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BACKGROUND: People living with HIV (PLHIV) may have concurrent Hepatitis B Virus (HBV) infection, and certain antiretroviral therapies are recommended for HBV-HIV co-infected individuals. Routine screening for Hepatitis B virus may influence management of antiretroviral therapy for PLHIV, but risk factors for co-infection have not been well defined. The objective of this study was to identify risk factors for HBV infection among PLHIV in South Africa. METHODS: We conducted a cross-sectional analysis of a prospective, clinic-based cohort study of adults seeking HIV testing from 2013-2017 in Umlazi township, South Africa. Patients newly diagnosed with HIV were enrolled and subsequently tested for Hepatitis B surface antigen positive (HBsAg +). We used a Poisson linear regression model to assess which factors, pertaining to sociodemographic status, medical history, clinical symptoms, mental health were associated with HBV. RESULTS: Among 3,105 PLHIV participants in South Africa, 6% were positive for HBV. Males had a higher HBV prevalence (10.4%) than females (5.2%). Within the HBV-positive group, the mean age was 33.2 years, with 38.3% females and 43.9% having completed high school or higher. About 39.9% reported alcohol use, 24.7% had a smoking history, and 8.3% reported substance use in the past year. Older participants born before 1995, when routine infant HBV vaccination was introduced, were more likely to have HBV. In multivariable analyses, smoking history increased HBV risk in females (aPR = 2.58; 95% CI 1.47-2.52), while alcohol use decreased HBV risk in males (aPR = 0.36; 95% CI 0.19-0.70). CONCLUSIONS: In a South African cohort, roughly one in 16 PLHIV had HBV co-infection, and this rate was higher in males. The most prominent risk factors for HBV infection in PLHIV were alcohol use, higher income, and smoking history, which may help inform targeted treatment and prevention strategies. Creating HBV-specific screening and prevention strategies for PLHIV may be useful for reducing HBV infections.

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

ABSTRACT Background and Aims Methods Results Conclusions To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.The annual incidence of HCC was 2.1/100 person‐years after a follow‐up period of over 4840.5 person‐years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55–5.81; p = 0.001), male sex (2.98/1.51–5.90; p = 0.02), body mass index (1.11/1.04–1.18; p = 0.002) and age (1.06/1.04–1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00–4.25; p = 0.04) and NO2 (per one‐unit increment, parts per billion; 1.07/1.01–1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three‐fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34–7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79–19.23; p = 0.004), age (1.12/1.07–1.17; p < 0.001) and platelet count (0.99/0.98–1.00; p = 0.04).Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long‐term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment. [ABSTRACT FROM AUTHOR]

Introduction. Blood-borne infections are a serious problem among medical staff, especially nursing staff, because nurses have the most frequent contact with patients. As future employees of health care, students of nursing are exposed to a number of hazardous factors. Work with patients of unknown serological status (during practical classes and apprenticeships) is associated with the risk of infection with various pathogens. Objective. The aim of the study was recognition of the level of knowledge concerning prevention of blood-borne infectious diseases among Master's degree students of nursing. Material and Methods. The study was conducted in the second half of 2022 among 104 Master's degree students of nursing, who were educated at the Radom School in Radom, by the method of a diagnostic survey, using an author-constructed questionnaire. Results. The majority of the examined students (96.2%) knew what diseases are transmitted through blood. More than a half of respondents (63.5%) evaluated their level of knowledge about blood-borne diseases as mediocre, and 19.2% - as low. A part of respondents (67.3%) had knowledge that trace amounts of blood are enough to cause infection with blood-borne diseases. All students in the study knew the main methods of prevention of infections transmitted via blood, and the deficit of knowledge concerned proper use of personal protection equipment (5.8%) and the observance of the procedure to be followed in the event of occupational exposure (3.8%). A large group of respondents (82.7%-100.0%) knew various risk factors of infection with blood-borne diseases. The majority of respondents (88.5%) knew that there is an effective vaccine against hepatitis B, but 43.3% of the students in the study did not know the main symptoms of infection with HBV. Students most often knew (90.4%) how to diagnose infection with HCV - anti-HCV test for the presence of antibodies against hepatitis C virus in blood; however, 26.9% of respondents were not aware that there is no vaccine against hepatitis C. The majority of the examined students (84.7%) knew early symptoms of infection with HIV, while the remainder had a deficit of knowledge in this area. A large group of respondents (82.0%-94.0%) knew various risk factors of infection with HIV. Conclusions. Students of nursing should be motivated to expand their knowledge concerning prevention of blood-borne diseases, observance of the principles of personal protection, prevention of occupational exposure, and proper post-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

