scholarly journals Novel Therapies of Hepatitis B and D

2021 ◽  
Vol 9 (12) ◽  
pp. 2607
Author(s):  
Iman Waheed Khan ◽  
Mati Ullah Dad Ullah ◽  
Mina Choudhry ◽  
Mukarram Jamat Ali ◽  
Muhammad Ashar Ali ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Therapeutic Agents ◽  
Hbv Infection ◽  
Public Health Issue ◽  
Global Public Health ◽  
Small Interfering Rnas ◽  
Hepatitis D ◽  
Current Therapies ◽  
Novel Therapeutic

Hepatitis B virus (HBV) infection is a global public health issue and is a major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis D virus (HDV) requires the hepatitis B surface antigen (HBsAg) to replicate. The eradication of HBV, therefore, can also cure HDV. The current therapies for chronic hepatitis B and D are suboptimal and cannot definitely cure the viruses. In order to achieve functional or complete cure of these infections, novel therapeutic agents that target the various sites of the viral replicative cycle are necessary. Furthermore, novel immunomodulatory agents are also essential to achieve viral clearance. Many of these new promising compounds such as entry inhibitors, covalently closed circular DNA (cccDNA) inhibitors, small interfering RNAs (siRNAs), capsid assembly modulators and nucleic acid polymers are in various stages of clinical developments. In this review article, we provided a comprehensive overview of the structure and lifecycle of HBV, the limitations of the current therapies and a summary of the novel therapeutic agents for both HDV and HBV infection.

scholarly journals Transaminase Elevations during Treatment of Chronic Hepatitis B Infection: Safety Considerations and Role in Achieving Functional Cure

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 745
Author(s):  
Andrew Vaillant
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Normal Liver ◽  
Hbv Infection ◽  
Functional Cure ◽  
Chronic Hbv Infection ◽  
New Therapies ◽  
Current Therapies ◽  
Chronic Hbv ◽  
Safety Considerations

While current therapies for chronic HBV infection work well to control viremia and stop the progression of liver disease, the preferred outcome of therapy is the restoration of immune control of HBV infection, allowing therapy to be removed while maintaining effective suppression of infection and reversal of liver damage. This “functional cure” of chronic HBV infection is characterized by the absence of detectable viremia (HBV DNA) and antigenemia (HBsAg) and normal liver function and is the goal of new therapies in development. Functional cure requires removal of the ability of infected cells in the liver to produce the hepatitis B surface antigen. The increased observation of transaminase elevations with new therapies makes understanding the safety and therapeutic impact of these flares an increasingly important issue. This review examines the factors driving the appearance of transaminase elevations during therapy of chronic HBV infection and the interplay of these factors in assessing the safety and beneficial nature of these flares.

scholarly journals Cross-sectional hospital-based study on the seroprevalence of hepatitis B virus markers among healthcare workers, NWR, Cameroon

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e045716
Author(s):  
Etheline W Akazong ◽  
Christopher Tume ◽  
Lawrence Ayong ◽  
Richard Njouom ◽  
Sebastien Kenmoe ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Healthcare Workers ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Public Health Issue ◽  
Past Infection ◽  
Cross Sectional ◽  
North West ◽  
B Virus

BackgroundHepatitis B virus (HBV) infection is a major public health issue worldwide, with about 257 million people reported to be chronic carriers by the WHO fact sheet updated in 2018. HBV can be contracted via direct contact with infected body fluid and infection is almost always asymptomatic. Although healthcare workers (HCWs) are at high risk of HBV infection, little is known about the prevalence of the various HBV markers among HCWs in Cameroon. The present study was taken to evaluate the prevalence of different HBV serological markers among HCWs in the North-West Region of Cameroon.MethodsThis cross-sectional hospital-based study was carried out between April and September 2017 during which 395 HCWs were recruited. The serum of the HCWs were tested for the presence of HBV core antibody, hepatitis B surface antibody, hepatitis B e antibody and hepatitis B surface antigen using Monalisa ELISA kits produced by BIO-RAD laboratories. Data were analysed using SPSS V.20.0.ResultsAmong the 395 participants, 270 (68.4%) of them were females, 187 (47.3%) had been exposed to HBV, 145 (36.7%) had resolved the infection, 42 (10.6%) were current HBV carriers, 10 (2.5%) were infective, 36 (9.1%) were vaccinated and 172 (43.5%) were still susceptible. Exposure to HBV, past infection and susceptibility were significantly associated with age while the rate of vaccination was significantly associated with the job of the HCW in the health facilities.ConclusionThe prevalence of HBV exposure and infection among HCWs obtained in this study was high while the level of vaccination in this at-risk population was low. Adequate steps should be taken to sensitise this population on HBV and the vaccination procedure.

