Occult Hepatitis B Virus Infection Research Articles

The Incidence and the Clinical Significance of the Gray Zone in the Clinical Phases of Chronic Hepatitis B Virus Infection

Background: five clinical phases were described in patients with chronic (HBV) infection: HBeAg- positive HBV infection, HBeAg- positive CHB, HBeAg negative HBV infection, HBeAg-negative CHB and occult HBV infection.
 Aim: This study aimed to determine the incidence of the unclassified phase (gray zone) in chronic hepatitis B patients and its significant in the clinical practice. 
 Patients and methods: The study was conducted retrospectively on 109 patients' who have HBsAg positive for more than 6 months. The data recorded include; HbeAg and anti-HBe Ab, ultrasound of the abdomen, HBV DNA load and alanine aminotransferase (ALT), accordingly; we classify the patients to known clinical phases. Patients who were unfit one of these phases considered to be in the gray zone and subsequently sent for liver fibroscan to determine the fibrosis stage. 
 Results: The mean age of our patients was 34.25 (±13.9) years with 54.12% being males. The mean viral load was 5,885,490 IU/ml and mean ALT was 56.22 (±89.88) U/L. eight patients (7.3%) were in the HBeAg+ve HBV infection, 13 patients (11.9%) were in HBeAg+ve CHB . Thirty four patients (31.1%) were in the HBeAg-ve HBV infection and 23 (21.1%) were in HBeAg-ve CHB phase, both were showed a significant statistical relationship with age> 35 years. Thirty one (28.4%) further patients failed to identify with any of the four phases (normal ALT with HBV load > 2000 IU/ml), this group also showed significant relation to age above 35 years and 12 patients (38.8%) had significant fibrosis on fibroscan.
 Conclusions: A considerable number of patients with chronic HBV infection have persistently normal ALT levels, despite elevated levels of viral load; this is known as the "grey zone" phase. These patients merit close follow up with short-interval measurement of liver enzymes, liver fibroscan and biopsy may be considered.

Naturally occurring pre-S mutations promote occult HBV infection by affecting pre-S2/S promoter activity

Occult hepatitis B virus (HBV) infection (OBI) has non-negligible clinical significance, but the mechanism of its occurrence remains unclear. Growing evidence suggests that mutations in the pre-S region of HBV genome may be associated with the occurrence of OBI. However, the role of pre-S mutations in OBI and its molecular mechanism was not fully understand. Here, the pre-S sequences from 307 OBI blood donors and 293 hepatitis B surface protein (HBsAg)-positive blood donors were obtained, and we observed a higher frequency of naturally occurring pre-S mutations in OBI donors infected with genotype B/C HBV than in HBsAg-positive donors, suggesting their potential positive role in OBI. In both genotype B and C, several pre-S mutants resulted in markedly reduced HBsAg production in vitro. In particular, the T68I, S78N and N98T mutants of genotype B were proven to significantly decrease the HBsAg synthesis by affecting the pre-S2/S promoter activity, and thereby promoting the occurrence of OBI.

Prevalence of hepatitis B virus and immunity status among healthcare workers in Beira City, Mozambique.

BackgroundHepatitis B virus (HBV) infection can be prevented by vaccination. Exposure to blood or body fluids poses a high risk of transmission of HBV in health care workers (HCWs). This study aimed to determine the prevalence of markers of exposure, susceptibility, and protection to HBV infection in HCWs in Beira, Mozambique.MethodsA cross-sectional study was conducted between June and August 2020 in Beira City, Mozambique, in HCWs based on self-administered questionnaires and blood samples. Plasma samples were tested for HBV surface antigen (HBsAg), antibodies to HBV core antigen (anti-HBc), antibodies to HBsAg (anti-HBs) and HBV viral load (HBV DNA).ResultsMost of the 315 HCWs in the study were nurses (125; 39.7%). Of the HCWs, 5.1% (16; 95% Confidence Interval (CI): 2.9 to 8.1%) were infected by HBV (HBsAg and/or HBV DNA positive). Occult HBV infection (OBI) (HBV DNA positive and HBsAg negative) was found in 0.3% (1; 95% CI: 0.0 to 1.8%) of participants; 27.9% (88; 95% CI: 23.1 to 33.2%) were susceptible (negative for all markers), 6.3% (20; 95% CI: 3.9 to 9.6) were immune due to natural infection (anti-HBs and anti-HBc positive only), while 60% (189; 95% CI: 54.4 to 65.5) were immune due to vaccination (anti-HBs positive only).ConclusionThis study showed a high intermediate prevalence of chronic hepatitis B among healthcare workers in Beira City, Central Mozambique, and one-third of healthcare workers were susceptible to HBV infection. There is a need to implement a national hepatitis B screening and vaccination strategy among healthcare workers in Mozambique.