An effective vaccine against hepatitis C virus (HCV) should elicit both humoral and cellular immune responses. Previously, we characterized a bivalent vaccine candidate against hepatitis B (HBV) and HCV using chimeric HBV-HCV virus-like particles (VLP), in which the highly conserved epitope of HCV E2 glycoprotein (residues 412–425) was inserted into the hydrophilic loop of HBV small surface antigen (sHBsAg). While sHBsAg_412–425 elicited cross-neutralizing antibodies, it did not trigger a T-cell response against HCV. Thus, this study aimed to develop a vaccine candidate engaging both arms of adaptive immune response, potentially offering stronger protection against HCV. We evaluated the immunogenicity of minicircle (MC) DNA vaccines encoding sHBsAg_412–425 and HCV nonstructural (NS) proteins in BALB/c mice. Co-administration of sHBsAg_412–425 and NS induced a potent T-cell response, especially against NS3 and high titers of antibodies specific to HCV E2. Additionally, these antibodies recognized native HCV envelope glycoprotein heterodimers (E1E2) across multiple HCV genotypes and showed binding profiles to E1E2 alanine mutants comparable to the broadly neutralizing AP33 antibody. Overall, the findings demonstrate that MC DNA vaccine incorporating both sHBsAg_412–425 and HCV NS protein sequences induces robust, T-cell and AP33-like antibody responses, highlighting its potential as pan-genotypic prophylactic vaccine against HCV. [ABSTRACT FROM AUTHOR]

Background: Nigeria remains one of the countries with a high hepatitis B virus (HBV) burden in Africa. Reports have indicated the presence of mixed HBV genotypes in Nigeria; however, there is still paucity of data regarding mixed genotype infections particularly in the Southern part of the country. Objective: Our aim is to determine the HBV genotype distribution among HBsAg-positive gastroenterology patients at the University College Hospital Ibadan, Nigeria. Method: Serum samples were screened for HBsAg by ELISA, and positive samples were genotyped by semi-nested multiplex PCR for HBV genotypes A, B, C, D, E and F. Results: Data generated were analyzed in R-studio. A total of 81/90 (90%) of HBsAg-positive samples were successfully genotyped, and genotype A was most prevalent with 15.7%, while genotypes B and E were the least with 1.2% each. Genotypes A/C infection was the highest among mixed infections with 40% prevalence, while genotypes A/D were the least prevalent mixed infection with 4.8%. Conclusion: We advocate for a comprehensive genotype analysis in larger cohorts across Nigeria, to give a more comprehensive understanding of the distribution and prevalence of different HBV genotypes population wide. [ABSTRACT FROM AUTHOR]

Background and Objectives: South Africa has a high prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and to a lesser extent human T‐lymphotropic virus (HTLV). Each of these agents is transfusion‐transmissible (TT) but deciding whether to implement preventive screening depends upon knowledge of background prevalence in transfused patients. We determined the prevalence of HIV, HBV and HTLV I/II among blood transfusion recipients in South African hospitals. Materials and Methods: We obtained identity‐unlinked samples used for blood cross‐matching at 634 South African hospitals served by the South African National Blood Service (SANBS). The ABBOTT Alinity S® Immunochemiluminescent system measured HIV, HBV and HTLV I/II antibodies. Repeatedly reactive samples were confirmed using the Roche Cobas® 8000. Logistic regression was performed to investigate the determinants of associations for HIV, HBV and HTLV infections. Results: The overall prevalences of HIV, HBV and HTLV were 37.8%, 7.4% and 0.6%, respectively. The HIV prevalence in blood recipients was twice as high as general population estimates. Public hospital patients had a significantly higher prevalence compared with private hospital patients for HIV and HBV. HIV prevalence was significantly higher in females, and HBV prevalence was significantly higher in males, excluding the unknown gender results. Conclusion: Patients receiving blood transfusions in South Africa have high rates of HIV and HBV infection that should be taken into consideration when determining donor screening strategies for other viral infections. Measurable prevalence of HTLV indicates endemicity of this infection in South Africa. [ABSTRACT FROM AUTHOR]