New Therapeutics for Hepatitis B: The Road to Cure

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Susanna Naggie ◽  
Anna S. Lok
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Human Study ◽  
Current Approach ◽  
Hbv Infection ◽  
Annual Review ◽  
Publication Date ◽  
The Road ◽  
Chronic Hepatitis B Virus ◽  
Current Therapies

Chronic hepatitis B virus (HBV) infection impacts an estimated 257–291 million people globally. The current approach to treatment for chronic HBV infection is complex, reflecting a risk:benefit approach driven by the lack of an effective curative regimen. This complexity and the lack of a durable treatment response, necessitating indefinite treatment in the majority of cases, have resulted in low uptake of testing and treatment, particularly in regions where comprehensive primary care is lacking and access to affordable testing and treatment is limited. Multiple targeted therapies are now in early human study with the primary goal to achieve persistent HBV DNA and hepatitis B surface antigen suppression after a finite course of treatment, which is referred to as functional cure. This article summarizes the current therapies for HBV infection and discusses the limitations of these therapies, novel approaches to HBV cure, and therapeutic endpoints of clinical trials aimed to cure hepatitis B. Expected final online publication date for the Annual Review of Medicine, Volume 72 is January 27, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A hepatitis B- és D-vírus-fertőzés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-től

2018 ◽  
Vol 159 (Supplement 1) ◽  
pp. 24-37
Author(s):  
Gábor Horváth ◽  
Zsuzsanna Gerlei ◽  
Judit Gervain ◽  
Gabriella Lengyel ◽  
Mihály Makara ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Transient Elastography ◽  
Hepatitis B Surface Antigen ◽  
Cost Effective ◽  
Pegylated Interferon ◽  
Hbv Infection ◽  
Hepatitis D ◽  
Cost Effective Approach ◽  
Prolong Life Expectancy ◽  
First Choice

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5–0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24–37.

How Far we are towards Eradication of HBV Infection

2015 ◽  
Vol 24 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Mihai Voiculescu
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Major Health Problem ◽  
Cell Receptors ◽  
B Virus

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity.Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation.It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered. Abbreviations: ALT: alanine aminotransferase; APC: antigen presenting cells; cccDNA: covalently closed circular DNA; HBIG: hepatitis B immunoglobulin; HbsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CTL: cytotoxic T lymphocyte; IFN: interferon; NUC: nucleos(t)ide analogues; pg RNA: pre genomic RNA; TLR: toll-like receptors; TOL: T cell receptors.

scholarly journals 1066. Immune Escape Mutant Detection Using Commercially Available Methods for Hepatitis B Surface Antigen Serological Testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S562-S562
Author(s):  
Robert Gish ◽  
Vincent Streva
Keyword(s):  
Hepatitis B ◽  
Immune Escape ◽  
Hepatitis B Surface Antigen ◽  
Panel Member ◽  
The United States ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Review Panel ◽  
B Virus ◽  
Escape Mutants

Abstract Background Although overall infection rates of Hepatitis B virus (HBV) in the United States (US) remain stable, as many as 2.2 million persons are still chronically infected with Hepatitis B Virus (HBV)1. Persons who inject drugs (PWID) are at a higher risk of HBV infection and since 2009 three states (KY, TN, WV) have reported up to a 114% increase in cases of acute HBV infection due to higher infection rates among a non-Hispanic white populations (30–39 years), and injection drug users2. Hepatitis B vaccination is recommended as primary prevention for adults who are at increased risk for HBV infection, including PWID. However, data from the National Health Interview Survey indicate that hepatitis B vaccination coverage is low among adults in the general population3, and it is likely to be lower among injection drug users. Hepatitis B Surface Antigen (HBsAg) is the first serological marker to appear after HBV exposure and infection; this marker is included in the recommended panel for acute hepatitis diagnosis and accurate detection is necessary for early and accurate diagnosis. Serological testing challenges exist for HBsAg due to the high degree of genetic variability which can further be exacerbated by endogenous and exogenous pressures. The immuno-dominant region may have one or more mutations described as immune escape mutations which can decrease or abrogate HBsAg binding to antibodies used in immunoassays. Although the prevalence of these mutations is not well documented in the United States, international studies have shown that up to 79% of HBV-reactivated patients (vs 3.1% of control patients; p< 0.001) carry HBsAg mutations localized in immune-active HBsAg regions4. Methods A study was conducted using a panel of 10 unique recombinant HBsAg immune escape mutants. Panel members were tested by commercially available HBsAg serological immunoassays. Results It was found that although commercially available HBsAg immunoassays are the primary diagnostic tool for HBV diagnosis, not all HBsAg immune escape mutants are detected, with some method detecting as few as 5 out of 10 of these mutant samples. Figure 1 Conclusion Improvement is needed in commercially available methods for the accurate detection of HBsAg. Disclosures Robert Gish, MD, Abbott (Consultant)AbbVie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Access Biologicals (Consultant)Antios (Consultant)Arrowhead (Consultant)Bayer (Consultant, Speaker’s Bureau)Bristol Myers (Consultant, Speaker’s Bureau)Dova (Consultant, Speaker’s Bureau)Dynavax (Consultant)Eiger (Consultant, Advisor or Review Panel member)Eisai (Consultant, Speaker’s Bureau)Enyo (Consultant)eStudySite (Consultant, Advisor or Review Panel member)Exelixis (Consultant)Fujifilm/Wako (Consultant)Genentech (Consultant)Genlantis (Consultant)Gilead (Consultant, Advisor or Review Panel member, Speaker’s Bureau)GLG (Consultant)HepaTX (Consultant, Advisor or Review Panel member)HepQuant (Consultant, Advisor or Review Panel member)Intercept (Consultant, Speaker’s Bureau)Ionis (Consultant)Janssen (Consultant)Laboratory for Advanced Medicine (Consultant)Lilly (Consultant)Merck (Consultant)Salix (Consultant, Speaker’s Bureau)Shionogi (Consultant, Speaker’s Bureau)Viking (Consultant)