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies: Pathogenesis, screening, prevention and treatment.

With a 5.3% of the global population involved, hepatitis B virus (HBV) is a major public health challenge requiring an urgent response. After a possible acute phase, the natural history of HBV infection can progress in chronicity. Patients with overt or occult HBV infection can undergo HBV reactivation (HBVr) in course of immunosuppressive treatments that, apart from oncological and hem-atological diseases, are also used in rheumatologic, gastrointestinal, neurological and dermatological settings, as well as to treat severe acute respiratory syndrome coronavirus 2 infection. The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition. The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence. The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed. The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status. Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Prevalence of occult hepatitis B virus infection among patients receiving haemodialysis in Sana'a city

Occult hepatitis B virus infection (OBI) is a challenging entity. Due to the increase in invasive procedures, blood transfusions, and difficulties in diagnosing OBI, patients are more likely to acquire OBI. This cross-sectional study was conducted to assess the prevalence of OBI by hepatitis B virus (HBV)-DNA detection, the prevalence of HBV infection by total hepatitis B core antibody (HBcAb) detection, and the potential risk factors for HBV infection in patients receiving haemodialysis regularly. This study included 80 patients receiving haemodialysis regularly, without acute or chronic HBV infection. They were selected from the dialysis units in Sana'a city, Yemen from June 2016 to June 2017. Patients who were positive for hepatitis B surface antigen and hepatitis B surface antibody were excluded from this study. Blood samples were taken prior to each haemodialysis session, and serological markers of HBV were included. HBcAb was measured by enzyme-linked immunosorbent assay, and HBV-DNA was measured by polymerase chain reaction. HBV-DNA was detected in four patients (5%) and HBcAb was detected in 38 patients (47.5%). There was a significant association between HBV-DNA and HBcAb in patients receiving haemodialysis regularly. Patients who test positive for HBcAb should undergo additional HBV-DNA testing to allow accurate HBV screening and prevent infection of other patients.

Liver-Related Mortality in Hepatitis B Virus Core Antibody+/Hepatitis B Virus Surface Antigen- Patients: Occult Hepatitis B Virus, Hepatitis B Virus Reactivation, and Hepatocellular Carcinoma Development.

Although hepatitis B virus surface antigen (HBsAg) serum clearance is an important milestone in the natural history of chronic hepatitis B virus (HBV) infection, HBsAg-negative patients are at risk of liver cancer and liver-related death, especially when progressive fibrosis is present. HBsAg-negative/anti-HBV core antibody-positive patients should be carefully evaluated and managed accordingly for the presence of significant liver fibrosis, other viral coinfections, occult HBV infection, risk of HBV reactivation, and hepatocellular carcinoma. Antiviral prophylaxis should be initiated in isolated anti-HBV core antibody patients receiving high-risk chemotherapy or biologics. Hepatocellular carcinoma surveillance with liver ultrasound and serum alpha-fetoprotein should be considered for patients with risk factors.

Estimates of the prevalence of occult HBV infection in Asia: a systematic review and meta-analysis

Purpose Occult Hepatitis B virus infection (OBI) is of great significance to the transmission of Hepatitis B virus (HBV) and the evolution of the patient’s clinical outcome. We conducted a systematic review and meta-analysis to estimate the prevalence of OBI in Asia. Methods Literature search was conducted in PubMed, Cochrane Library database, Web of Science and Embase with the keywords of ‘Hepatitis B virus’, ‘occult infection’, ‘prevalence’. 70 studies were included in the meta-analysis. Meta-analysis was performed using random-effects models to calculate the pooled prevalence of OBI and 95% confidence interval (CI). The data were analyzed in R 4.1.2. Results The overall prevalence of OBI was 4% (95%CI: 0.03–0.06) in Asia. Subgroup analysis based on geographic region showed a prevalence of 3% (95%CI 0.02–0.06) in East Asia, 9% (95%CI 0.05–0.15) in West Asia, 3% (95%CI 0.01–0.11) in Southern Asia and 9% (95%CI 0.05–0.15) in Southeast Asia. Subgroup analysis demonstrated a prevalence of 1% (95%CI 0.00–0.02) in general population, 5% (95%CI: 0.03–0.08) in high-risk population, 9% (95%CI: 0.03–0.22) in the human immunodeficiency virus (HIV)-infected patient, 18% (95%CI: 0.09–0.32) in the hepatopathy patients. Conclusion Based on the meta-analysis of the prevalence of OBI in different populations, we concluded that the prevalence of OBI in the high-risk population, hepatopathy patients, and HIV-infected patients was higher than that in the general population. A systematic review showed that OBI was associated with disease progression and prognosis. Therefore, these populations should be routinely screened for OBI and promptly intervened to avoid promoting disease progression.

