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

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)

2018 ◽  
Vol 36 (10) ◽  
pp. 959-967 ◽  
Author(s):  
Jessica P. Hwang ◽  
Anna S. Lok ◽  
Michael J. Fisch ◽  
Scott B. Cantor ◽  
Andrea Barbo ◽  
...  

Purpose Most patients with cancer are not screened for hepatitis B virus (HBV) infection before undergoing anticancer therapy, and optimal screening strategies are unknown. We sought to develop selective HBV screening strategies for patients who require systemic anticancer therapy. Methods This prospective cohort study included adults age ≥ 18 years with solid or hematologic malignancies who received systemic anticancer therapy at a comprehensive cancer center during 2013 and 2014. Patients underwent hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody testing, and completed a 19-question modified Centers for Disease Control and Prevention (CDC) HBV survey. Multivariable models that predict chronic or past HBV infection were developed and validated using bootstrapping. Results A total of 2,124 patients (mean age, 58 ± 13 years) completed the risk survey and HBV testing. Of these, 54% were women; 77% were non-Hispanic white, 11% Hispanic, 8% black, and 4% Asian; and 20% had a hematologic malignancy and 80% a solid tumor. Almost 12% were born outside the United States. The prevalence was 0.3% for chronic HBV infection and 6% for past HBV infection. Significant predictors of positive hepatitis B surface antigen or hepatitis B core antibody tests were as follows: men who had sex with men, black or Asian race, birthplace outside the United States, parent’s birthplace outside the United States, household exposure to HBV, age ≥ 50 years, and history of injection drug use. The area under the receiver operating characteristic curve of the model on the basis of these seven predictors was 0.79 (95% CI, 0.73 to 0.82). The modified CDC survey and brief tools with fewer than seven questions yielded similar false-negative rates (0% and 0% to 0.7%, respectively). Conclusion An internally validated risk tool performed as well as the modified CDC survey; however, more than 90% of patients who completed the tool would still require HBV testing. Universal HBV testing is more efficient than risk-based screening.


2015 ◽  
Vol 24 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Mihai Voiculescu

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.


2018 ◽  
Vol 41 (4) ◽  
pp. 765-771 ◽  
Author(s):  
E N Kisangau ◽  
A Awour ◽  
B Juma ◽  
D Odhiambo ◽  
T Muasya ◽  
...  

Abstract Background Hepatitis B virus (HBV) is a vaccine-preventable infection that can spread in healthcare setting. Data on HBV infections and vaccine in African healthcare workers (HCWs) are limited. We estimated HBV infection prevalence, hepatitis B vaccination status and identified factors associated with vaccination in one Kenyan county. Methods Randomly selected HCWs completed a questionnaire about HBV exposure and self-reported immunization histories, and provided blood for testing of selected HBV biomarkers to assess HBV infection and vaccination status: HBV core antibodies (anti-HBc), HBV surface antigen (HBsAg) and HBV surface antibodies (anti-HBs). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated to identify factors associated with vaccination. Results Among 312 HCWs surveyed, median age was 31 years (range: 19–67 years). Of 295 blood samples tested, 13 (4%) were anti-HBc and HBsAg-positive evidencing chronic HBV infection; 139 (47%) had protective anti-HBs levels. Although 249 (80%) HCWs received ≥1 HBV vaccine dose, only 119 (48%) received all three recommended doses. Complete vaccination was more likely among those working in hospitals compared to those working in primary healthcare facilities (OR = 2.5; 95% CI: 1.4–4.3). Conclusion We recommend strengthening county HCW vaccination, and collecting similar data nationally to guide HBV prevention and control.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7481 ◽  
Author(s):  
Yu-Fen Tsai ◽  
Ching-I Yang ◽  
Jeng-Shiun Du ◽  
Ming-Hui Lin ◽  
Shih-Hao Tang ◽  
...  

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.


2017 ◽  
Vol 11 (4) ◽  
Author(s):  
S. Rolland ◽  
L. Antonova ◽  
J. Powis ◽  
T. Murdoch ◽  
D. Wong ◽  
...  

