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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., 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 Jiang, Tian, Song, Meng, Yang, Qiao and Zou.)

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.)

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., (© 2024 British HIV Association.)

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., (© 2024. The Author(s).)

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.)

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.)

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.

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.

Background: Intrahepatic cholangiocarcinoma (ICC) is a poorly understood and aggressive malignancy with increasing incidence and mortality. Hepatitis B virus (HBV) infection is recognized as one of the important risk factors of ICC. There are few reports focusing on whether isolated antibody to hepatitis B core antigen (isolated anti-HBc, IAHBc) have prognostic role in ICC, while positive hepatitis B surface antigen (HBsAg) has been reported to be associated with the prognosis of ICC. The aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection, in order to identify those who have the high risk of ICC recurrence in the early stage., Methods: We divided 209 ICC patients who underwent curative resection into 4 groups: group I (n = 40), HBsAg (-)/antibody to hepatitis B surface antigen (anti-HBs) (-)/anti-HBc (+); group II (n = 70), HBsAg (+)/anti-HBc (-); group III (n = 55), HBsAg (-)/anti-HBs (+)/anti-HBc (+); and group IV (n = 44), HBsAg (-)/anti-HBc (-). We compared the recurrence-free survival (RFS) and overall survival (OS) among these four groups., Results: The median follow-up time was 16.93 months (range 1-34.6 months). The 1- and 2-year RFS and OS rates were 60% and 42%, and 78% and 63% respectively in all patients. Compared to the whole non-IAHBc patients (group II + group III + group IV), IAHBc patients (group I) showed significantly lower RFS at 1 year (39.8% vs. 64.4%, P = 0.001) and 2 years (20.7% vs. 46.7%, P = 0.001). When compared to other three individual groups, IAHBc patients (group I) also had the lowest RFS. We did not find significant difference in OS among the four groups. Further multivariate analysis revealed that IAHBc was an independent risk factor of RFS., Conclusions: IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection., (Copyright © 2022. Published by Elsevier B.V.)

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., (© 2022 The Societies and John Wiley & Sons Australia, Ltd.)

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., Competing Interests: Conflict of interestThe authors have no disclosures of conflicts of interest., (© Indian Society of Hematology and Blood Transfusion 2021.)

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., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

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., (© 2022 John Wiley & Sons Ltd.)

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 Gln 4β , Val 57β (P9), Ser 60β (P9) and Val 78β (P4), the amino acids Arg 4β , Asp 57β (P9), Tyr 60β (P9) and Tyr 78β (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., (© 2022. The Author(s).)

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., 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 © 2021 Wang, Liao, Xie, Gao, Wang, Huang, Xu, Liao, Shan, Zheng, Rong, Li and Fu.)

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.

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., 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 © 2021 Ye, Zhao, Li, Li, Zheng, Xiong, Zeng, Xu and Chen.)

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.

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., (© 2020 British Blood Transfusion Society.)

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., (© 2020 John Wiley & Sons Ltd.)

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)., Conclusion: 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.

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: 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 log 10 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., Competing Interests: There are no conflicts of interest.

Occult hepatitis B infection (OBI) is a cause of concern while screening the blood donors to prevent transfusion-related transmission of infection. This study was conducted to assess the prevalence of OBI using total anti-HBc by ELISA and DNA detection by real time polymerase chain reaction (PCR). The samples included were negative for HBs Ag by ELISA. Out of 1102 samples tested, 156 were positive for total anti-hepatitis B core antigen and 52/156 by real-time PCR. Overall, the prevalence was found to be 4.71% (52/1102). The results indicate that nucleic acid-based testing should be an essential part of screening procedure to prevent missing of OBI., Competing Interests: There are no conflicts of interest

The implementation of nucleic acid testing in donor screening has improved the safety of tissue allografts. Although infectious disease transmission can be considered a rare event, the detection of occult hepatitis B infection remains challenging. The studies concerning this risk are mainly based on testing blood specimens. This work shows the correlation between results of samples obtained from donor blood and the corresponding tissue washing solution. Hepatitis B virus deoxyribonucleic acid was detected both in bone allografts from donors with serological profiles associated to active hepatitis B infection and occult hepatitis B infection. These results suggest that hepatitis B virus seems to concentrate in bone marrow even when a low viral load is present in peripheral blood. Even detection at molecular level is not enough to avoid the risk of hepatitis B virus transmission and a multiparametrical evaluation is required in tissue donor screening. The role of clinicians in recognition and reporting of allograft-associated infections is a major concern for the acquisition of experience to be applied in risk control of disease transmission.