Correlation of serological and molecular markers in the screening for hepatitis B virus in blood bank in northern Brazil

IntroductionIn Brazil, the blood donor screening for hepatitis B virus (HBV) includes laboratory testing for serological (HBsAg and Anti-HBc) and molecular (HBV DNA) markers. This study aims to correlate serology reactive results with HBV DNA detection among blood donors with at least one HBV infection marker detected in a blood bank in northern Brazil. MethodA retrospective search for HBV reactive blood donor data from January 2017 to December 2019 was performed. Serological screening was performed by chemiluminescent microparticle immunoassays Architect HBsAg and Architect Anti-HBc, whereas molecular screening was performed by the HBV nucleic acid test (HBV NAT). Main resultsA total of 556 HBsAg reactive results were detected, between positive (47.66%) and inconclusive (52.34%). A total of 3,658 Anti-HBc reactive results were detected, between positive (83.71%) and inconclusive (16.29%). None of the inconclusive results were associated with HBV DNA detection. The HBV DNA detection rates were 47.55% among HBsAg positive samples and 4.08% among Anti-HBc positive samples. The signal-to-cutoff (S/CO) ratio median of HBV NAT positive samples was superior in comparison to HBV NAT negative samples (p < 0.0001). The thresholds found to optimize sensitivity and specificity were 404.15 for Architect HBsAg and 7.77 for Architect Anti-HBc. Three blood donors were in the window period and 1 occult HBV infection case was detected. ConclusionHigh S/CO ratios were more predictive of HBV DNA detection. However, a number of HBV NAT positive samples gave low values, while some HBV NAT negative samples showed high values, reaffirming the significance of molecular testing to enhance transfusion safety.

Role of S protein transmembrane domain mutations in the development of occult hepatitis B virus infection

ABSTRACT Occult HBV infection (OBI) is a special infection status during Hepatitis B virus (HBV) infection. The underlying mechanism of its occurrence remains unclear. This study conducted sequencing analysis on 104 OBI plasma samples and 524 HBsAg positive samples from 29 blood centres, and searched for high-frequency mutations in transmembrane domain (TMD) of S protein in the OBI population. Plasmids with TMD high-frequency mutations were constructed, in vivo and in vitro functional experiments were performed to investigate possible molecular mechanisms of OBI occurrence. We found 22 high-frequency TMD mutations in genotype B OBI strains. Among them, five mutations can lead to impairment of HBsAg secretion; seven mutations had accumulated intracellular HBsAg while extracellular HBsAg didn’t decrease compared to wildtype. This study chose C85R from TMD2, F220C, and F220Y from TMD4 for further exploration. Protein structure predication showed these three mutant HBsAg displayed changed hydrophilic properties and tended to accumulate in the phospholipid bilayer of cell membrane. Mutant HBsAg’s secretion disorder may induce OBI. On the other hand, V168A + V177A from TMD3 expressed increased HBsAg both in intracellular and extracellular levels. This mutation had most unstable natural conformation and may be inclined to transition into V177A or V168A + S174N + V177A. These three mutations were more prone to mixed infection, presenting a state of coexistence, thus approaching the impaired secretion pattern of OBI. This study demonstrated TMD mutations could contribute to the occurrence of OBI and provided a theoretical basis for OBI study and the functional cure of chronic hepatitis B virus infection.

Meta-analysis: hepatitis B reactivation in patients receiving biological therapy.