Background and Objectives: In 2016, France allowed men who have sex with men (MSM) to donate blood if they had not had sex with men in the previous 12 months. In April 2020, this restriction was relaxed to 4 months due to the lack of negative impact observed on blood safety. This study assesses the impact of reducing this deferral period on epidemiological surveillance indicators. Materials and Methods: This study compares infection surveillance indicators between two 30‐month periods before (P1) and after (P2) this second deferral change. Results: Overall, 79 donations tested positive for human immunodeficiency virus (HIV) (49 in P1 and 30 in P2), 322 for hepatitis C virus (HCV) (185 and 137), 622 for hepatitis B virus (HBV) (355 and 267) and 1684 for syphilis (799 and 885). Positive donation rates decreased between P1 and P2, except for syphilis: HIV (0.07/10,000 donations vs. 0.04; p > 0.5), HCV (0.25 vs. 0.20; p < 0.05), HBV (0.49 vs. 0.39; p < 0.01) and syphilis (1.10 vs. 1.29; p < 0.001). For all three viruses, residual risks of transmission by transfusion did not increase: HIV (1/7,800,000 donations vs. 1/10,500,000), HCV (1/25,200,000 vs. 1/47,300,000) and HBV (1/6,400,000 vs. 1/6,000,000). Conclusion: Reducing the deferral period for MSM in April 2020 did not negatively impact residual risks, which remained very low, or the rate of positive donations, except for syphilis, which requires careful monitoring. To ensure equal access to blood donation, MSM have been allowed to donate blood under the same conditions as other donors since March 2022 (i.e., no more than one sexual partner in the last 4 months). [ABSTRACT FROM AUTHOR]

Chronic Hepatitis B Virus (HBV) infection remains a significant public health concern, particularly in Africa, where the burden is substantial. HBV is an enveloped virus, classified into ten phylogenetically distinct genotypes (A–J). Tests to determine HBV genotypes are based on full-genome sequencing or reverse hybridization. In practice, both approaches have limitations. Whereas diagnostic sequencing, generally using the Sanger approach, tends to focus only on the S-gene and yields little or no information on intra-patient HBV genetic diversity, reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV diagnostic sequencing protocol suitable for clinical virology that yields both complete genome sequences and extensive intra-patient HBV diversity data. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit (Oxford nanopore Technologies, Oxford, OX4 4DQ, UK), ONT GridION sequencing, genotyping using genome detective software v1.132/1.133, a recombination analysis using jpHMM (26 October 2011 version) and RDP5.61 software, and drug resistance profiling using Geno2pheno v2.0 software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 residual diagnostic samples from HBV-infected patients in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world. [ABSTRACT FROM AUTHOR]