Aim: To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt., Methods: Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed., Results: HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones., Conclusion: Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA., Competing Interests: Conflict-of-interest statement: Authors do not have any financial or personal relationship with other people or organizations that could inappropriately influence their work.

Purpose: Occult hepatitis B infection (OBI) among HIV positive patients varies widely in different geographic regions. We undertook a study to determine the prevalence of occult hepatitis B infection among HIV infected individuals visiting a health facility in South West Cameroon and characterized occult HBV strains based on sequence analyses., Methods: Plasma samples (n = 337), which previously tested negative for hepatitis B surface antigen (HBsAg), were screened for antibodies against hepatitis B core (anti-HBc) and surface (anti-HBs) antigens followed by DNA extraction. A 366 bp region covering the overlapping surface/polymerase gene of HBV was then amplified in a nested PCR and the amplicons sequenced using Sanger sequencing. The resulting sequences were then analyzed for genotypes and for escape and drug resistance mutations., Results: Twenty samples were HBV DNA positive and were classified as OBI giving a prevalence of 5.9%. Out of these, 9 (45%) were anti-HBs positive, while 10 (52.6%) were anti-HBc positive. Additionally, 2 had dual anti-HBs and anti-HBc reactivity, while 6 had no detectable HBV antibodies. Out of the ten samples that were successfully sequenced, nine were classified as genotype E and one as genotype A. Three sequences possessed mutations associated with lamivudine resistance. We detected a number of mutations within the major hydrophilic region of the surface gene where most immune escape mutations occur., Conclusions: Findings from this study show the presence of hepatitis B in patients without any of the HBV serological markers. Further prospective studies are required to determine the risk factors and markers of OBI.

Occult hepatitis B virus infection (OBI) is characterized by the absence of HBsAg and persistence of the virus genome (HBV-DNA) in liver tissue and/or blood. OBI has been reported in several clinical contexts. However, the clinical significance of OBI in tuberculosis (TB) treatment is unknown. We investigated the OBI prevalence and its impact on the risk of drug-induced liver injury (DILI) during TB treatment. This was a prospective cohort study with one hundred patients who were treated for TB from 2008 to 2015. Laboratory, clinical and demographic data of TB patients were extracted from medical records. Based on HBV-DNA testing of serum samples, an OBI prevalence of 12% was established; almost half of these patients had both anti-HBc and anti-HBs serological markers. Low CD4 + cell counts have been shown to be a risk factor for OBI among TB patients co-infected with HIV (P=.036). High DILI incidence was observed in this study. A multivariable Cox proportional hazard model was conducted and identified OBI (HR 2.98, 95% CI 1.30-6.86) as the strongest predictor for DILI when adjusted to CD4 + cell count (HR 0.38, 95% CI 0.17-0.90), ALT before TB treatment (HR 1.37, 95% CI 0.81-2.32) and TB extrapulmonary clinical form (HR 2.91, 95% CI 1.75-7.21). The main aim of this study was to highlight DILI as a clinical outcome during treatment of TB patients with OBI. Therefore, HBV-DNA testing should be considered routinely in monitoring DILI, and also in other clinical implications associated with OBI, reduce morbidity and mortality., (© 2016 John Wiley & Sons Ltd.)

The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world., Competing Interests: Conflict-of-interest statement: The author declares that there are no conflicts of interest in the content of this review.

Background: Occult hepatitis B infections are becoming a major global threat, but the available data on its prevalence in various parts of the world are often divergent., Objective: This study aimed to detect occult hepatitis B virus in hepatitis B surface antigen-negative serum using anti-HBc as a marker of previous infection., Patient and Methods: A total of 1000 randomly selected hepatitis B surface antigen-negative sera from blood donors were tested for hepatitis B core antibody and hepatitis B surface antibody using an ELISA and nested polymerase chain reaction was done using primers specific to the surface gene (S-gene)., Results: Of the 1000 samples 55 (5.5%) were found to be reactive, of which 87.3% (48/55) were positive for hepatitis B surface antibody, indicating immunity as a result of previous infection however, that does not exclude active infection with escaped mutant HBV. Nested PCR results showed the presence of hepatitis B viral DNA in all the 55 samples that were positive for core protein, which is in agreement with the hepatitis B surface antibody result., Conclusion: This study reveals the 5.5% prevalence of occult hepatitis B among Malaysian blood donors as well as the reliability of using hepatitis B core antibody in screening for occult hepatitis B infection in low endemic, low socioeconomic settings.