The use of biologics poses a moderate to high risk for hepatitis B virus reactivation (HBVr) in chronic carriers. To determine the prevalence of HBVr with TNF alpha inhibitors, ustekinumab and vedolizumab METHOD: We followed the MOOSE guidelines and conducted a comprehensive literature search. We conducted a systematic search of EMBASE (Ovid), MEDLINE (Ovid) and PubMed. The studies included patients who were chronic and occult HBV carriers with various rheumatological, dermatological or gastroenterological conditions. We used a random effects model using pooled estimates (prevalence of HBVr with 95% confidence intervals (CI)). We included 29 studies with 1409 patients infected with HBV. The prevalence of HBVr in chronic carriers of HBV was 17.1% (95% CI: 7.0-35.9, n= 5), 16.6% (95% CI: 9.5-27.5%, n= 6), 40.5% (95% CI: 20.3-64.5%, n= 4) and 19.1% (95% CI: 7.3-41.2%, n= 2), respectively, for adalimumab, etanercept, infliximab and ustekinumab. The respective prevalence for reactivation in patients with occult HBV infection was 5.0% (95% CI: 2.8-8.7%, number of studies: n= 18), 2.6% (95% CI: 1.4-4.7%, n= 18), 4.4% (95% CI: 2.2-8.7%, n= 12) and 6.4% (95% CI: 2.2-16.8, n= 5). There were 39 HBVr (26 in chronic HBV and 13 in the occult group) without any hepatic failure or death. In the chronic HBVr group, only three of 24 patients received antiviral prophylaxis. HBVr prevalence rates differ between the chronic carrier state and the occult carrier state. The uptake of prophylactic antiviral therapy in high-risk groups was low, contrary to clinical practice guidelines.

Control of occult hepatitis B virus infection.

The diagnosis of hepatitis B virus (HBV) infection requires HBV DNA testing and serologic testing for detection of the surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). There is a population of patients with occult HBV infection (OBI), which is not detected by HBsAg or HBV DNA quantification in blood, despite the presence of active replication in the liver. This document provides a definition of OBI and describes the diagnostic techniques currently used. It also addresses the detection of patients with risk factors and the need for screening for OBI in these patients. Correct diagnosis of OBI prevents HBV reactivation and transmission. Diagnosis of OBI is based on the detection of HBV DNA in patients with undetectable HBsAg in blood. A high number of patients with OBI may remain undiagnosed; therefore, screening for OBI in patients with factor risks is essential. For a correct diagnosis of OBI, it is necessary that new markers such as ultrasensitive HBsAg are incorporated, and a more comprehensive marker study is performed by including markers such as cccDNA.

Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis

Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination agenda. We aimed to estimate the prevalence of occult HBV infection at a global and regional scale and in specific populations. For this systematic review and meta-analysis, we searched the MEDLINE, Embase, Global Health, and Web of Science databases for articles published in any language between Jan 1, 2010, and Aug 14, 2019. We included original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults (aged ≥18 years) who are positive for HBV DNA (ie, people with occult HBV infection). The prevalence of occult HBV infection was pooled, using the DerSimonian-Laird random-effects model, in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease), and stratified by HBV endemicity in each country. We also assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection. The study was registered with PROSPERO, CRD42019115490. 305 of 3962 articles were eligible, allowing a meta-analysis of 140 521 993 individuals tested for HBV DNA. Overall, only two studies evaluated occult HBV infection in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence. In blood donors, occult HBV infection prevalence mirrored HBV endemicity: 0·06% (95% CI 0·00-0·26) in low-endemicity countries, 0·12% (0·04-0·23) in intermediate-endemicity countries, and 0·98% (0·44-1·72), in high-endemicity countries (p=0·0012). In high-risk groups, occult HBV infection prevalence was substantial, irrespective of endemicity: 5·5% (95% CI 2·9-8·7) in low-endemicity countries, 5·2% (2·5-8·6) in intermediate-endemicity countries, and 12·0% (3·4-24·7) in high-endemicity countries. The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI 62-88) and its specificity was 76% (68-83). A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries. Occult HBV infection should be part of the global viral hepatitis elimination strategy. None.

Global burden of occult hepatitis B virus infection: where we are and what to do

Occult hepatitis B virus (HBV) infection is characterised by the persistence of replication-competent HBV DNA in the liver (with or without HBV DNA in the blood) of individuals testing negative for HBsAg, using currently available assays.1 Occult HBV infection represents a phase of the natural history of HBV infection,2 in which HBV DNA in the form of a covalently closed circular DNA minichromosome has suppressed replicative activity and gene expression with extremely low rates of virion production.

Residual risk of hepatitis B virus transmission through blood donations in Burkina Faso screened with rapid diagnostic tests.