Background: Globally, sexually transmitted infections (STIs) collectively cause 2.3 million deaths and 1.2 million cases of cancer annually. However, the epidemiology of STIs in the Middle East and North Africa (MENA) is not well assessed because of various social and cultural factors. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and covering 23 MENA countries, 19 STIs, and data from 20,435,971 participants. PubMed, Embase, regional and international databases, and country-level reports were searched up to May 2024. Results: The analysis revealed significant regional variations in the prevalence of STIs within the MENA region. In North Africa, the most common STIs were bacterial vaginosis (31%), human papillomavirus (HPV, 23%), and Candida spp. (15%). In the Gulf Cooperation Council region and Yemen, Ureaplasma (25%), nongonococcal urethritis (NGU, 16%), and Mycoplasma spp. (12%) were the predominant infections. In the Levant region, the top STIs were HPV (20%), hepatitis B virus (HBV, 9%), and Candida spp. (9%). In Iran, Ureaplasma spp. (18%), HPV (17%), and cytomegalovirus (8%) were the most prevalent infections, whereas Ureaplasma spp. (20%), Candida spp. (18%), and HPV (16%) were most frequently detected in Türkiye. Gender-based disparities were observed, with a higher prevalence of Ureaplasma spp., Neisseria gonorrhoeae, and herpes in men and higher rates of Mycoplasma spp., HPV, HBV, and Candida spp. in women. Overall, high rates of nongonococcal urethritis (16.3%), Ureaplasma spp. (13.7%), HPV (12.7%), and Candida spp. (9.4%) were recorded in the MENA region. Conclusions: Most MENA countries lack national STI screening programs, and the reported data are primarily from symptomatic individuals. Establishing robust surveillance systems, addressing stigma and barriers to healthcare access, and expanding STIs screening and vaccination programs are crucial for accurately capturing the true burden of STIs in MENA countries. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) leads to liver inflammation and dysfunction, resulting in liver fibrosis and cancer. Nucleos(t)ide analogues (NAs), inhibitors of hepatitis B virus (HBV), specifically suppress HBV replication. We proposed that immune modulation benefits seroconversion by HBsAg loss. However, activation of T lymphocytes also deteriorates hepatic inflammation. Therefore, we intended to investigate the T cell status and its relationship with hepatic functions in CHB patients treated with NAs. Serum markers, including liver function markers AST, ALT, and HBV-infected markers HBV DNA, HBsAg, HBeAg, and HBsAb were measured in the clinical routine. The T cell levels and markers, including CD69, CD107a, CXCR3, and PD-1 were investigated using flow cytometry. Meanwhile, IFNγ, IL-2, and CXCL10 as immune activation markers in the PBMCs were investigated using qPCR. To validate the effects of NAs on T cell status, qPCR and flow cytometry were used to investigate the gene expression in the HepG2 and PLC5 cells treated with NAs, and in the healthy PBMCs treated with the cell-cultured supernatant. We found that NAs significantly suppressed HBV DNA and reduced AST and ALT levels in the CHB patients. Meanwhile, AST and ALT were both positively correlated with activation marker CD107a in CD8+ T cells. In addition, we found that the CHB patients with seroconversion exhibited a higher CD4/CD8 ratio (p < 0.05) compared to non-seroconversion. We demonstrated that NAs potentially induced IFNs and PD-L1 expression in HepG2 and PLC5 cells. Moreover, the collected supernatant from NAs-treated HepG2 significantly activated PBMCs. This study revealed that the reduction of HBV by NAs may be the reason leading to less AST and ALT levels. We further demonstrated that NAs induced IFN expression in hepatic cells to potentially activate T lymphocytes, which was positively associated with AST and ALT levels in the CHB patients. The results may explain the phenomena in clinical that when the virus is reactivated by aborted use of NAs, it causes consequent T cells-mediated severe acute-on-chronic liver injury. [ABSTRACT FROM AUTHOR]

