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Background: The pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI. Methods: This research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals. Mass spectrometry-based detection was used to analyze the proteome, while nuclear magnetic resonance spectroscopy was employed to study the metabolomic phenotypes. Differential molecule analysis, pathway enrichment and functional annotation, as well as weighted correlation network analysis (WGCNA), were conducted to uncover the characteristics of HBV-related liver disease. Prognostic biomarkers were identified using machine learning algorithms, and their validity was confirmed in a larger cohort using enzyme linked immunosorbent assay (ELISA). Results: HBsAg-positive HBV individuals showed higher ALT levels (p =0.010) when compared to OBI patients. The influence of HBV infection on metabolic functions and inflammation was evident through the analysis of distinct metabolic pathways in HBsAg-positive HBV and OBI groups. Tissue tracing demonstrated a connection between Kupffer cells and HBsAg-positive HBV infection, as well as between hepatocytes and OBI. Immune profiling revealed the correlation between CD4 Tem cells, memory B cells and OBI, enabling a rapid response to infection reactivation through cytokine secretion and antibody production. A machine learning-constructed and significantly expressed molecule-based diagnostic model effectively differentiated HBsAg-positive and OBI groups (AUC values > 0.8). ELISA assay confirmed the elevation of FGB and FGG in OBI samples, suggesting their potential as biomarkers for distinguishing OBI from HBsAg-positive infection. Conclusions: The immune microenvironment and metabolic status of HBsAg-positive HBV patients and OBI patients vary significantly. The machine learning-based diagnostic model described herein displayed impressive classification accuracy, presenting a non-invasive means of differentiating between OBI and HBsAg-positive HBV infections. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real‐world setting. Design: Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV‐monoinfected; (b) HIV‐positive/HBcAb‐positive/HBsAg‐negative; (c) HIV‐positive/HBsAg‐positive. The occurrence of VR, defined as two consecutive HIV‐RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. Methods: Standard survival analysis by means of Kaplan–Meier curves and Cox regression analysis with the serology exposure fitted as a time‐fixed covariate measured at baseline was employed after controlling for key confounding factors. Results: Of a total of 5657 patients included, 4090 (72%) were HIV‐monoinfected, 1342 (23.7%)were HBcAb‐positive, and 225 (3.9%) were HbsAg‐positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow‐up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV‐monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg‐positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03–2.38, p = 0.037] but an excess of risk was also seen in those who were HIV‐positive/HBcAb‐positive/HBsAg‐negative (aHR = 1.25, 95% CI: 1.00–1.55, p = 0.047). Conclusions: Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV‐monoinfected and their HIV‐RNA should be carefully monitored. [ABSTRACT FROM AUTHOR]

Background: Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic. Methods: MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model. Results: Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P < 0.05). Furthermore, the predicted transfusion-transmitted HBV cases prevented was 1.25 times more by ID NAT compared to MP-6 NAT. The cost-benefit ratio of the universal HBsAg screening, HBsAg plus ID NAT and HBsAg plus MP NAT were 1:58, 1:27 and 1:22, respectively. Conclusions: Universal HBsAg ELISA screening in combination with HBV ID NAT or MP-6 NAT strategies was highly cost effective in China. To further improve blood safety, HBsAg plus HBV DNA ID NAT screening should be considered in HBV endemic regions/countries. [ABSTRACT FROM AUTHOR]

BackgroundThe pathological and physiological characteristics between HBsAg-positive HBV infection and occult hepatitis B infection (OBI) are currently unclear. This study aimed to explore the immune microenvironment in the peripheral circulation of OBI patients through integration of proteomic and metabolomic sequencing, and to identify molecular biomarkers for clinical diagnosis of HBsAg-positive HBV and OBI.MethodsThis research involved collection of plasma from 20 patients with OBI (negative for HBsAg but positive for HBV DNA, with HBV DNA levels < 200 IU/mL), 20 patients with HBsAg-positive HBV infection, and 10 healthy individuals. Mass spectrometry-based detection was used to analyze the proteome, while nuclear magnetic resonance spectroscopy was employed to study the metabolomic phenotypes. Differential molecule analysis, pathway enrichment and functional annotation, as well as weighted correlation network analysis (WGCNA), were conducted to uncover the characteristics of HBV-related liver disease. Prognostic biomarkers were identified using machine learning algorithms, and their validity was confirmed in a larger cohort using enzyme linked immunosorbent assay (ELISA).ResultsHBsAg-positive HBV individuals showed higher ALT levels (p=0.010) when compared to OBI patients. The influence of HBV infection on metabolic functions and inflammation was evident through the analysis of distinct metabolic pathways in HBsAg-positive HBV and OBI groups. Tissue tracing demonstrated a connection between Kupffer cells and HBsAg-positive HBV infection, as well as between hepatocytes and OBI. Immune profiling revealed the correlation between CD4 Tem cells, memory B cells and OBI, enabling a rapid response to infection reactivation through cytokine secretion and antibody production. A machine learning-constructed and significantly expressed molecule-based diagnostic model effectively differentiated HBsAg-positive and OBI groups (AUC values > 0.8). ELISA assay confirmed the elevation of FGB and FGG in OBI samples, suggesting their potential as biomarkers for distinguishing OBI from HBsAg-positive infection.ConclusionsThe immune microenvironment and metabolic status of HBsAg-positive HBV patients and OBI patients vary significantly. The machine learning-based diagnostic model described herein displayed impressive classification accuracy, presenting a non-invasive means of differentiating between OBI and HBsAg-positive HBV infections.

Background: Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in individuals who test negative for hepatitis B surface antigen (HBsAg). It poses diagnostic challenges and contributes to chronic liver diseases. Understanding its epidemiology, pathogenesis and clinical outcomes remains essential. This study aimed to assess the prevalence and characteristics of OBI in Northwestern Greece. Methods: Serum samples were prospectively collected from 702 blood donors at the University Hospital of Ioannina, Greece, between February 2018 and September 2022. The investigation focused on the presence of hepatitis B virus (HBV) markers, utilizing the Abbott Architect HBsAg and HBcAb HB Qualitative II kit for the detection of HBsAg and anti-HBc, respectively. Further analysis was conducted on serum samples from individuals who tested negative for HBsAg but positive for anti-HBc, employing polymerase chain reaction (PCR) to detect HBV-DNA. In instances of OBI, sequencing and mutation analysis of the HBV pre-S/S gene were carried out for comprehensive characterization. Results: Screening revealed 56 cases (7.9%) with active HBV infection (HBsAg positive) and identified 144 cases (20.5%) indicative of past HBV infection (HBsAg negative, anti-HBc positive). Additionally, a prevalence of 5.4% (38/702) of OBI was detected. Among these, 36 cases exhibited a low HBV DNA load of less than 225 IU/mL. Notably, one OBI patient was co-infected with HIV. Furthermore, two cases of OBI with high HBV-DNA levels exceeding 200,000 IU/ml were detected. Sequencing analysis unveiled S- and pre-S mutations in four cases of OBI, including both instances with elevated HBV-DNA levels. Conclusion: In a region with a high proportion of immigrants from countries where HBV is endemic, a high prevalence of HBV infection and occult HBV infection (OBI) has been detected. Furthermore, mutations in the S gene were found to be associated with cases of OBI with high levels of HBV-DNA. However, additional research is needed to validate the results and understand the clinical relevance of specific OBI mutations for disease progression and treatment efficacy. [ABSTRACT FROM AUTHOR]