Background and Aimshepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) represent the major transfusion–transmissible pathogens worldwide. The risk of transmission is relatively high in African countries, mainly due to unreliable screening methods of blood donations. In Burkina Faso, predonation screening using rapid diagnostic tests (RDTs) is widespread, raising the major question of the transfusion safety in the country. The objective of this study was to assess the risk of transmission of HBV, HCV, and HIV through blood transfusion in the context of the use of RDTs for screening of the blood donations.MethodsIn this cross‐sectional study, a total of 417 serum samples obtained from blood donors tested negative for HBsAg, anti‐HCV, and anti‐HIV using RDTs were retested for the same markers using chemiluminescent immunologic assays. Total antibodies to HBV core (anti‐HBc) were tested on randomly selected samples. HBV‐DNA and HCV‐RNA viral loads (VLs) were quantified on HBsAg and anti‐HCV positive samples, respectively. To assess possible occult hepatitis B infection (OBI), HBV‐DNA‐VL was quantified on 313 randomly selected HBsAg‐negative samples.ResultsHBsAg and anti‐HCV were found respectively in 6 (6/417; 1.4%) and 11 (11/417; 2.6%) samples. No samples were reactive for anti‐HIV. Total anti‐HBc were detected in 217 out of the 319 randomly selected samples (217/319; 68.02%). HBV‐DNA was detected in four (4/313; 1.27%) samples, including two (2/6; 33.33%) of the six HBsAg positive samples and two (2/313; 0.6%) of the HBsAg‐negative samples, suggesting two cases of occult HBV infection. All anti‐HCV antibody‐positive samples were HCV‐RNA negative.ConclusionThis study shows that RDTs are not sufficiently sensitive for the screening of blood donations. Our results highlight the urgent need to think about the extension of sensitive immunological tests in all blood transfusion centers and also the implementation of nucleic acid amplification techniques.

Occult hepatitis B virus infection among patients with chronic liver disease of unidentified cause, Addis Ababa Ethiopia

Occult hepatitis B virus infection (OBI) characterized by the absence of detectable HBsAg in the presence of HBV DNA in the serum and/or liver tissue remains a potential risk of transmission and diseases progression among different population groups. It could be associated with asymptomatic case up to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). The objective of this study was to assess the magnitude and characteristics of OBI among patients with CLD of unidentified cause in Addis Ababa, Ethiopia. The study was conducted at the gastroenterology & hepatology referral clinic of three government and two private hospitals in Addis Ababa. Known CLD patients as evidenced by clinical and imaging criteria and/or with HBV surface antigen (HBsAg) negative results using rapid test kit were included. ELISA serological test to anti-HBc Ab, anti HBsAg Ab, and HBsAg were determined using BIORAD kits [https://www.bio-rad.com]. HBV-DNA was amplified, and viral loads were determined by quantitative real-time PCR using Abbott m2000rt platform following the manufacturer's instructions. Data analysis was done using SPSS version 20.A total of 48 CLD patients with no identified cause for their liver disease were identified during the study period. All the patients had evidence of CLD by clinical and imaging criteria and nine were excluded. Three (7.69%) of the 39 patients tested positive for HBsAg test done by ELISA making the negative predictive value of the rapid test kits 92.3% compared to ELISA. The remaining 36 patients had serology test for HBV and 16 (44.4%) had positive anti-HBV core antibody. Two (5.56%) of the 36 patients with HBV viral load determination had detectable HBV DNA suggesting presence of an occult hepatitis B infection. Occult hepatitis B infection is found to be an aetiology among CLD patients labelled as having no identified cause by the current standard of care using rapid HBsAg kits in a subset of patients in Ethiopia. This study signifies the high rate of OBI and past evidence of HBV infection among CLD patients and thus nucleic acid testing and/or anti-HBc shall be integrated to the routine health care system to minimize HBV infection risk of transmission and to enhance patient care.