Clinicians often assume that patients vaccinated for hepatitis B virus (HBV) have immunity. We report three cases of acute HBV infection in HBV-vaccinated HIV patients. These cases illustrate that patients at an elevated risk of HBV exposure presenting with acute hepatitis should be tested for HBV infection regardless of previous vaccination status.


2019 ◽  
Vol 01 (04) ◽  
pp. 20-28
Author(s):  
Aqib Nazeer ◽  
Shahid Ali ◽  
Imran Tipu

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.


2020 ◽  
Vol 33 (2) ◽  
Author(s):  
Mindie H. Nguyen ◽  
Grace Wong ◽  
Edward Gane ◽  
Jia-Horng Kao ◽  
Geoffrey Dusheiko

SUMMARY Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV’s epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Gideon K. Helegbe ◽  
Faiza Tanko ◽  
Paul A. Aryee ◽  
Setor Aku Lotsu ◽  
Mathias J. A. Asaarik ◽  
...  

The Bolgatanga Municipal Health Directorate has reported liver cirrhosis among the first three diseases causing mortality from 2013 to 2015. This implicates hepatitis B virus (HBV) infection considering its high prevalence among blood donors in the Upper East Region of Ghana. However, for a vulnerable group such as market women, there is not much information with regard to the prevalence, knowledge, and attitude towards HBV infection. Thus, this study sought to bridge this gap by determining the seroprevalence, knowledge, and attitude of market women in the Bolgatanga Municipality of Ghana, towards HBV infection. A cross-sectional descriptive study was conducted (from October 2017 to March 2018) among 404 market women using a pretested questionnaire to ascertain the knowledge and attitudes of market women towards HBV infection, while hepatitis B surface Antigen Rapid Diagnostic Test strips were used to screen for the infection. The study revealed that the seroprevalence of hepatitis B among the market women was 15.6%, and majority of the study subjects (>60%) were unaware of HBV infection. Overall, knowledge on and attitude towards HBV infection were low and poor, respectively, with a significantly high number of the market women not wanting infected individuals to be isolated (p=0.049). A high seroprevalence, together with poor attitude and low knowledge levels, as seen in this study is of great public health concern. The study recommends regular HBV screening for market women for prompt treatment and vaccination as well as continuous health education to increase knowledge level and improve the poor attitudes of market women towards HBV infection.


Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2419-2425 ◽  
Author(s):  
Jean-Pierre Allain ◽  
Daniel Candotti ◽  
Kate Soldan ◽  
Francis Sarkodie ◽  
Bruce Phelps ◽  
...  

The risk of hepatitis B virus (HBV) transmission by transfusion in sub-Saharan Africa is considered to be relatively low, and testing of blood donors is often not done or is done relatively poorly. To re-examine this attitude, we identified HBV chronically infected blood donors from a major hospital in Ghana with a range of hepatitis B surface antigen (HBsAg) assays. Test efficacy was estimated using HBV DNA as a gold standard, and the risk of HBV infection in blood recipients was estimated for different testing strategies. Particle agglutination, dipstick, and enzyme immunoassay (EIA) HBsAg screening detected 54%, 71%, and 97% of HBV infectious donors, respectively. The risk of HBV transmission to recipients less than 10 years old ranged between 1:11 and 1:326 with blood unscreened and screened by EIA, respectively. For older recipients, the risk decreased a further 4-fold because of the high frequency of natural exposure to HBV. A total of 98% of HBsAg-confirmed positive samples contained HBV DNA. HBV DNA load was less than 1 × 104 IU/mL in 75% of HBsAg-reactive samples, most of them anti-HBe reactive. Approximately 0.5% of HBsAg-negative but anti-HBc-positive samples contained HBV DNA. The use of sensitive HBsAg tests is critical to prevent transfusion transmission of HBV infection to young children in a population with a 15% prevalence of chronic HBV infection in blood donors. However, this will not have much effect on the prevalence of this infection unless other strategies to protect children from infection are also advanced in parallel.


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