The aim of the work is to assess the prevalence of hepatitis B virus drug resistance mutations and immune escape mutations in pregnant women in the Republic of Guinea. Materials and methods. Blood plasma samples obtained from 480 pregnant women from different regions of the Republic of Guinea with laboratory-confirmed viral hepatitis B were studied. Nucleotide sequences for genotype identification and mutation detection were obtained using nested-PCR followed by Sanger sequencing, based on overlapping pairs of primers spanning the complete genome of the virus. Results and discussion. In the examined group, the viral genotype E was the most prevalent (92.92%) compared with subgenotypes A1 (1.67%), A3 (1.46%), D1 (0.63%), D2 (1.04%) and D3 (2.29%). Among the examined HBV-infected pregnant women, 188 (39.17%) had undetectable HBsAg. Drug resistance mutations were detected in 33 individuals, which amounted to 6.88%. The following mutations were found: S78T (27.27%), L80I (24.24%), S202I (15.15%), M204I/V (42.42%). The presence of polymorphic variants not described as drug resistant has also been shown in positions associated with the development of drug resistance to tenofovir, lamivudine, telbivudine and entecavir (L80F, S202I, M204R). When analyzing the MHR and the region of a determinant, mutations were detected in 318 (66.25%) of pregnant women. In 172 of them, which amounted to 54.09%, multiple mutations were found. The amino acid substitutions in 13 positions associated with HBsAg-negative hepatitis B and/or potentially affecting HBsAg antigenicity were identified. Conclusion. The high prevalence of immune escape and drug resistance mutations potentially associated with false-negative result of HBsAg screening, prophylaxis failure, and virological failure of therapy that has been identified among treatment naive pregnant women imposes a serious problem.

BackgroundWhen employing the transcription-mediated amplification method for screening blood donors, there are some non-discriminatory reactive results which are screening assay reactive but HBV-DNA discriminatory assay negative. This raises concerns regarding the possibility of false positives among donors, which may lead to permanent deferral of blood donors and affect blood supply. This study aimed to elucidate the infection status of these non-discriminatory reactive blood donors and develop and validate a model to predict individualized hepatitis B status to establish an optimal screening strategy.MethodsSupplementary tests were conducted on initial non-discriminating reactive donations to determine their HBV infection status, including repeat testing, viral load, serological marker detection, and follow-up. Primary clinical variables of the donors were recorded. Based on the Akaike information criterion, a stepwise forward algorithm was used to identify the predictive factors for information and construct a predictive model. The optimal screening strategy was determined through cost-effectiveness analysis.ResultsAt the Blood Center of Zhejiang Province, 435 cases of initial non-discriminatory reactive donations were collected over two successive periods and sub-categorized through repeated testing into the following three groups: non-repeated positive group, non-discriminated positive group, and non-repeated HBV-DNA positive group. The HBV discriminatory rate increased after repeated testing (110/435, 25.29%). According to supplementary tests, the HBV-DNA positivity rate was 65.52% (285/435), and occult HBV infection was a significantly different among groups (χ2 = 93.22, p

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). Dual HDV/HBV infection is associated with down-regulated HBV replication and fast progression to severe liver disease. Although HDV is transmissible through exposure to infected blood, data about HDV infection in blood donors remain scarce. Between 2011 and 2021, 869,633 donations were collected from prequalified donors in Dalian, China. In total, 1060 (0.12%) were confirmed HBsAg and/or HBV DNA-reactive. Subsequently, anti-HDV IgG was tested in 2175 donations, including 65 that tested HBsAg+ pre donation, 1017 confirmed HBV-positive (507 HBsAg+/HBV DNA+, 33 HBsAg+/DNA−, 477 HBsAg-/DNA+ (451 occult (OBI) and 26 acute infections)), 327 viral DNA non-repeated-reactive, 397 anti-HBc-only, and 369 anti-HBs-only. Two (0.09%) samples tested anti-HDV IgG weakly reactive but were unconfirmed by IgM and IgG repeat testing with alternative assays, suggesting an initial false reactivity. In addition, HDV testing in a subgroup of confirmed OBI donors, comprising 451 donors from Dalian and 126 archived samples of OBI donors from around the world, showed only one non-Chinese donor to be repeatedly anti-HDV-reactive, suggesting that HDV/HBV coinfection does not play a significant role in the genesis of OBI. The overall data suggested an extremely low prevalence of HDV infection among blood donors in Liaoning province, Northeast China. [ABSTRACT FROM AUTHOR]

Occult hepatitis B infection (OBI) is still a topic of debate worldwide. It is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. OBI may lead to the development of cirrhosis and hepatocellular carcinoma. It continues to present several unique challenges in organ transplantation despite the availability of an effective vaccine to prevent HBV infection and the introduction of oral therapy to treat HBV infection. HBV reactivation following organ transplantation can occur even in recipients with absent hepatitis B surface antigen and remains an important cause of morbidity and mortality. Concerning OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for both recipients of organ transplant and organ transplant donors especially in highly endemic areas of HBV. In the era of potent antivirals and with evolving knowledge, HBsAg (+) renal transplant candidates and recipients can be monitored and successfully treated. Kidney organs from HBsAg-negative and anti-HBc–positive donors should be considered for transplant candidates after weighing the risk-benefit ratio. All transplant candidates should receive HBV vaccination if they are not immune to facilitate receipt of an organ from a donor with anti-HBc seropositivity.

