step ◽  
Hbv Reactivation ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Super Elongation Complex ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of the HBV life cycle. However, factors controlling HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the super elongation complex (SEC) bind to the HBV genome. The treatment of bromodomain inhibitor JQ1 stimulates HBV transcription and increases the occupancy of BRD4 on the HBV genome, suggesting the bromodomain-independent recruitment of BRD4 to the HBV genome. JQ1 also leads to the increased binding of SEC to the HBV genome, and SEC is required for JQ1-induced HBV transcription. These findings reveal a novel mechanism by which the HBV genome hijacks the host P-TEFb-containing complexes to promote its own transcription. Our findings also point out an important clinical implication, that is, the potential risk of HBV reactivation during therapy with a BRD4 inhibitor, such as JQ1 or its analogues, which are a potential treatment for acute myeloid leukemia.

scholarly journals Pleural Effusion Related to Chronic Hepatitis B Virus Reactivation: A Rare Association

2021 ◽  
Author(s):  
Ana Oliveira ◽  
Diana Valadares ◽  
Filipe Nery
Keyword(s):  
Hepatitis B Virus ◽  
Pleural Effusion ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Viral Reactivation ◽  
Major Public Health Problem ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Despite worldwide vaccination campaigns, hepatitis B virus (HBV) infection remains a major public health problem. The natural history ranges from asymptomatic infection to severe liver injury or failure, chronic complications or reactivation episodes. The effects of HBV on the organism are immunomediated, possibly triggering extrahepatic manifestations. Since 1971, only a few cases of pleural effusion related to HBV infection have been described. We report HBV-associated pleural effusion occurring during a viral reactivation episode. Antiviral treatment directed towards pleural effusion related to HBV infection should be dictated by underlying liver disease severity and not pleural effusion severity.

scholarly journals The efficacy of lamivudine in the treatment of reactivation of chronic hepatitis B virus infection in patients on immunosuppressive therapy

2011 ◽  
Vol 139 (11-12) ◽  
pp. 824-827
Author(s):  
Natasa Popovic ◽  
Neda Stojkovic-Svirtlih ◽  
Jasmina Simonovic-Babic ◽  
Ivan Boricic ◽  
Nada Tomanovic ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immunosuppressive Therapy ◽  
Chronic Hepatitis B ◽  
Aminotransferase Level ◽  
Hbv Reactivation ◽  
Hepatitis B Virus Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Introduction. Reactivation of chronic hepatitis B virus (HBV) infection often occurs in hepatitis B surface antigen (HBsAg) positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy. Outline of Cases. The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient?s recovery and allowed further chemotherapy. Conclusion. In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

scholarly journals ATM and ATR Expression Potentiates HBV Replication and Contributes to Reactivation of HBV Infection upon DNA Damage

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 997 ◽  
Author(s):  
Anastasiya Kostyusheva ◽  
Sergey Brezgin ◽  
Ekaterina Bayurova ◽  
Ilya Gordeychuk ◽  
Maria Isaguliants ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Mrna Levels ◽  
Hbv Replication ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus infection (CHB) caused by the hepatitis B virus (HBV) is one of the most common viral infections in the world. Reactivation of HBV infection is a life-threatening condition observed in patients with CHB receiving chemotherapy or other medications. Although HBV reactivation is commonly attributed to immune suppression, other factors have long been suspected to play a role, including intracellular signaling activated in response to DNA damage. We investigated the effects of DNA-damaging factors (doxorubicin and hydrogen peroxide) on HBV reactivation/replication and the consequent DNA-damage response. Dose-dependent activation of HBV replication was observed in response to doxorubicin and hydrogen peroxide which was associated with a marked elevation in the mRNA levels of ataxia-telangiectasia mutated (ATM) and ATM- and RAD3-related (ATR) kinases. Downregulation of ATM or ATR expression by shRNAs substantially reduced the levels of HBV RNAs and DNA. In contrast, transcriptional activation of ATM or ATR using CRISPRa significantly increased HBV replication. We conclude that ATM and ATR are essential for HBV replication. Furthermore, DNA damage leading to the activation of ATM and ATR transcription, results in the reactivation of HBV replication.