Background: Hepatitis B (HB) is a vaccine-preventable liver disease caused by infection with the blood-borne hepatitis B virus (HBV). South African healthcare workers (HCWs) may be at high risk of occupational exposure to HBV infection, since previous studies have found suboptimal levels of protection against HBV in HCWs., Methods: A descriptive prevalence study based on self-administered questionnaires with data on demographics and HB vaccination status, and stored serum samples collected from 2009 to 2012, from 333 HCWs working or studying in Gauteng and Mpumalanga province hospitals or nursing colleges, was conducted. Samples were tested for HB surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to HB core antigen (anti-HBc), and HBV deoxyribonucleic acid (DNA)., Results: The majority of HCWs from whom the serum samples were drawn were black (91.4% [298/326]), female (82.6% [275/333]) and had received at least one dose of HB vaccine (70.9% [236/333]). The average age was 38.8years (range: 19-62). Of the HCWs, 23.2% (73/314) were susceptible (negative for all markers); 9.6% (30/314) were infected (HBsAg and/or DNA positive); 29.0% (91/314) were exposed (positive for either HBsAg, anti-HBc, or DNA); 18.8% (59/314) were immune due to natural infection (anti-HBs and anti-HBc positive only); while 47.8% (150/314) were immune due to vaccination (anti-HBs positive only). Furthermore, HBV DNA was detected in 8.6% (27/314) and occult HBV infection (OBI) (HBV DNA positive but HBsAg negative) was found in 6.7% (21/314) of samples., Discussion and Conclusion: This study, which is the first to report OBI in South African HCWs, found high rates of active HBV infection and sub-optimal protection against HBV in HCWs. There is a need to strengthen vaccination programmes through a policy that ensures protection for all HCWs and their patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B (CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBeAg seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma (HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been (pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosis-induced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

Background: To study the prevalence of occult hepatitis B virus infection (OBI) in a tertiary care hospital., Methods: 50 HBsAg negative individuals, each amongst blood donors, alcohol dependence syndrome (ADS), alcoholic cirrhotics, hepatitis C virus (HCV)/cryptogenic cirrhotics, end-stage renal disease (ESRD) on maintenance haemodialysis for one year, all malignancies prior to chemotherapy and HIV positive patients were evaluated for anti-HBc total antibody, and blood hepatitis B virus (HBV) DNA amplification in those tested positive., Results: A total of 60/369 (16.2%) individuals were anti-HBc total positive, 13/50 (26%) of HCV/cryptogenic cirrhotics, 13/52 (25%) of HIV positive, 10/50 (20%) of patients with malignancy, 10/51 (19.6%) and 7/59 (11.9%) of alcoholic cirrhotics and ADS respectively had intermediate prevalence, while, blood donors 5/55 (9.1%), ESRD patients 2/52 (3.8%) had low prevalence. 12 patients (20% of all anti-HBc total positive cases) were HBV DNA positive, 5 HCV cirrhotics (10% of total HCV/cryptogenic), 4 HIV positive (7.69%), 1 each of ADS (1.69%), alcoholic cirrhotics (1.96%) and malignancy group (2%). Blood donors and ESRD patients were negative for HBV DNA., Conclusion: HBV DNA amplification may under diagnose OBI and anti-HBc total positivity may be a better surrogate marker. Nucleic acid testing of blood donors, however is preferred, especially in high endemic areas. OBI must be looked for in cirrhotics, HIV infection, and patients with cancers prior to chemotherapy, as they may contribute to morbidity in them.