OBJECTIVES The objective of this study was to find the frequency of occult hepatitis B in patients presenting with Decompensated chronic liver disease. METHODOLOGY This descriptive, cross-sectional study was conducted at a tertiary care hospital at Peshawar-KP from 31st December 2021 to 31st May 2022.143 patients were enrolled. Informed consent was taken from all patients who were enrolled in this study. We included patients aged 18-60 years of either gender. All patients admitted to medical units or visiting Medical OPDs having decompensated Chronic liver disease were enrolled. A consecutive sampling technique was used to enroll patients for our study. Baseline characteristics, demographics and laboratory data were collected on predesigned proforma. All patients were screened for Hepatitis B infection by performing HBsAg with ELISA, and patients with negative surface antigens were eligible for the study. RESULTS Our study population age range was from 18 to 60 years, with a mean age of 43.30±8.00 years. There were 100 male (69.9%) patients and 43 female (30.1%) patients. Occult Hepatitis B was observed in 40(28%) patients with decompensated chronic liver disease. Among these patients, 26 were male, and 14 were female. Stratification for Occult Hepatitis B was done concerning age & gender to see any significant difference in distribution. There was no significant difference in the distribution of Occult Hepatitis B among different age groups and gender. CONCLUSION This study has shown that a significant proportion of decompensated chronic liver disease patients had evidence of occult hepatitis B infection. Methodology: This was a descriptive, cross sectional study that was conducted at a tertiary care hospital at Peshawar-KP from 31st December 2021 till 31st May 2022.. 143 patients were enrolled in this study. An informed consent was taken from all patients who were enrolled in this study. We included patients having age 18-60 years of either gender. All patients admitted in medical units or visiting Medical OPDs having decompensated Chronic liver disease were enrolled. Consecutive sampling technique was used to enroll patients for our study. Baseline characteristics, demographics and laboratory data was collected on predesigned proforma. All patients were screened for Hepatitis B infection by performing HBsAg with ELISA and patients with negative surface antigen were eligible for the study. Results: Our study population age range was from 18 to 60 years with mean age of 43.30±8.00 years There were 100 male (69.9%) patients and 43 female (30.1%) patients. Occult Hepatitis B was observed in 40(28%) of patients with decompensated chronic liver disease. Among these patients, 26 were male and 14 were female. Stratification for Occult Hepatitis B was done with respect to age & gender to see any significant difference in distribution. There was no significant difference in distribution of Occult Hepatitis B among different age groups and gender. Conclusion: This study has shown that significant proportion of decompensated chronic liver disease patients had evidence of occult hepatitis B infection.

Objective To investigate the HBV infection of TMA initially reactive but discriminatory test non-reactive samples(NDR) after the individual donation nucleic acid detection(ID-NAT)of TMA, and analyze its serological and molecular biological characteristics, so as to improve the safety of blood transfusion. Methods 121 970 samples of blood donors in the center from January 1, 2021 to December 31, 2021 were routinely tested by serology and nucleic acid of ID NAT, and 21 HBsAg(-)/ NDR samples were random collected. After the plasma samples were concentrated by ultra-high speed centrifugation, the gene sequences of BCP/PC, pre-S/S and S region were amplified by Nested PCR. The S region sequence was also sequenced to analyze the viral genotype and amino acid variation. At the same time, the original TMA retest discriminatory test was adopted, and Roche MPX 2.0 was used for ID-NAT, and the samples was not virus-concentrated.NDR samples were supplemented with electrochemiluminescence for anti-HBc and anti-HBs quantitative detection. Results Of the 121 970 samples screened, 117(0.096%) were found to be HBsAg(-)/NDR samples, of which 21 samples underwent a confirmation test. Sixteen(76.2%) cases were positive for HBV DNA by TMA retest, 7(33.3%) positive for HBV DNA by Roche MPX 2.0 ID-NAT, 9(42.9%) confirmed by Nested PCR, and 8(38.1%) positive by any two methods. Test results of serological markers were as follows: 17(80.9%) positive anti-HBc and 8(38.1%) positive anti-HBs. Eight infected cases were confirmed to have occult hepatitis B infection(OBI). The gene sequence of S region was successfully amplified and sequenced in 3 cases, all of which belonged to C type. Two mutations occurred in specimen S-2, all of which were outside MHR. There were 13 mutations in sample S-6, 6 mutations outside MHR and 7 mutations inside MHR. Conclusion Nearly 40% of NDR samples can still be detected as HBV DNA positive after virus concentration. Anti-HBc has a high detection rate, and there may be a potential risk of HBV transmission. The current NAT detection sensitivity should be improved. The amino acid mutation of S gene sequence may be related to OBI formation.

Abstract Aim To investigate the association of human leukocyte antigen (HLA)-DRB1 alleles and the variations of polymorphic amino acid changes in DRβ1 chain in Shaanxi Han population with Occult hepatitis B infection (OBI). Methods High-resolution HLA-DRB1 genotyping was performed in 107 OBI carriers and 280 normal controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Three-dimensional modeling was performed to explore the effect of the key residues on the HLA-DRB1 molecule. Results Strong susceptible association for allele DRB1*07:01 was observed in OBI carriers. The amino acid variation at HLA-DRβ1 molecule revealed susceptible associations for residues Gln4β, Val57β(P9), Ser60β(P9) and Val78β(P4), the amino acids Arg4β, Asp57β(P9), Tyr60β(P9) and Tyr78β(P4) showed protective associations. Conclusion Alleles DRB1*07:01 showed strong susceptible associations in OBI carriers. The amino acid variations in DRβ molecules revealed significant molecular markers for susceptibility and protection from OBI in Shaanxi Han population.

The aim of this study was to characterize mutations in the hepatitis B virus (HBV) genome associated with HBsAg-negative form of the disease in patients receiving hemodialysis replacement therapy. Materials and methods. We used blood plasma samples obtained from hemodialysis centers in St. Petersburg, Russia – 173 patients and 108 patients from Belgrade, Republic of Serbia. The samples were examined for the presence of serological (HBsAg, antibodies anti-HBs IgG, anti-HBcore IgG) and molecular-genetic (HBV DNA) markers of HBV followed by whole-genome sequencing and determination of clinically significant virus mutations. Results and discussion. Antibodies to hepatitis B were detected in 7.5 % and 11.1 % of patients from St. Petersburg and Belgrade, respectively. HBsAg was identified only in 1.1 % of cases in the group from Russia and in 0.9 % of cases in the group from Serbia. HBV DNA was determined in 2.8 % of the studied samples from both, patients from Saint-Petersburg and Belgrade. Phylogenetic analysis of 9 viral isolates showed that genotype D virus (88.9 %) prevailed as compared to genotype A (11.1 %) in the examined group. Among the samples obtained from patients from St. Petersburg, four belonged to the D2 sub-genotype, one to the D3 genotype. Four samples obtained from Belgrade patients belonged to different sub-genotypes – D1, D2, D3, A2, respectively. When analyzing the nucleotide sequences of the HBV genomes, mutations in the MHR region were detected in all cases, but only in HBsAg-negative isolates, mutations were revealed in the region of 124–147 amino acids, including mutations P120T, R122K, A128V, Q129R, M133I, G145R affecting the recognition of HBsAg by anti-HBs antibodies and associated with the resistance of the virus to the vaccine. The results of this study indicate that transmission of blood-borne viral hepatitis agent in the hemodialysis departments of the Russian Federation and the Republic of Serbia still exists. The prevalence of the latent chronic hepatitis B, coupled with the presence of vaccine escape mutations in all identified cases, indicates the need to pay close attention to the occurrence of the virus mutant variants in hemodialysis centers.