Background: The burden of chronic viral hepatitis among people living with human immunodeficiency virus (PLWH) and its association with liver disease in Nigeria has been seldom explored. Our objective was to compare characteristics in PLWH with and without significant liver fibrosis/cirrhosis, examining its association with viral hepatitis and other risk factors. Methods: Cross-sectional study among PLWH with and without significant fibrosis/cirrhosis (transient elastography ≥ 9.3 kPa) between July 2018 and August 2022. Data were compared between participant groups and logistic regression used to determine association between chronic viral hepatitis and significant fibrosis/cirrhosis. Results: Five hundred and thirty-seven participants (34.3% male), median age 46 years, 22.2% with significant fibrosis/cirrhosis were analyzed. Seroprevalence of hepatitis B virus (HBV) was 11.2% and hepatitis C virus (HCV) 5.7%. Male sex, diabetes, HBV, and HCV were associated with significant fibrosis/cirrhosis, while ART for >5 years was associated with reduced risk. Conclusion: The chronic hepatitis viruses are associated with significant liver fibrosis/cirrhosis in PLWH in Nigeria, highlighting the importance of viral hepatitis awareness, screening, and treatment in HIV programs to reduce the risk of liver disease. Plain Language Summary: Hepatitis B and C infection and liver disease in people with HIV infection in Nigeria People living with human immunodeficiency virus (HIV) infection who have hepatitis B or C infection have a higher chance of developing advanced liver disease than those who do not have either of the hepatitis infections. This finding highlights the importance of awareness, screening, and treatment of the hepatitis viruses in HIV programs in order to reduce the risk of liver disease in this population. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite the availability of effective treatment and vaccines for hepatitis B virus (HBV) and C virus (HCV), many people are still infected and remain unaware of their infection. The Camden and Islington Viral Hepatitis Identification Tool (CIVHIT), a computer‐based search tool, was introduced in 60 general practices (GPs) in April 2014 to support identification, testing and treatment of individuals at high risk for blood‐borne viruses (BBVs). CIVHIT searched electronic medical records (EMRs), flagging all those with codes linked to risk factors or medical conditions associated with BBVs. CIVHIT was associated with a 78.5% increase in BBV tests in primary care in both boroughs. This translated to a 55.8% rise in new diagnoses. HBV testing saw the largest increase resulting in twice as many people diagnosed. Only 23.2% of HBV and 14.9% of HCV‐positive tests were referred to secondary care. In an index practice, the most common flag was a history of STIs (477/719, 66.3%). Individuals with previous or current drug use and those with a known hepatitis contact were more likely to be offered a test compared to those flagged due to a history of STI. HIV and HBV testing was lower in males following a test offer. There was an increased likelihood of testing for HBV and HCV with increasing age. Additionally, individuals with previous or current drug use and individuals with a known hepatitis contact were more likely to test for HCV compared to individuals flagged due to STI history. CIVHIT shows promise to assist with the elimination of BBVs. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis B virus (HBV) infection is a significant contributor to the development of hepatocellular carcinoma (HCC), a leading cause of cancer‐related mortality worldwide. Iron, a central co‐factor in various metabolic pathways, plays an essential role in liver function, but its dysregulation can lead to severe health consequences. Accumulation of iron within hepatic cells over time is linked to increased liver injury and is strongly associated with sensitive exposure to a range of conditions, including cirrhosis, fibrosis and ultimately, HCC. This review explores the intricate interplay between iron metabolism and HCC within the context of HBV infection. Hepatic iron overload can arise from liver injury and disruptions in iron homeostasis, causing hepatic necrosis, inflammation, and fibrosis, ultimately culminating in carcinogenesis. Moreover, alterations in serum iron components in HBV‐related scenarios have been observed to impact the persistence of HBV infection. Notably, the progression of HBV‐associated liver damage exhibits distinct characteristics at various stages of liver disease. In addition to elucidating the complex relationship between iron metabolism and HCC in the context of HBV infection, this review also investigates the prognostic implications of systemic iron levels for HCC. Furthermore, it aims to provide a comprehensive understanding of the intricate interplay between iron metabolism and HCC, extending the discussion to the context of hepatitis C virus (HCV) infection. By shedding light on these multifaceted connections, this review aims to contribute to our understanding of the pathogenesis of HBV‐associated HCC and potentially identify novel therapeutic avenues for intervention. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a public health concern in resource limited settings like Ghana. Over the past decades, it is noted that the natural course of HBV in persons infected are taking a worse turn leading to liver cirrhosis and cancer. The outcome of HBV infection is influenced by viral and host factors including genetics. Cytokine variations affect virus survival and progression and may even influence associated complications. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (IL-4, IL-6, IL-8, IL-10, IL-18), interferon gamma (IFN)-γ, and tumor growth factor-beta (TGF-β) have key roles in HBV infection and modulation. In this study, polymorphisms occurring in five cytokines were analysed to understand how they can influence prognosis of HBV infection. Methods: The study is a single centre cross-sectional study involving 227 participants made up of HBV infected participants and HBV-negative controls. Recruitment was from March 2021 to April 2022. Blood samples were taken for full blood count, HBV antigen profile, liver function tests, HBV DNA quantification and cytokine genotyping. FIB score was calculated using available tools. Statistical analysis was undertaken with p < 0.05 set as statistically significant. Results: The 20–39-year-old group formed majority of the HBV infected participants with 60% of all participants being classified as healthy HBsAg carriers. IL2 rs1479920 GG carriers ((1258.93; 0.00–5011.87) IU/mL had reduced HBV DNA in comparison to IL2 rs1479920 AA ((5011.87; 2113.49–5956.62) /AG (3548.13; 0.00–6309.57) IU/mL carriers. TNF-α rs1800629 AA carriers (1258.93; 0.00–3981.07) IU/mL had a reduction in HBV DNA levels in comparison to TNF-α rs1800629 GG carriers (1584.89; 0.00–5011.87) IU/mL. The results of univariate (OR = 0.08, 0.00–0.93; p = 0.043) and multivariate (OR = 0.02, 0.00–0.67; p = 0.029) analysis, showed that carrying TNF-α rs1800629 AA genotype reduce susceptibility to high FIB score compared with GG genotypes. In univariate analysis, subjects aged 20–39 years (OR = 5.00, 1.13–6.10; p = 0.034) and 40–59 years (OR = 41.99, 3.74–47.21; p = 0.0002) were more susceptible to high FIB score compared to subjects aged 1–19 years. Being female (OR = 2.42, 1.03–5.71; p = 0.043) in the univariate models showed higher odds of having high levels of HBV DNA in the multivariate model. There was a reduced likelihood of herbal medicine usage influencing HBV DNA levels significantly (OR = 0.29, 0.10–0.86; p = 0.025). Conclusion: In conclusion, variations in IL2 rs1479920 GG and IL2 rs1479921 AA could offer protective effects by reducing HBV DNA. TNF-α rs179924CT may also cause elevation in HBV DNA levels whiles TNF-α -308A/G, showed a potential protective effect on liver scarring in HBV infected participants. It is therefore important to take a further look at such variations for understanding of HBV modulation in the Ghanaian population. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Transfusion‐transmissible infection (TTI) prevalence among US blood donors has been widely documented. Here we estimate the prevalence of donors presenting with ≥2 TTIs (multiple infections past or present referred to as coinfections) and describe their demographics and associations.Data from the Transfusion‐Transmissible Infections Monitoring System were compiled for October 2020–September 2023 (3 years). Prevalence per million donations (pmd) was calculated for each TTI coinfection combination with demographic characteristics summarized. The odds of each TTI coinfection combination were estimated using logistic regression. Reactivity by NAT and/or serology (HIV, HBV, and HCV) defined donors as consensus positive (CP) for each infection while serology‐based algorithms defined syphilis CP and the subset with active syphilis infections (ASIs).About 22 million donations were included, with 212 coinfections (9.7 pmd). Around 2% of donations positive for any TTI (n = 10,516) were coinfections. Coinfection prevalence per TTI combination ranged from 0.3 pmd for HIV CP and HCV CP, to 4.3 pmd for HIV CP and syphilis CP. There were high proportions of coinfections from donors who were male, aged 25–54 years, white or black, first time, and residing in the southern US Census Region. The odds of a second TTI occurring in an individual donor with a TTI ranged from 23 (95% CI: 13, 41) times more likely for HBV CP and ASI to 395 (95% CI: 298, 524) times more likely for HIV CP and ASI.Coinfections are relatively uncommon among blood donors in the United States; however, associations exist among HIV, HBV, HCV, and syphilis infections. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