scholarly journals Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis

2020 ◽  
Vol 8 (10) ◽  
pp. 1470
Author(s):  
Keith C.K. Lau ◽  
Kelly W. Burak ◽  
Carla S. Coffin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Lymphoid Cells ◽  
Hbv Infection ◽  
Dynamic Nature ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Chronic Hbv

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.

scholarly journals Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV)

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 850 ◽  
Author(s):  
Mariantonietta Pisaturo ◽  
Margherita Macera ◽  
Loredana Alessio ◽  
Federica Calò ◽  
Nicola Coppola
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Clinical Event ◽  
Hbv Reactivation ◽  
Occult Hbv Infection ◽  
Occult Hbv ◽  
B Virus

The US Food and Drug Administration issued a black box warning related to the risk of reactivation of overt/occult hepatitis B virus (HBV) infection during direct acting-antivirals (DAA) treatment. This review evaluated the prevalence of HBV reactivation after hepatitis C virus (HCV) pharmacological suppression and hypothesized the management and prevention of this reactivation. During and after DAA-based treatment, reactivation of HBV infection is common in patients with detectable serum HBsAg (from 2% to 57%) and very low (less than 3%) in individuals with isolated anti-HBc antibodies. The severity of hepatic damage may range from HBV reactivation without hepatitis to fulminant hepatic failure requiring liver transplantation. Thus, HBsAg-positive patients should receive nucleo(s)tide analog (NA) treatment or prophylaxis at the same time as DAA therapy. For those patients with occult B infection, there are no sufficient recommendations to start prophylactic treatment. Reactivation of overt or occult HBV infection during or after eradication of HCV infection is an issue to consider, and additional studies would help to determine the best management of this virological and clinical event.

scholarly journals Antiviral Treatment among Hepatitis B Virus-Infected Pregnant Women—New York City and Michigan, 2013–2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S41-S41
Author(s):  
Ruth Link-Gelles ◽  
Alaya Koneru ◽  
Julie Lazaroff ◽  
Patrick Fineis ◽  
Noele Nelson ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnant Women ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Maternal Treatment ◽  
Increased Risk ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Hbv Transmission

Abstract Background Individuals with chronic hepatitis B virus (HBV) infection are at increased risk for cirrhosis and hepatocellular carcinoma. Chronic HBV infection develops in 90% of persons infected at birth. Although postexposure prophylaxis (PEP), consisting of hepatitis B vaccine and immune globulin at birth, and completion of the three-dose vaccine series prevents up to 95% of perinatal HBV infections; however, breakthrough infections can occur, especially among infants born to women with high viral loads (VLs). Maternal antiviral treatment during pregnancy can reduce perinatal HBV transmission by 70% above the effect of infant PEP alone. We assessed factors associated with maternal antiviral treatment in a cohort of HBV-infected pregnant women with high VL. Methods During 2013–2015, the CDC-funded Supplemental Perinatal Hepatitis B Prevention Program collected information from interviews and medical charts of HBV-infected pregnant women in two sites. We assessed the association of demographic and clinical factors with maternal treatment in women with high VL (>200,000 IU/mL), considering statistical significance at P < 0.05. Results Among 1,521 women with maternal treatment and VL data, 151 (10%) had high VL. Among these 151 women, 66 (44%) received antiviral treatment (Table), all of whom were of Asian/Pacific Island race. None of the seven women of other races were treated (P = 0.02). Fifty-nine women (48%) receiving Medicaid were treated compared with six women (24%) who had private insurance (P = 0.04). Conclusion Mother’s race, country of birth, and insurance status were significantly associated with treatment in women with high VL. Because most women with high VL did not receive antiviral treatment during pregnancy, opportunities to reduce perinatal HBV transmission exist. Disclosures All authors: No reported disclosures.

High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection

2013 ◽  
Vol 62 (8) ◽  
pp. 1235-1238 ◽  
Author(s):  
Inmaculada Castillo ◽  
Javier Bartolomé ◽  
Juan Antonio Quiroga ◽  
Vicente Carreño
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hcv Infection ◽  
Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

scholarly journals Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Artificial Transcription Factor ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

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