Occult hepatitis B infection (OBI) is still a topic of debate worldwide. It is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. OBI may lead to the development of cirrhosis and hepatocellular carcinoma. It continues to present several unique challenges in organ transplantation despite the availability of an effective vaccine to prevent HBV infection and the introduction of oral therapy to treat HBV infection. HBV reactivation following organ transplantation can occur even in recipients with absent hepatitis B surface antigen and remains an important cause of morbidity and mortality. Concerning OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for both recipients of organ transplant and organ transplant donors especially in highly endemic areas of HBV. In the era of potent antivirals and with evolving knowledge, HBsAg (+) renal transplant candidates and recipients can be monitored and successfully treated. Kidney organs from HBsAg-negative and anti-HBc-positive donors should be considered for transplant candidates after weighing the risk-benefit ratio. All transplant candidates should receive HBV vaccination if they are not immune to facilitate receipt of an organ from a donor with anti-HBc seropositivity. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum (usually HBV DNA < 200 IU/mL) or the liver but negativity for hepatitis B surface antigen (HBsAg). The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg. HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection., Case Summary: We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level. The patient was initially diagnosed as having OBI. However, sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein, which affects the formation of a disulfide bond that is associated with the formation of a loop. It is well known that there is an overlap between the S protein and Pol protein. We found that this new insertion site occurred in polymerase/reverse transcriptase domain, indicating that this insertion might be involved in HBV pathogenicity. The patient was finally diagnosed with a false OBI., Conclusion: An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). Dual HDV/HBV infection is associated with down-regulated HBV replication and fast progression to severe liver disease. Although HDV is transmissible through exposure to infected blood, data about HDV infection in blood donors remain scarce. Between 2011 and 2021, 869,633 donations were collected from prequalified donors in Dalian, China. In total, 1060 (0.12%) were confirmed HBsAg and/or HBV DNA-reactive. Subsequently, anti-HDV IgG was tested in 2175 donations, including 65 that tested HBsAg+ pre donation, 1017 confirmed HBV-positive (507 HBsAg+/HBV DNA+, 33 HBsAg+/DNA−, 477 HBsAg-/DNA+ (451 occult (OBI) and 26 acute infections)), 327 viral DNA non-repeated-reactive, 397 anti-HBc-only, and 369 anti-HBs-only. Two (0.09%) samples tested anti-HDV IgG weakly reactive but were unconfirmed by IgM and IgG repeat testing with alternative assays, suggesting an initial false reactivity. In addition, HDV testing in a subgroup of confirmed OBI donors, comprising 451 donors from Dalian and 126 archived samples of OBI donors from around the world, showed only one non-Chinese donor to be repeatedly anti-HDV-reactive, suggesting that HDV/HBV coinfection does not play a significant role in the genesis of OBI. The overall data suggested an extremely low prevalence of HDV infection among blood donors in Liaoning province, Northeast China.

Occult hepatitis B infection (OBI) is defined by the persistence of the hepatitis B virus (HBV) genome in the liver of individuals testing negative for hepatitis B surface antigen (HBsAg). Hepatitis B core antibody (anti‐HBc) is the serological marker that indicates HBV exposure. The impact of anti‐HBc and OBI on patients with chronic hepatitis C remains unclear. The aim of the present study was to determine the prevalence of anti‐HBc and OBI and to evaluate their impact on the clinical and pathological outcomes of patients with chronic hepatitis C. The study included 59 HBsAg‐negative chronic hepatitis C patients who underwent a liver parenchymal biopsy. The presence of HBV DNA was investigated using an in‐house nested PCR method. OBI was detected in 16 (27.1%) of the 59 cases and also in 10 (62.5%) of 22 (37.3%) anti‐HBc‐positive patients. None of the patients had positive serum HBV DNA. OBI was associated with the presence of anti‐HBV antibodies (P < 0.05). There was also an association between anti‐HBc positivity and the activity grades and fibrosis stages of the liver and also a prevalence of liver steatosis (P < 0.05). Positive anti‐HBc results may predict OBI and may also be associated with the progression of liver injury in HBsAg‐negative patients with chronic hepatitis C. Therefore, it is suggested that patients with chronic hepatitis C should be screened for anti‐HBc positivity, and anti‐HBc‐positive patients should be carefully evaluated for disease progression. [ABSTRACT FROM AUTHOR]

Nucleic acid Amplification testing (NAT) has helped improve blood safety and detect window period and Occult Hepatitis B infections (OBI) This study was aimed at determining the following in blood donors: 1. seroprevalence of HIV, HBV & HCV, malarial parasite and Syphlis 2. NAT and seroyield for HIV, HBV and HCV 3. viral load in NAT yield donations 4. Pattern of HBV serological markers in HBV NAT yield donations 80,809 blood donations were screened over an 8 year period (2012–2019) for antiHIV I and II, HBsAg, antiHCV antibodies, malarial parasite and VDRL. Seronegative samples were tested by NAT using a multiplex PCR in a pool of six. NAT yield samples were tested for viral load and HBV serological markers. Seropositive samples were tested for NAT and checked for seroyield. SPSS windows version 24.0 was used for statistical analysis. 1.07% of blood donors were found to be seropositive with 0.08%, 0.86%, 0.09%, 0.03% and 0 for anti HIV I and II, HBsAg, antiHCV, VDRL and Malarial parasite respectively. Out of 79,938 seronegative samples, 20 samples (0.025%) were NAT positive for Hepatitis B with a NAT yield OF 1:3997. Out of the 20 NAT positive samples, 17 were OBI and three were window period infections. 14 NAT yield samples subjected to a HBV viral load assay showed a range of < 6–146 IU/ml. Minipool NAT in pools of six is able to indentify both OBI and window period infections. NAT could significantly improve the blood safety in a resource limited setting like India. [ABSTRACT FROM AUTHOR]

Abstract Background & aim: Occult hepatitis B virus infection in blood donors threats the safety of the blood supply. It is characterized by detection of low viral DNA in the serum subjects who have negative test for Hepatitis B surface antigen (HBsAg). The aim of this study was to assess the prevalence of occult hepatitis B virus infection among HBsAg negative and HBcAb positive in blood donors of Bushehr blood transfusion organization Methods: The present cross-sectional study was conducted on 1000 blood donors referring to Bushehr blood transfusion organization between November 2017 and January 2019. All subjects were negative for HBsAg and were tested for HBcAb by use of ELISA technique. The samples that were positive for HBcAb marker also analyzed for the presence of viral DNA by Real time PCR. The data were analyzed using SPSS Ver. 22.0 and chi-square tests Results: 30 (3%) out of 1000 samples were HBcAb positive. Of these 30 samples, 29 (97%) were male and 1 (3%) was female. A significant association was found between level of education and HBcAb positive (p=0.028). Also, there was a significant association between marital status and HBcAb positive (p=0.001). HBV-DNA was not detected in any of the cases with isolated HBcAb. The results showed no significant relationship between HBcAb positive and occult hepatitis B virus infection (p> 0.05) Conclusion: Although the viral genome was not present in any of the HBcAb positive and HBsAg negative blood donors in Bushehr Blood Transfusion Organization, but to improve the health of donated blood, it is recommended that HBcAb testing and PCR method be used to determine the prevalence of occult hepatitis B infection in HBsAg-negative blood donors in a wider range of blood donors. Therefore, serological HBsAg testing alone cannot detect occult hepatitis B infection in blood donors

ABSTRACT BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.

Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co‐exist. Furthermore, much evidence suggests a role of OBI in the hepato‐carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non‐HCV‐related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV‐DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69–0.96) in the general population, 16.26% (95% CI:10.97–22.34) in HIV patients, 13.99% (95% CI:8.33–20.79) in patients with other liver diseases, 4.25% (95% CI:1.64–7.87) in haemodialysis patients and 5.14% (95% CI:2.26–9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high‐risk populations to design preventive and management strategies. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of human leukocyte antigen (HLA)-DRB1 alleles and the variations of polymorphic amino acid changes in DRβ1 chain in Shaanxi Han population with Occult hepatitis B infection (OBI). Methods: High-resolution HLA-DRB1 genotyping was performed in 107 OBI carriers and 280 normal controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Three-dimensional modeling was performed to explore the effect of the key residues on the HLA-DRB1 molecule. Results: Strong susceptible association for allele DRB1*07:01 was observed in OBI carriers. The amino acid variation at HLA-DRβ1 molecule revealed susceptible associations for residues Gln4β, Val57β(P9), Ser60β(P9) and Val78β(P4), the amino acids Arg4β, Asp57β(P9), Tyr60β(P9) and Tyr78β(P4) showed protective associations. Conclusion: Alleles DRB1*07:01 showed strong susceptible associations in OBI carriers. The amino acid variations in DRβ molecules revealed significant molecular markers for susceptibility and protection from OBI in Shaanxi Han population. [ABSTRACT FROM AUTHOR]

Abstract Background The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. Methods 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. Results Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. Conclusion These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.

Aim: Occult hepatitis B infection (OBI) is life threatening and has a high mortality rate despite applying antiviral treatments in cancer patients. This study aimed to investigate the prevalence of OBI in patients undergoing chemotherapy in Iran. Materials & methods: A total of 342 patients undergoing chemotherapy were enrolled. OBI detection in anti-HBc positive individuals was conducted using nested PCR. Results: Among 342 subjects, 103 (30.1%) were positive for anti-HBc. Fifteen (14.6%) cases of 103 anti-HBc positive samples were also positive for HBsAg. Overall, HBV DNA was positive in three (3.4%) of 88 anti-HBc subjects. Conclusion: Our results indicated that OBI might occur in almost one in 25 anti-HBc-positive patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p < 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p < 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p < 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7–338.3% vs. extracellular) and its fluorescence intensity (1.5–2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p < 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs. [ABSTRACT FROM AUTHOR]

The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p < 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p < 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p < 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7–338.3% vs. extracellular) and its fluorescence intensity (1.5–2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p < 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs.

BackgroundMost Chinese Blood Centers adopted mini pool (MP) nucleic acid testing (NAT) for HBV screening due to high cost of Individual donation (ID) NAT, and different proportions of MP-reactive but ID-non-reactive donations (MP+/ID−, defined as non-resolved donations) have been observed during daily donor screening process. Some of these non-resolved donations are occult HBV infections (OBIs), which pose potential risk of HBV transmission if they are not deferred. This study is aimed to further analyze these non-resolved donations.MethodsThe non-resolved plasma samples were further analyzed by serological tests and various HBV DNA amplification assays including quantitative PCR (qPCR) and nested PCR amplifying the basic core and pre-core promoter regions (BCP/PC; 295 base pairs) and HBsAg (S) region (496 base pairs). Molecular characterizations of HBV DNA+ non-resolved samples were determined by sequencing analysis.ResultsOf 17,226 MPs from 103,356 seronegative blood donations, 98 MPs were detected reactive for HBV. Fifty-six out of these 98 (57.1%) reactive MPs were resolved as HBV DNA+, but the remaining 42 pools (42.9%, 252 donations) were left non-resolved with a high rate (53.2%) of anti-HBc+. Surprisingly, among 42 non-resolved MPs, 17 contained one donation identified as OBIs by alternative NAT assays. Sequence analysis on HBV DNAs extracted from these OBI donations showed some key mutations in the S region that may lead to failure in HBsAg detection and vaccine escape.ConclusionA total of 53.2% of the non-resolved donations were anti-HBc+, and OBIs were identified in 40.5% of these non-resolved pools. Therefore, non-resolved donations with anti-HBc+ might pose potential risk for HBV transmission. Our present analysis indicates that anti-HBc testing in non-resolved donations should be used to identify OBIs in order to further increase blood safety in China.

Objective: Occult hepatitis B infection (OHBI) appears to have a higher prevalence in populations at high risk for hepatitis B virus (HBV) infection with concomitant liver disease. The aim was to assess the prevalence of OHBI in a sample of human immunodeficiency virus -1 positive and HBV surface antigen-negative (HIV-1+/HBsAg-) Turkish patients.Methods: Ten centres in Turkey were included in the study. Patients were selected on the basis of a power calculation with a known population size of HIV-positive patients and a reported prevalence of OHBI. Gender, age, occupation, place of residence, treatment and clinical status, and laboratory results, including immunodeficiency panel, antibody tests, hemogram, biochemistry, and coagulation studies were evaluated retrospectively.Results: The number of HIV-infected patients followed in these centres was 3172 and the sample population numbered 278. All 278 were HBsAg negative. The mean age of the sample was 37.2 ± 13.1 years and 235 (84.5%) were male. All but one patient (99.6%) had been treated with antiretroviral therapy. Of the 278 patients, 169 (60.6%) were positive for Anti-HBs and 125 (44.8%) were positive for Anti-HBc IgG. HIV RNA was detected in 203/278 (73%) of the patients. Four HBV DNA (1.4%) were diagnosed with OHBI. There was no significant difference in hemogram, hemoglobin or bilirubin concentrations in those with OHBI compared with the other patients.Conclusion: In a representative sample of HIV+ patients from 10 Turkish centres, the prevalence of OHBI was found to be 1.4%. In HIV positive patients, it is important to identify those with OHBI for optimal clinical management and prognosis. [ABSTRACT FROM AUTHOR]

Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotype distribution, HBV mutations and coinfections, which may have important clinical implications in public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations. [ABSTRACT FROM AUTHOR]

Background: Most Chinese Blood Centers adopted mini pool (MP) nucleic acid testing (NAT) for HBV screening due to high cost of Individual donation (ID) NAT, and different proportions of MP-reactive but ID-non-reactive donations (MP+/ID−, defined as non-resolved donations) have been observed during daily donor screening process. Some of these non-resolved donations are occult HBV infections (OBIs), which pose potential risk of HBV transmission if they are not deferred. This study is aimed to further analyze these non-resolved donations. Methods: The non-resolved plasma samples were further analyzed by serological tests and various HBV DNA amplification assays including quantitative PCR (qPCR) and nested PCR amplifying the basic core and pre-core promoter regions (BCP/PC; 295 base pairs) and HBsAg (S) region (496 base pairs). Molecular characterizations of HBV DNA+ non-resolved samples were determined by sequencing analysis. Results: Of 17,226 MPs from 103,356 seronegative blood donations, 98 MPs were detected reactive for HBV. Fifty-six out of these 98 (57.1%) reactive MPs were resolved as HBV DNA+, but the remaining 42 pools (42.9%, 252 donations) were left non-resolved with a high rate (53.2%) of anti-HBc+. Surprisingly, among 42 non-resolved MPs, 17 contained one donation identified as OBIs by alternative NAT assays. Sequence analysis on HBV DNAs extracted from these OBI donations showed some key mutations in the S region that may lead to failure in HBsAg detection and vaccine escape. Conclusion: A total of 53.2% of the non-resolved donations were anti-HBc+, and OBIs were identified in 40.5% of these non-resolved pools. Therefore, non-resolved donations with anti-HBc+ might pose potential risk for HBV transmission. Our present analysis indicates that anti-HBc testing in non-resolved donations should be used to identify OBIs in order to further increase blood safety in China. [ABSTRACT FROM AUTHOR]