New design and optimization of an in-house quantitative TaqMan Real-Time PCR-based assay for the detection and monitoring of occult hepatitis B virus (genotype A-J) infection

PurposeHBV DNA quantification is used for individuals with uninterpretable serological tests, occult HBV infections, decreasing the window period of the disease, and treatment follow-up. Although there are commercial qPCR assays, they are expensive. In this study, we developed a highly sensitive quantitative TaqMan Real-Time PCR with an exogenous internal control to quantify HBV DNA in serum/plasma. MethodsA specific primer/probe set was designed for the S conserved region of various HBV genotypes. The primer/probe set was evaluated experimentally and in-silico. An exogenous internal control was included to monitor the effects of inhibitors. The standard plasmid was titrated using three different methods to prepare the seven standards for the assay. The functional characteristics of the in-house assay were evaluated using the standards. Two hundred clinical specimens were also tested. ResultsThe LOD of the in-house assay was 40 IU/mL, and the assay was linear from 3.26Log10 to 9.26Log10 IU/mL. The analytical and clinical sensitivity of the assay was 100% and 92.15%, respectively. The analytical and clinical specificity of the assay was 100% and 98.97%, respectively. The positive and negative predictive values of the assay were determined to be 98.94% and 92.38%, respectively. The highest coefficient of variation of the inter/intra-assay was 5.1%. The accuracy was close to 100% for all standards, and the correlation between the in-house assay and commercial kit AltoStar® PCR Kits 1.5 was remarkable. The results of the clinical samples using the standards titrated using AcroMetrix™ HBV Panel, Artus® HBV RG PCR Kit, and AltoStar® PCR Kits 1.5 were comparable (r ​= ​0.942, 0.951, 0.951). ConclusionsThe results indicate that the in-house assay is highly sensitive and specific, reproducible, and cost-benefit. Thus, it can be used to detect and quantify HBV DNA in research and clinical settings.

Prevalence of hepatitis B virus core antibodies among blood donors in Nigeria: Implications for blood safety.

BackgroundAnti-hepatitis B core antibody (anti-HBc) testing improves transfusion safety by detecting past and current hepatitis B virus (HBV) infection while detecting hepatitis B surface antigen (HBsAg) in serology-negative HBV infection. However, occult HBV infection (OBI) (serum or liver HBV DNA-positive but HBsAg-negative) remains unaddressed among replacement blood donors – family members or friends who donate to replace blood transfused to a relative.ObjectiveThis study assessed risk factors for a positive anti-HBc test among donors with OBI and determined the anti-HBc-positive status of replacement donors.MethodsThe study was conducted at the University College Hospital Blood Bank, Ibadan, Nigeria, using blood samples collected from blood donors between April 2019 and May 2019. Donors were screened for HBsAg by rapid diagnostic test (RDT) and enzyme-linked immunosorbent assay (ELISA) and anti-HBc by ELISA, while HBV DNA was detected using a semi-nested polymerase chain reaction.ResultsOf the 274 participants, 15 (5.5%) were HBsAg-positive by RDT and 36 (13.1%) by ELISA, while 133 (48.5%) were anti-HBc positive. Out of 232 HBsAg-negative donors, 107 (46.1%) were anti-HBc positive. Of the 107 HBsAg-negative but anti-HBc-positive samples, only one (0.93%) was HBV DNA-positive. The HBV DNA-positive donor was HBsAg-negative by both RDT and ELISA tests.ConclusionThis study establishes a potential risk for HBV transmission from isolated anti-HBc-positive donors to blood recipients. HBc immunoglobulin (antibody) M testing to identify blood units requiring further screening with polymerase chain reaction to detect OBI can prevent HBV transmission through blood transfusion.

Occult hepatitis B virus infections and risk factors among school-going adolescent voluntary blood donors in Kwale County Kenya, January 2020-June 2021: Cross sectional study.

Occult hepatitis B virus (HBV) infections remain a safety concern worldwide. The prevalence in Kenya ranges from 2.6% to 4.4% among secondary school-going voluntary blood donors. This study estimated the prevalence of occult HBV infections among school-going voluntary blood donors through donations made to Kwale Satellite Blood Transfusion Center (KSBTC). This was a retrospective cross-sectional study on data collected by the KSBTC between January 2020 and June 2021 among secondary school-going voluntary blood donors. Data were collected in MS Excel 2013 and analyzed in Epi Info 7. Descriptive statistics were calculated and we compared donors with positive Hepatitis B surface antigen (HBsAg) to those with negative HBsAg. Crude Prevalence Odds Ratios (cPOR) at 95% confidence intervals (CI) were calculated to identify factors associated with positive HBsAg. A total of 613 records were analyzed. The mean age of the donors was 19.1 years (± 1.8 years), there were 457 males (74.5%), 502 individuals were in the age group 18-25 years (82.3%), and the mean hemoglobin level was 14.1 g/dl (±1.6 g/dl). First-time blood donors made up 84.8% of all donors (513/605) and the mean inter-donation period was 20 months (±5.8 months) for repeat donors. The sero-positivity for HBsAg was 8.8% (54/613). Age category 16-17 years with positive HBsAg were 10.2% (11/108), femaleswere10.9% (17/156), and first-time donors were 9.4% (48/513). On bivariate analyses, first-time blood donors were 1.5 times more likely to test positive for HBsAg compared to repeat donors (cPOR = 1.5, 95% CI 0.61-3.57). Females were 1.4 times more likely to test positive for HBsAg compared to male donors (cPOR = 1.4, 95% CI 0.76-2.54). The majority of the voluntary blood donors were males and the majority of occult HBV infections came in the first-time blood donor group. We recommend increasing targeted recruitment of repeat donors by encouraging healthy first-timer donors to be regular donors, and suggest this population should be vaccinated against HBV infections.