scholarly journals Hepatitis D virus in 2021: virology, immunology and new treatment approaches for a difficult-to-treat disease

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323888
Author(s):  
Stephan Urban ◽  
Christoph Neumann-Haefelin ◽  
Pietro Lampertico
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Treatment Strategies ◽  
Phase Iii ◽  
Interferon Α ◽  
T Cell Epitopes ◽  
The European Union ◽  
Hepatitis D ◽  
Hepatitis D Virus

Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5–10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.

scholarly journals Na+-Taurocholate Co-Transporting Polypeptide (NTCP) in Livers, Function, Expression Regulation, and Potential in Hepatitis B Treatment

Livers ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 236-249
Author(s):  
Xiaoyu Zhao ◽  
Waqas Iqbal ◽  
Pingnan Sun ◽  
Xiaoling Zhou
Keyword(s):  
Hepatitis B ◽  
Hepatoma Cell ◽  
Sodium Taurocholate ◽  
Hbv Infection ◽  
Viral Receptor ◽  
Hepatitis D ◽  
Hepatoma Cell Lines ◽  
Chronic Hepatitis B Virus ◽  
Hepatitis B Treatment

Chronic hepatitis B virus (HBV) infection has become one of the leading causes of liver cirrhosis and hepatocellular carcinoma globally. The discovery of sodium taurocholate co-transporting polypeptide (NTCP), a solute carrier, as a key receptor for HBV and hepatitis D virus (HDV) has opened new avenues for HBV treatment. Additionally, it has led researchers to generate hepatoma cell lines (including HepG2-NTCP and Huh-7-NTCP) susceptible to HBV infection in vitro, hence, paving the way to develop and efficiently screen new and novel anti-HBV drugs. This review summarizes the history, function and critical findings regarding NTCP as a viral receptor for HBV/HDV, and it also discusses recently developed drugs targeting NTCP.

scholarly journals Rituximab increases the risk of hepatitis B virus reactivation in non-Hodgkin lymphoma patients who are hepatitis B surface antigen-positive or have resolved hepatitis B virus infection in a real-world setting: a retrospective study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7481 ◽  
Author(s):  
Yu-Fen Tsai ◽  
Ching-I Yang ◽  
Jeng-Shiun Du ◽  
Ming-Hui Lin ◽  
Shih-Hao Tang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hodgkin Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Non Hodgkin Lymphoma ◽  
B Virus ◽  
Hepatitis Flare

Background Hepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation. Materials Non-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively. Results A total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients’ overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival. Conclusion The incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.

scholarly journals Age-wise and Gender-wise Prevalence of Hepatitis B Virus (HBV) Infection in Lahore, Pakistan

2019 ◽  
Vol 01 (04) ◽  
pp. 20-28
Author(s):  
Aqib Nazeer ◽  
Shahid Ali ◽  
Imran Tipu
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Age Group ◽  
Pakistani Population ◽  
Blood Samples ◽  
Significant Difference ◽  
B Virus ◽  
And Gender

Background The prevalence of hepatitis B virus (HBV) in the Pakistani population has been reported previously, however, studies with a city-oriented approach and focus on age and gender distribution are very limited. Therefore, the current study was designed to unravel the age-wise and gender wise prevalence of HBV in Lahore, Pakistan. Methods A total of 350 blood samples of both male and female patients who visited National Genetic Laboratory, Lahore between February 2019 and July 2019 and who were suspected of HBV infection were screened. Sandwich based ELISA was used to detect rapid hepatitis B surface antigen (HbsAg) according to the manufacturer’s instruction. Real time PCR was used to detect HBV using HBV Rotor Gene PCR kit. Results Out of 350 blood samples screened for HBV infection (n= 350), 180 (51.43%) were of males and 170 (48.57%) were of females. Mean age (years) with SD (standard deviation) of the screened population was 37.22 ± 12.16 years. Overall, 224 samples (64%) were found to be positive for HBV infection. In our study, the number of females with this infection (52.24%) was slightly higher than males (47.76%). However, we observed no statistically significant difference (p = 0.225) between them. Conclusion Our study concludes that HBV is highly prevalent in Lahore, Pakistan. Females are slightly more susceptible to HBV infection as compared to males. This study also reports that HBV is more prevalent in the 20-40 age group.

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