The occult HBV infection generally defined as presence of hepatitis B viral DNA on the blood and/or liver associated with detectable or undetectable levels of anti-HBV antibodies at individuals whom gave negative result for HBsAg. Sample collection through taking 3-5 milliliter of blood that aseptically drawn from 1473 individuals from different Iraqi provinces; 1412 of them explained negative result with HBsAb test were examined for OBI through use RT-PCR, in addition to ELISA assay searching anti-HBc and anti-HBs antibodies. The infection rate with OBI was 3.75%, percentages of infection in general population, Thalassemic patients, Hemodialysis patients, Diabetic patients and HIV infected patients were 2.32%, 8.82%, 6.83%, 5.51% and 6.97%, respectively. The infection at non-immunized patients, 62.2% was significantly higher than that at immunized patients, 37.7%. The age group >60 recorded highest percentage,5.94%, in the general population. In conclusion, rhis study has demonstrated the prevalence of OBI in different Iraqi regions, according to our knowledge; this is the first that recorded OBI in the country, besides to offering valuable information concerning the viral spreading and the epidemiological picture of this infection. [ABSTRACT FROM AUTHOR]

Background: The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. Methods: 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. Results: Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients. Conclusion: These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases. [ABSTRACT FROM AUTHOR]

Background: Behcet's disease (BD) is a chronic multisystem vasculitis with an unknown etiology. During the past years, several reports are published on the occult hepatitis B infection (OBI), the presence of hepatitis B virus (HBV) DNA in the absence of HBsAg, in rheumatic diseases. Objectives: The current study aimed to, firstly, investigate the prevalence of OBI in patients with BD, and, secondly, its potential association with the clinical and therapeutic status of BD. Methods: HBV serological markers and HBV DNA were evaluated in 220 consecutive BD patients to detect OBI. Demographic and clinical data of OBI positive and negative groups were compared. Results: The mean age of patients was 39.24 (±10.57), and 134 (62.9%) were male. The mean disease duration was 14.13 (±8.63) years. No HBsAg positive case was found, but HBV DNA was found in 19 (8.6%) patients. The median viral load value was 475.84 copy/mL. We compared clinical data of 10 OBI positive and 156 OBI negative BD patients with complete and accessible data. There was no difference between the two groups concerning demographic characteristics (age, sex, and disease duration), different clinical manifestations, or types of medications (immunomodulatory, cytotoxic, and corticosteroids). Conclusions: This is the first study showing a rather high prevalence of OBI among BD patients. We did not find any correlation between OBI positivity and different clinical manifestations, medications, or HLA-B51. Further studies are needed on a larger group of patients and by molecular HBV evaluation (as well as serologic) regarding this possible association. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) is a globally prevalent infection, with its frequency being influenced by the prevalence of hepatitis B virus (HBV) infection in a particular geographic region, including Africa. OBI can be transmitted through blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma (HCC). The associated HBV genotype influences the infection., Aim: To highlight the genetic diversity and prevalence of OBI in Africa., Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed, Google Scholar, Science Direct, and African Journals Online for published studies on the prevalence and genetic diversity of OBI in Africa., Results: The synthesis included 83 articles, revealing that the prevalence of OBI varied between countries and population groups, with the highest prevalence being 90.9% in patients with hepatitis C virus infection and 38% in blood donors, indicating an increased risk of HBV transmission through blood transfusions. Cases of OBI reactivation have been reported following chemotherapy. Genotype D is the predominant, followed by genotypes A and E., Conclusion: This review highlights the prevalence of OBI in Africa, which varies across countries and population groups. The study also demonstrates that genotype D is the most prevalent., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Abstract INTRODUCTION: HBV and HIV have identical transmission routes. The aim of this study was to determine the prevalence of HBV in HIV patients and to detect the presence of occult HBV infection. METHODS: All samples were tested for serology markers and using qPCR. RESULTS: This study included 232 individuals, out of which 36.6% presented with HBV markers and 11.8% presented with HBsAg or HBV-DNA, including 3 patients that showed OBI. CONCLUSIONS: We observed a high prevalence of HBV among HIV patients. In addition, the results suggest that OBI can occur in patients with serological profiles that are indicative of past infection. Therefore, the application of molecular tests may enable the identification of infections that are not evident solely based on serology.

INTRODUCTION: Occult hepatitis B infection (OBI) may contribute to liver damage and variable therapeutic response in patients with chronic hepatitis C (CHC) infection. AIMS: To study the prevalence of OBI and to evaluate its impact and/or that of anti-HBc total seropositivity on clinical outcomes and response to directly acting antiviral (DAA) therapy in CHC-infected patients. SETTINGS AND DESIGN: A retrospective cohort study was conducted in a tertiary care liver hospital from January to May 2017. SUBJECTS AND METHODS: Eighty HBsAg-negative CHC patients who were initiated on DAA therapy were retrospectively included. Archived pretreatment baseline plasma samples were retrieved and tested for quantitative HBV DNA, anti-HBs, and anti-HBc total antibodies. HCV RNA, genotype, clinical, biochemical and histopathological parameters & treatment response data were obtained from the hospital information system. STATISTICAL ANALYSIS USED: Comparison of continuous variables was done by Mann–Whitney and Kruskal–Wallis tests and categorical variables by Fisher’s exact test or Pearson’s Chi-square test. RESULTS: Prevalence of OBI was 1.25%. Anti-HBc total positivity was seen in 25% patients. Based on anti-HBc total status, patients were categorized into two groups namely Group 1 (anti-HBc positive) and Group 2 (anti-HBc negative). Group 1 patients were further categorized into three subgroups based on signal/cutoff (S/Co) of HBc total antibody semi-quantitative values. HBc total antibody levels did not influence the severity of CHC disease. Comparative evaluation of parameters such as median log10 baseline RNA (P = 0.929 and 0.464), median alanine aminotransferase (ALT 0) (P = 0.519 and 0.449), ALT at 12 weeks (P = 0.875 and 0.594), sustained virological response (SVR) at 12 weeks (P = 0.405 and 0.263) and SVR at 24 weeks (P = 0.265 and 0.625) between Groups 1 and 2 and among three categories within Group 1, respectively, were not found to be statistically significant. Conclusions: Very low prevalence of OBI was seen in CHC patients. HBc total antibody levels did not influence clinical outcome and response to DAA therapy in this cohort.