In a previous study, we observed immunoprophylaxis failure due to occult hepatitis B virus (HBV) infection (OBI) despite the presence of adequate levels of anti-HBs in 21 (28%) of 75 children born to HBsAg-positive mothers. The aim of the study was to explore the maintenance of this cryptic condition in this population. Of 21 OBI-positive children, 17 were enrolled. HBV serological profiles were determined by enzyme-linked immunosorbent assay. Highly sensitive real-time and standard PCR followed by direct sequencing were applied in positive cases. The mean age (±SD) of studied patients was 6.57 ± 2.75 years. All children still were negative for HBsAg. All but one (94%) were negative for HBV DNA. Only two children were positive for anti-HBc. The results of the most recent anti-HBs titration showed that 4 (23.5%) and 13 (76.5%) had low (<10 IU/mL) and adequate (>10 IU/mL) levels of anti-HBs, respectively. The only still OBI-positive patient had an HBV DNA level of 50 copy/mL, carried the G145R mutation when tested in 2009 and again in 2013 in the 'a' determinant region of the surface protein. Further follow-up showed that after 18 months, he was negative for HBV DNA. In high-risk children, the initial HBV DNA positivity early in the life (vertical infection) does not necessarily indicate a prolonged persistence of HBV DNA (occult infection). Adequate levels of anti-HBs after vaccine and hepatitis B immune globulin immunoprophylaxis following birth could eventually clear the virus as time goes by. Periodic monitoring of these children at certain time intervals is highly recommended., (© 2015 John Wiley & Sons Ltd.)

We studied the intrahepatic hepatitis B virus (HBV) replicative status in 40 people with occult hepatitis B infection (OBI) and 40 patients with chronic hepatitis B (CHB). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pre-genomic RNA (pgRNA) were quantified. Patients with OBI had median necroinflammation and fibrosis scores of 1 and 0, respectively. Intrahepatic total HBV DNA, cccDNA and pgRNA were detectable in 30 (77%), one (3%) and five (13%) of the participants with OBI, respectively. People with OBI had lower median intrahepatic total HBV DNA than the patients with CHB (p < 0.0001). They had nearly normal liver histology and low intrahepatic HBV replication., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Transfusion-transmitted infections including hepatitis B virus (HBV) have been a major concern in transfusion medicine. Implementation of HBV nucleic acid testing (NAT) has revealed occult HBV infection (OBI) in blood donors. In the mid-1980s, hepatitis B core antibody (HBc) testing was introduced to screen blood donors in HBV non-endemic countries to prevent transmission of non-A and non-B hepatitis. That test remains in use for preventing of potential transmission of HBV from hepatitis B surface antigen (HBsAg)-negative blood donors, even though anti-hepatitis C virus tests have been introduced. Studies of anti-HBc-positive donors have revealed an HBV DNA positivity rate of 0%-15%. As of 2012, 30 countries have implemented HBV NAT. The prevalence of OBI in blood donors was estimated to be 8.55 per 1 million donations, according to a 2008 international survey. OBI is transmissible by blood transfusion. The clinical outcome of occult HBV transmission primarily depends on recipient immune status and the number of HBV DNA copies present in the blood products. The presence of donor anti-HBs reduces the risk of HBV infection by approximately five-fold. The risk of HBV transmission may be lower in endemic areas than in non-endemic areas, because most recipients have already been exposed to HBV. Blood safety for HBV, including OBI, has substantially improved, but the possibility for OBI transmission remains.