ABSTRACT Estimates of chronic hepatitis B virus (HBV) prevalence and critically the amount of infection that is undiagnosed or unlinked to care are uncertain—even in countries like UK where vertical transmission and overall prevalence are very low. In the absence of country of birth data, we aim to estimate HBV prevalence through combining public health surveillance data on antenatally screened women by ethnic group and multipliers generated from non‐antenatally screened populations by ethnic group with English population denominators. Of 714,287 women aged 16–49 years with ethnic group data tested as part of antenatal care between 2015 and 2021, 4174 (0.6%) were HBsAg‐positive; 94% in people of ethnic groups other than White British. Of 1,447,467 people tested for HBsAg with ethnic group data from other testing sources (primary and secondary care excluding occupational health and renal services), 27,628 (1.9%) were HBsAg‐positive; 87% in people of ethnic groups other than White British. We estimate that the overall number and prevalence of people with chronic hepatitis B in England is 268,767 (95% CI: 227,896–314,044) and 0.58% (95% CI: 0.50–0.68). Approximately two‐thirds were male, one‐third female, and 68% were aged under 50. We estimate that over 83% of HBV infections are in people of ethnic groups other than White British, with 23% in people from Black ethnic groups, 21% from other White ethnic groups and 19% in Asian ethnic groups. These estimates are the first step towards establishing whether England can meet World Health Organisation targets to eliminate HBV as a public health problem—using methods that can also be used by other countries. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B and C are significant viral infections in pregnancy with high risk of maternal and neonatal complications. This study was conducted to determine the prevalence of hepatitis B and C viral infections and correlates among pregnant women who attended antenatal care (ANC) unit of General and Civil Service Hospitals, Ilorin, Nigeria. Methodology: This was a descriptive cross-sectional study of 282 consented pregnant women randomly selected from the ANC units of two hospitals in Ilorin. Blood samples were collected from the pregnant women and tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-hepatitis C virus (HCV) antibody using Enzyme Linked Immunosorbent Assay (ELISA) technique. Socio-demographic and obstetrics information of the pregnant women and potential risk factors for HBV and HCV infections were collected using a pretested structured questionnaire. Statistical analysis was done using SPSS version 22.0 Results: Majority of the women were married (78.4%), from monogamous families (57.8%), do not share sharp objects (65.6%), have not received blood transfusion (65.3%), have no history of organ transplantation (91.1%), and multigravida (61.4%,) in their first (36.9%), second (37.2%) and third (25.9%) trimesters of pregnancy. Overall, 22.3% and 1.4% tested positive for HBsAg and anti-HCV respectively. Family background of the study participants showed significant (p˂0.05) association with HBsAg positivity. None of the other analysed variables showed any significant association with both HBsAg and anti-HCV positivity. Conclusion: This result showed high prevalence of HBV but low prevalence of HCV infections among pregnant women in the study setting. Improved surveillance and routine screening for HBV and HCV for women attending ANC is recommended to reduce disease burden and help achieve WHO goal of eliminating viral hepatitis as a major public health threat by 2030. [ABSTRACT FROM AUTHOR]