The Investigation of HBV Pre-S/S Gene Mutations in Occult HBV Infected Blood Donors with anti-HBs Positive.

Introduction The coexistence of hepatitis B virus (HBV) and hepatitis B surface antibodies (anti-HBs) in occult hepatitis B virus infection (OBI) is a contradictory phenomenon, and the underlying mechanism is not fully understood. The characteristics of pre-S/S mutations in OBI genotypes B and C (OBIB and OBIC) in the presence or absence of anti-HBs were analyzed extensively in this study. Methodology. The amino acid substitutions of envelope proteins of 21 OBI strains, including 4 HBs (+) OBIB, 6 HBs (−) OBIB, 6 HBs (+) OBIc, and 5 HBs (−) OBIC samples, were analyzed and fully compared among groups of HBV genotypes and the presence of anti-HBs. Results The mutation rates in pre-S1, pre-S2, and S proteins of OBIC were significantly higher than wild-type HBV (wt-HBV) genotype C strains, but only the mutation rate of S protein in OBIB was significantly higher compared to wild-type HBV genotype B. The mutation rates in S protein of anti-HBs (−) OBI were higher than anti-HBs(+) OBI samples (4.40% vs. 2.43% in genotype B, P > 0.05; 6.81% vs. 3.47% in genotype C, P < 0.05). For these high-frequency substitutions in the pre-S/S region, the mutations sN40S and sK122R were found in 27.3% and 45.5% of anti-HBs (−) OBI strains, respectively. 7 substitutions were uniquely found in OBIC strains and 9 substitutions were commonly detected in OBIB and OBIC strains. Conclusions These results suggested that the mutations might occur randomly and were not selected by antibody pressure.

Occult Hepatitis B Virus Infection Among Blood Donors in the Capital City of Addis Ababa, Ethiopia: Implications for Blood Transfusion Safety

BackgroundOccult hepatitis B virus infection (OBI) remains a potential threat to blood safety in developing countries. Nevertheless, there is no data available on the magnitude of occult hepatitis among blood donors in Ethiopia. Therefore, this study aimed to estimate the magnitude of OBI among blood donors in Ethiopia.ObjectivesThe aim of this study is to determine the magnitude of OBI and associated risk factors among blood donors at the National Blood Bank, Addis Ababa, Ethiopia.MethodsA total of 973 HBsAg-negative plasma samples were tested for anti-HBc antibody using an ELISA and viral DNA using automated ABBOTT real-time PCR. Along with plasma samples, demographic data were retrieved from the database with respect to donors. Both descriptive and inferential statistics were employed for the analysis of data by SPSS 20. p-values less than 0.05 were considered as statistically significant.ResultsOf the total of 973 study participants, 445 (45.7%) were female with a mean age of 26.5 years. A total of 144 (14.8%) blood samples were anti-HBc antibody reactive. Four (0.41% of all samples, and 2.8% of anti-HBc-positive samples) samples were confirmed to have OBI by DNA detection. The mean viral load among the confirmed OBI samples was 31 IU/ml with ±12 SD, suggesting true occult hepatitis BV infections. Age was found to be a risk factor for anti-core positivity and was statically significant at p = 0.0001.ConclusionAbout four out of 1,000 blood donors screened negative with HBsAg had occult HBV infection. This shows that there could be a risk of HBV transmission through blood transfusion in Ethiopia. Therefore, there is a need for further investigation and action to revise the existing blood screening strategy by including anti-HBc and HBV nucleic acid testing.