Objectives: Health care workers, including dentists, are at the front line for acquiring blood-borne virus infections. This study aimed to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency viruses among Iranian dentists., Material and Methods: The survey included 1628 dental health care workers who attended the 51st annual Congress of the Iranian Dental Association. Data on the risk of blood-borne virus transmission during health care and infection control practices were gathered from self-administered questionnaires. Sera were screened serologically by enzyme-linked immunosorbent assay (ELISA). The positive samples were examined by polymerase chain reaction (PRC) followed by direct sequencing., Results: Six (0.36%) and 81 (5.0%) were positive for hepatitis B surface antigen (HBsAg) and (anti-hepatitis B virus core antigen (anti-HBc), respectively. Only 1 (0.061%) was positive for anti-hepatitis C virus (anti-HCV). No case was positive for anti-human immunodeficiency virus (anti-HIV). One case was diagnosed as being occult hepatitis B virus (HBV) infection. One thousand five hundred thirty-five (94.3%) of participants had received at least 1 dose of HBV vaccine. One thousand three hundred fifty-nine (88.5%) contained hepatitis B surface antibody (anti-HBs) > 10 IU/ml, of whom 55 (4.0%) were anti-HBc positive, suggesting that they had been infected with HBV in the past. Anti-HBc positive cases had past histories of hepatitis, either their own or their spouses'. Individuals with inadequate anti-HBs levels (< 10 IU/ml) were significantly more prevalent among anti-HBc positive cases (p < 0.001)., Conclusions: The prevalence of blood-borne viruses among dental HCWs found in this study was lower than past reports from Iranian dentists and general population. The implementation of HBV vaccination together with improvement in infection control procedures has reduced the potential for risk infection among Iranian dentists., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Aim: We tried to characterize the pathological features of patients who developed hepatocellular carcinoma (HCC) with the negative results of both serous hepatitis B surface antigen and hepatitis C virus antibody (non-B, non-C)., Methods: In a multicenter study in Kyushu, Japan, we studied the histopathological characteristics of non-cancerous liver tissues in 129 patients (103 men and 26 women) with non-B, non-C HCC. The histological liver damage was evaluated for fibrosis (stage) and inflammation (grade) according to the Ludwig classification of chronic hepatitis. In addition, we examined the hepatitis B virus (HBV) genome in serum samples and liver tissues of 20 patients with non-B, non-C HCC., Results: Positivity of serum hepatitis B core (HBc) antibody, alcohol abuse, diabetes and non-alcoholic steatohepatitis were present in 61 (47%), 76 (59%), 57 (44%) and eight (6%) patients, respectively. The degree of fibrosis was mild (stage 1.6 ± 1.2). The stage of patients with neither serum HBc antibody nor alcohol abuse was significantly lower than the stage of patients with HBc antibody and no alcohol abuse (P < 0.05). HBV genome was detected in 15 cancerous tissues (75%) and 16 non-cancerous liver tissues (80%) in 20 patients with non-B, non-C HCC. Only three of the 20 patients were positive for serum HBc antibody., Conclusion: Non-B, non-C patients appear to develop HCC at a low stage of fibrosis. Occult hepatitis B virus infection is the major risk factor for HCC of non-B, non-C patients in Kyushu, Japan., (© 2013 The Japan Society of Hepatology.)

Aim: To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection., Methods: The clinical and laboratory data of children who underwent LDLT from June 2010 to September 2012 in First Center Hospital in Tianjin, China, were retrospectively included in the study. Intrahepatic HBV DNA in donors and recipients was quantified by real-time polymerase chain reaction using DNA extracted from formalin-fixed, paraffin-embedded tissues., Results: Between June 2010 to September 2012, 32 consecutive pediatric patients underwent LDLT in our institute. Thirty LDLT patients (13 girls and 17 boys) were followed up for a median of 15 mo, of whom 53.3% (16/30) were hepatitis B core antibody (HBcAb) positive and 36.7% (11/30) were hepatitis B surface antibody (HBsAb)/HBcAb positive before transplantation. Sixteen of the children received HBcAb-positive allografts, and 43.7% (7/16) of the grafts were found to be intrahepatic HBV DNA positive. De novo HBV infection developed in 16.1% (5/30) of the children within a median of 11 mo after transplantation. All five of the HBV-infected children had received HBcAb-positive allografts, four of which were intrahepatic HBV DNA positive. Two of the children developed de novo HBV infection despite the preoperative presence of both HBsAb and HBcAb, Conclusion: In pediatric recipients, positive intrahepatic HBV DNA in allografts could be a risk factor for de novo HBV infection from HBcAb-positive allografts. HBsAb/HBcAb positivity in pediatric LDLT patients before transplantation exhibited only weak effectiveness in protecting them against de novo HBV infection from HBcAb-positive allografts.

Objectives: The aims of this study are to investigate the prevalence of occult hepatitis B virus infection among patients with cryptogenic cirrhosis and to analyze the relationship between surface protein variability and occult hepatitis B virus infection, which may be related to the pathogenesis of occult hepatitis B virus infection in cryptogenic cirrhosis. Occult hepatitis B virus infection is a well-recognized clinical entity characterized by the detection of hepatitis B virus DNA in serum and/or liver in the absence of detectable hepatitis B virus surface antigen, with or without any serological markers of a past infection., Methods: Sera from patients with cryptogenic chronic liver disease were tested for hepatitis B virus DNA using both real-time and nested PCR. In the detected hepatitis B virus DNA samples, the surface gene was analyzed for mutations., Results: Hepatitis B virus DNA was detected in 38% of patients, all of whom had a viral load below 10,000 copies/mL. All hepatitis B virus belonged to genotype D. There were no significant associations between occult hepatitis B virus infection status and age, gender, ALT/AST levels, viral load or serologic markers of previous hepatitis B virus infection. There were 14 mutations found in 5 patients; 6 were in the major hydrophilic region, of which 4 were Y134F assigning for the "a" determinant region. All patients who acquired Y134F contained S207R (within HLA-A2-restricted CTL epitope) as a combination., Conclusion: Hepatitis B virus surface antigen variants may arise as a result of natural selection to evade the immune surveillance of the infected host, and subsequently may go undetected by conventional hepatitis B virus surface antigen screening tests. Etiological diagnosis of cryptogenic cirrhosis is significantly underestimated with current serology testing methods alone.