Objectives: To identify blood donors with occult hepatitis B infections (OBIs), determine the prevalence of antibody to hepatitis B core antigen (anti-HBc) positivity and estimate the impact of anti-HBc screening on donor deferral at CETS-Veracruz (Mexico). Background: Hepatitis B virus infection is a major concern in transfusion medicine. Mexican regulations only mandate screening for hepatitis B surface antigen (HBsAg), and there are no requirements regarding testing for anti-HBc or use of a nucleic acid test (NAT). There is, therefore, limited information about the prevalence of anti-HBc positivity and occult hepatitis B among blood donors in Mexico. Methods: This retrospective study examined individuals who donated blood to CETS-Veracruz from June 2014 to June 2017. All donors were serologically examined according to Mexican health regulations, and the prevalence of anti-HBc positivity was determined. A NAT was used to identify individuals with OBIs. Results: We analysed the data of 28 016 blood donors. Over 4 years, the average prevalence of anti-HBc positivity was 1.05%. The risk factors for anti-HBc positivity were low education and age over 50 years. There were nine donors with OBIs. Conclusion: The presence of donors with OBIs in CETS-Veracruz and other Mexican blood banks highlights the need to mandate the implementation of anti-HBc screening in Mexico. [ABSTRACT FROM AUTHOR]

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty‐seven hepatitis B surface antigen (HBsAg)‐positive/HBV DNA‐positive blood donors served as control group for comparison. Occult HBV‐related mutations with a high incidence (P <.05) in the S gene were identified. To further verify these occult infection‐related mutations, a conservative full‐gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection‐related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P <.05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P <.05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P <.05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P <.0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) is defined as the lack of detectable HBsAg in serum, despite the presence of intrahepatic viral DNA, and low levels of covalently closed circular DNA (cccDNA). Since the hemodialysis patients are at a greater disadvantage if they are a carrier of Hep B, as it can lead to OBI this study was designed to determine the prevalence of OBI in hemodialysis patients residing in Zanjan, Iran. Methods: We conducted an anti-HBc test (ELISA) on 166 HBsAg negative hemodialysis patient samples. OBI was evaluated using seropositive (anti-HBc and/or anti-HBs) and seronegative (anti-HBc and anti-HBs) using nested PCR. Results: Out of the total hemodialysis patients sampled, the study consisted of 58.4% male and 41.6% female participants. The age of the study group ranged from 58.89±15.49, and had received approximately 28.27±27.43 years of dialysis. Additionally, 5.4% of patients had a history of blood transfusions, while 58.4% were vaccinated against the hepatitis B virus (HBV). Moreover, 23.5% patients were anti-HBc positive, while 76.5% patients tested negative. Lastly, 66.3% of the patients were positive for anti-HBs, whereas 33.7% were negative for anti- HBs. Overall, the study revealed that the prevalence of OBI was 6%, and HBV DNA was detected in 2.1% of individuals who were vaccinated against hepatitis B (p < 0.01). Conclusions: Though no significant difference between the prevalence of OBI to the patients' age, sex, duration of dialysis, or history of blood transfusion was identified, however, a strong correlation between the prevalence of OBI to HBV vaccination was found. [ABSTRACT FROM AUTHOR]

• Hemodialysis procedures pose the risk of transmitting viral hepatitis infections. • A high prevalence of occult hepatitis B virus exists in chronic hepatitis C virus-infected hemodialysis patients. • No evident clinical impact accompanies either SEN virus or torque teno virus viremia. Egypt ranks first regarding the prevalence of hepatitis C virus (HCV) infection. Many patients have concomitant diseases like kidney disorders requiring hemodialysis, a procedure carrying the hazard of transmitting other hepatitis viruses. The purpose of this study was to investigate for occult hepatitis B virus (HBV), SEN virus (SENV), and torque teno virus (TTV) among chronic HCV patients on maintenance hemodialysis to identify their impacts. A total of 325 hemodialysis patients were enrolled and divided into two groups based on HCV RNA testing results. Blood samples were collected before hemodialysis. Sera were tested for hepatitis B core antibodies (anti-HBc) and hepatitis B surface antibodies (anti-HBs) using ELISA. HBV, SENV, and TTV DNA were detected by PCR. The serum alanine aminotransferase (ALT) level was measured. Anti-HBc and HBV DNA were detected in 73.1% and 50.8% of group 1 versus 36.4% and 22.6% of group 2. The serum ALT level was higher in group 1 than group 2. SENV was detected in 11.5% of group 1 versus 8.2% of group 2. TTV was detected in 29% of group 1 versus 27% of group 2. There is an increased prevalence of occult HBV in our locality among chronic HCV patients undergoing hemodialysis. The existence of SENV and TTV viremia has no clinical impact. [ABSTRACT FROM AUTHOR]

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• HBV-DNA was undetectable in recipients and donors before kidney transplant. • At three-months follow-up, 2.7% of recipients were positive for HBV. • Similar studies should be performed in Mexican patients with solid organ transplant. • Clinical assessment in OBI patients must be routinely performed. Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. Our aim was to determine OBI frequency in serum and genomic DNA in patients undergoing renal transplant and their cognate donors in a selected population from Western Mexico. Blood samples were obtained from 94 donors and their cognate recipients (188 participants) before kidney transplantation. Identification of HBV DNA was carried-out by nested (S-region) and semi-nested (Pol-region) PCR in both genomic and serum DNA samples from 188 participants at pre-surgical stage and from a subset of 73 recipients at three-month follow-up. HBV-DNA was not detected in either genomic or serum DNA samples from recipients or donors prior to transplantation. After three-months of follow-up, 2 out of 73 (2.7%, 95% CI: 0.9–11.9%) recipients were positive to HBV-DNA (Pol-region) in genomic DNA samples using a high sensitivity Taq DNA polymerase. OBI incidence in recipients of kidney transplant may be higher than previously recognized. Detection of HBV-DNA was higher in genomic DNA than in serum samples using a high sensitivity Taq DNA polymerase. To the best of our knowledge, this is the first report regarding this specific topic in Mexicans. [ABSTRACT FROM AUTHOR]