Objectives: CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA‐DR+CD8+ T cells, or bystander‐activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA‐DR+CD8+ T cell‐mediated pathogenesis during liver cirrhosis. Methods: The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity‐related indicators of CD38+HLA‐DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA‐DR+CD8+ T‐cell killing was detected using cytotoxicity and antibody‐blocking assays. Results: The proportion of CD38+HLA‐DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate‐like functional characteristics. This CD8+ T‐cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity‐related cytokines, granzyme B and perforin. IL‐15 promoted CD38+HLA‐DR+CD8+ T‐cell activation and proliferation, inducing significant TCR‐independent cytotoxicity mediated through NKG2D. Conclusions: CD38+HLA‐DR+CD8+ T cells correlated with cirrhosis‐related liver injury and contributed to liver damage by signalling through NKG2D in a TCR‐independent manner. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a common cause of acute hepatitis, with increasing incidence in Europe, including Romania. Concurrently, Romania has a high prevalence of chronic hepatitis B (CHB). There is limited research on the clinical presentation and outcomes of HEV infection in patients with pre-existing chronic hepatitis B (CHB), especially in resource-rich settings. Most literature data come from South, East, and Southeast Asia. A review of the literature on HEV and HBV co-infection indicates a severe prognosis, particularly in patients with underlying liver disease. However, the cases in this study, which did not display cirrhosis, showed varied outcomes. The role of anti-HBV treatment in improving prognosis remains uncertain and warrants further investigation. Acute HEV infection superimposed on chronic HBV infection poses significant clinical challenges, with outcomes ranging from full recovery to fatality. Preventive measures, including sanitation and vaccination against HBV, are crucial. More studies are needed to establish effective treatment protocols for this co-infection. In this study, we will analyze the clinical setting, diagnosis, particularities, and outcomes of five such cases of dual hepatotropic viral infection recorded over a period of 6 years (2018–2023) at a large Infectious Diseases clinic in Bucharest, Romania. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection remains a significant global health challenge, leading to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) and integrated HBV DNA are pivotal in maintaining viral persistence. Recent advances in CRISPR/Cas technology offer innovative strategies to inhibit HBV by directly targeting both cccDNA and integrated HBV DNA or indirectly by degrading HBV RNAs or targeting host proteins. This review provides a comprehensive overview of the latest advancements in using CRISPR/Cas to inhibit HBV, with a special highlight on newer non-double-strand (non-DSB) break approaches. Beyond the canonical use of CRISPR/Cas for target inhibition, we discuss additional applications, including HBV diagnosis and developing models to understand cccDNA biology, highlighting the diverse use of this technology in the HBV field. [ABSTRACT FROM AUTHOR]