Background and Objectives: In Lao People's Democratic Republic, hepatitis B virus is highly endemic. However, blood donations are only screened for HBsAg, leaving a risk of transmission by HBsAg-negative occult infected donors. Here, we characterized first-time blood donors to assess prevalence of hepatitis B virus infections and occult infected donors., Materials and Methods: Sera were screened for HBsAg, HBeAg and anti-HBs, anti-HBc and anti-HBe antibodies. Occult HBV infections (OBIs) were assessed in HBsAg-negative sera by PCR, and sera of HBsAg positive and occult infected donors were phylogenetically characterized., Results: 9·6% of the donors were HBsAg positive, and 45.5% were positive for at least one of the hepatitis B virus serum markers. More than 40% HBsAg carriers were HBeAg positive, with HBeAg seroconversion occurring around 30 years of age. Furthermore, 10·9% of HBsAg-negative, anti-HBc and/or anti-HBs-positive donors were occult infected with hepatitis B virus. Thus, at least 3·9% of blood donations would potentially be unsafe, but hepatitis B virus DNA copy numbers greatly varied between donors., Conclusion: In Lao People's Democratic Republic, a sizable proportion of HBsAg-negative and anti-HBc antibody-positive blood donations are potentially DNA positive and infective for hepatitis B., (© 2013 International Society of Blood Transfusion.)

Occult hepatitis B infection (OBI) is defined as long-lasting persistence of hepatitis B virus (HBV) DNA in the liver of patients with hepatitis B surface antigen (HBsAg)-negative status, with or without serological markers of previous exposure (antibodies to HBsAg and/or to hepatitis B core antigen). Over the past two decades, significant progress has been made in understanding OBI and its clinical implications. OBI as a cause of chronic liver disease in patients with HBsAg-negative status is becoming an important disease entity. In conditions of immunocompetence, OBI is inoffensive in itself and detection of HBV DNA in the liver does not always indicate active hepatitis. However, when other factors that cause liver damage, such as hepatitis C virus infection, obesity and alcohol abuse are present, the minimal lesions produced by the immunological response to OBI might worsen the clinical course of the underlying liver disease. Several lines of evidence suggest that OBI is associated with progression of liver fibrosis and the development of hepatocellular carcinoma in patients with chronic liver disease. The major interest in OBI is primarily associated with the growing, widely discussed evidence of its clinical impact. The aim of this review is to highlight recent data for OBI, with a major focus on disease progression or carcinogenesis in patients with chronic liver disease.

Persistence of hepatitis B virus-DNA in the sera, peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen (HBsAg)-negative patients with or without serological markers of previous exposure (antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection (OBI). Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas. While this co-infection increases the risk of liver disease progression, development of cirrhosis and hepatocellular carcinoma and also increases the rate of therapeutic failure to interferon-based treatments than either virus alone, a potentially negative effect of OBI on clinical outcomes and of therapeutic response to current antiviral regimes of patients with chronic hepatitis C remains inconclusive.

Background and Aims: Occult hepatitis B infected (OBI) patients can not completely eradicate hepatitis B virus-DNA (HBV-DNA) from their liver and peripheral blood. The main aim of this study was to investigate the Interleukin (IL)-10and IL-17A serum levels in patients suffering from OBI., Material and Methods: In this observational study, plasma samples of 3700 blood donors were tested for hepatitis Bsurface antigen (HBsAg) and antibodies to the hepatitis B core antigen (anti-HBc), using enzyme-linked immunosorbent assay (ELISA). The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA, using the polymerase chain reaction (PCR). HBV-DNA positive samples were assigned as OBI cases and IL-10 and IL-17 serum levels were detected using ELISA., Results: The results demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of the HBsAg-/anti-HBc+ samples. Our results showed that the IL-10 and IL-17A serum levels increased significantly in the OBI cases in comparison to the controls (P < 0.001)., Conclusions: According to the results of this study the higher level of IL-10 production may suppress the functioning of the immune system against HBV in OBI patients. The elevated IL-17A serum level also indicates a long period of infection in the patients observed.