Objective To investigate the KIR gene polymorphisms and their features in unpaid blood donors with occult hepatitis B infection(OBI). Methods A total of 105 unpaid blood donors with OBI were screened out from the unpaid blood donors in Chongqing Blood Center from 2016 to 2019. Peripheral blood samples were collected for DNA extraction and KIR genotyping. KIR genotype ID and haplotype were determined based on a comparative analysis of the KIR genotype database published on the international allele website. Genotype frequency was calculated according to the equation of genotype frequency( F) =, in which f represented the proportion of a phenotype of KIR gene. The chi-square test was used for comparison of categorical data between groups. Results All 105 OBI blood donors had the KIR genes 2 DL4, 3 DL2, 3 DL3, and pseudogene 3 DP1. The KIR genes 2 DL1, 2 DL3, 3 DL1, 2 DS4, and pseudogene 2 DP1 had an F value of > 70%, among which the KIR gene 2 DS4 with exon 5 deletion had an F value of 26. 32%. The KIR genes with low frequency(< 30%)were 2 DL2, 2 DL5, 2 DS1, 2 DS2, 2 DS3, 2 DS5, and 3 DS1. Compared with the Han population in Chongqing, Hebei, and Jiangsu and the Tibetan population in Lasa, the OBI blood donors had a significantly lower frequency of the KIR 2 DL3 gene(χ2= 9. 598, 12. 236, 13. 719, and 10. 974, all P < 0. 05). There were significant differences in the frequencies of 2 DL2, 2 DL5, 2 DS2, and 2 DS3 between the OBI blood donors and the Uyghur population in Urumqi(χ2= 16. 215, 6. 981, 19. 498, and 11. 819, all P < 0. 05). There were significant differences in the frequencies of 2 DL2, 2 DS1, 2 DS2, 2 DS3, and 2 DS4 between the OBI blood donors and the Caucasians(χ2= 22. 477, 3. 877, 34. 937, 6. 909, and 4. 271, all P < 0. 05). Compared with the Han population in Chongqing, the OBI blood donors had a significant increase in the frequency of KIR 2 DS4* del(χ2= 12. 911, P < 0. 05). Compared with the population with chronic HBV infection, the OBIblood donors had significant reductions in the frequencies of 2 DS2 and 2 DS3(χ2= 13. 005 and 8. 289, P < 0. 05) and significant increases in the frequencies of 2 DS4 and 3 DL1(χ2= 10. 032 and 3. 865, P < 0. 05). Compared with the population with ankylosing spondylitis, the OBI blood donors had significant reductions in the frequencies of 2 DL3 and 2 DS3(χ2= 7. 851 and 16. 504, P < 0. 05). Compared with the gays with HIV-AIDS, the OBI blood donors had significant increases in the frequencies of 2 DS4 and 3 DL1(χ2= 15. 491 and 4. 475, P <0. 05). There were significant differences in the frequencies of 2 DL1, 2 DL2, 2 DL3, 2 DL4, 2 DL5, 2 DS4, 3 DL2, 3 DL3, and 2 DP1 between the OBI blood donors and the population with sporadic acute hepatitis E(χ2= 4. 448, 30. 934, 17. 942, 15. 638, 4. 227, 13. 802, 32. 667, 35. 653, and 36. 566, P < 0. 05). A total of 21 KIR genotypes were found, among which genotype AA1 had the highest frequency of 49. 52%, followed by genotype Bx2(18. 1%). Conclusion OBI blood donors have unique features of KIR gene polymorphisms. KIR2 DL3 is a potential protective gene for OBI, while KIR 2 DS4 * del is a potential susceptibility gene for OBI. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) has been described in various clinical settings including after hepatitis B virus (HBV) immunization. The purpose of study was to characterize the prevalence of OBI among immunized children from a subset of general population and the parents of OBI‐positive cases. Methods: Sera of 1200 children from general population who have been previously immunized by HBV vaccine were assayed for anti‐HBs. 660 were randomly selected for HBV DNA testing by different polymerase chain reaction (PCR) methods and were analysed by direct sequencing on surface genes. Results: None of participants were positive for HBsAg and anti‐HBc. 549 (45.7%) and 651 (54.3%) cases had anti‐HBs > 10 mIU/mL (responders) and < 10 mIU/mL (nonresponders) respectively. Of 660 selected specimens, 91 (16%) of children were positive for OBI. 23 (25.2%) and 68 (74.8%) of HBV DNA positive cases were belonged to responders and nonresponders, respectively, showing significant difference (P <.001). The mean levels of anti‐HBs in OBI‐positive and OBI‐negative groups, showed no considerable variations. The mean viral load for OBI‐positive cases showed substantial differences between responders and nonresponders (P =.007). Of 49 parents (98 individuals) of OBI‐positive children 11 (22%) and 18 (36%) were positive for anti‐HBc and anti‐HBs respectively. Molecular testing was positive in 32 subjects (16 couples, 32.6%). In total, 6 mothers and 11 fathers were positive for OBI. Conclusion: A proportion of OBI‐positive vaccinated children could be existed in different populations. This finding could be arisen from vertical HBV transmission or vertical OBI possibly from their parents. [ABSTRACT FROM AUTHOR]

Background: When employing the transcription-mediated amplification method for screening blood donors, there are some non-discriminatory reactive results which are screening assay reactive but HBV-DNA discriminatory assay negative. This raises concerns regarding the possibility of false positives among donors, which may lead to permanent deferral of blood donors and affect blood supply. This study aimed to elucidate the infection status of these non-discriminatory reactive blood donors and develop and validate a model to predict individualized hepatitis B status to establish an optimal screening strategy., Methods: Supplementary tests were conducted on initial non-discriminating reactive donations to determine their HBV infection status, including repeat testing, viral load, serological marker detection, and follow-up. Primary clinical variables of the donors were recorded. Based on the Akaike information criterion, a stepwise forward algorithm was used to identify the predictive factors for information and construct a predictive model. The optimal screening strategy was determined through cost-effectiveness analysis., Results: At the Blood Center of Zhejiang Province, 435 cases of initial non-discriminatory reactive donations were collected over two successive periods and sub-categorized through repeated testing into the following three groups: non-repeated positive group, non-discriminated positive group, and non-repeated HBV-DNA positive group. The HBV discriminatory rate increased after repeated testing (110/435, 25.29%). According to supplementary tests, the HBV-DNA positivity rate was 65.52% (285/435), and occult HBV infection was a significantly different among groups (χ 2  = 93.22, p  < 0.01). The HBV serological markers and viral load in the non-repeated positive group differed from those in the other two groups, with a lower viral load and a higher proportion of false positives. The predictive model constructed using a stepwise forward algorithm exhibited high discrimination, good fit, high calibration, and effectiveness. A cost-effectiveness analysis indicated that utilizing repeated discriminatory testing and the predictive model is an extremely beneficial screening approach for non-discriminatory reactive blood donors., Conclusion: Nearly two-third (65.52%) of the non-discriminatory reactive blood donors were HBV-DNA positive. Our innovative approach of constructing a predictive model as a supplementary screening strategy, combined with repeated discriminatory experiments, can effectively identify the infection status of non-discriminatory reactive blood donors, thereby increasing the safety of blood transfusions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Hu, Wang, Wu, Dong, Liu and Hu.)

Aim: We analyzed the role of mutations on the conformational structure of hepatitis B surface antigen (HBsAg) among HIV-1 positive patients who were infected with occult hepatitis B. Methods: The effects of the potential impact of amino-acid substitutions on the 3D structures of the HBsAg and molecular ducking were investigated using bioinformatics software. Results: Mutations classified in seven groups in accordance with their positions in occult hepatitis B virus infection patients. Some substitutions of residues could linearize the 'a' determinant loops. The affinity of binding in mutant HBsAg structures to MAb 12 was lower compared with the wild ones. T123I and P127L substitutions were undergone decrease in HBsAg antigenicity. Conclusion: These findings could be beneficial for a better understanding of hepatitis B virus antigen/antibody interactions. [ABSTRACT FROM AUTHOR]