Hepatitis B and Hepatitis C are viral causes of Hepatitis that lead to significant worldwide mortality and morbidity through the sequelae of fibrosis and hepatocellular carcinoma. In this review, we have summarized recent studies that have examined the effects of antiviral therapy on the regression of fibrosis and the reduction in mortalities associated with the viruses. Antiviral therapy significantly decreases mortality and induces the regression of fibrosis. [ABSTRACT FROM AUTHOR]

Human Na+-taurocholate cotransporting polypeptide (hNTCP) is predominantly expressed in hepatocytes, maintaining bile salt homeostasis and serving as a receptor for hepatitis B virus (HBV). hNTCP expression is downregulated during hepatocellular carcinoma (HCC) development. In this study, we investigated the molecular mechanisms underlying hNTCP dysregulation using HCC tissues and cell lines, and primary human hepatocytes (PHHs). Firstly, we observed a significant reduction of hNTCP in HCC tumors compared to adjacent and normal tissues. Additionally, hNTCP mRNA levels were markedly lower in HepG2 cells compared to PHHs, which was corroborated at the protein level by immunoblotting. Sanger sequencing confirm ed identical sequences for hNTCP promoter, exons, and mRNA coding sequences between PHH and HepG2 cells, indicating no mutations or splicing alterations. We then assessed the epigenetic status of hNTCP. The hNTCP promoter, with low CG content, showed no significant methylation differences between PHH and HepG2 cells. Chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR) revealed a loss of activating histone posttranslational modification (PTM) H3K27ac near the hNTCP transcription start site (TSS) in HepG2 cells. This loss was also confirmed in HCC tumor cells compared to adjacent and background cells. Treating HepG2 cells with histone deacetylase inhibitors enhanced H3K27ac accumulation and glucocorticoid receptor (GR) binding at the hNTCP TSS, significantly increasing hNTCP mRNA and protein levels, and rendering the cells susceptible to HBV infection. In summary, histone PTM-related epigenetic mechanisms play a critical role in hNTCP dysregulation in liver cancer cells, providing insights into hepatocarcinogenesis and its impact on chronic HBV infection. [ABSTRACT FROM AUTHOR]

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research's importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process. [ABSTRACT FROM AUTHOR]

Aim: Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug‐resistance mutation. However, in patients lacking drug‐resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug‐resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF. Methods: This prospective study included 25 patients with serum HBV‐DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing. Results: LAM‐PR, LAM‐BTH, ETV‐PR, and ETV‐BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM‐BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV‐PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV‐DNA remained undetectable up to 48 weeks in all patients. Conclusion: Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera. [ABSTRACT FROM AUTHOR]

Beclin 1 protein encoded by the BECN1 gene plays a critical role in the autophagy pathway which is utilized by the Hepatitis B virus (HBV) for its replication. HBV is known for the subversion of the host's autophagy process for its multiplication. The aim of this study was to determine the role of BECN1 intronic variants in HBV susceptibility. Intronic region variant rs9890617 was analyzed using Human splicing finder v3.1 and was found to alter splicing signals. A total of 712 individuals (494 HBV infected and 218 healthy controls) were recruited in the study and genotyped by applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP). Statistical analysis revealed that the mutant allele T of rs9890617 was significantly associated with the overall disease risk in the allelic model (OR 1.41; 95%CI 1.00–1.99, p = 0.04). On stratifying the data based on the different stages of HBV infection, the mutant genotype showed a significant association with the chronic group in allelic (OR 1.62; 95%CI 1.11–2.39, p = 0.01), dominant (OR 1.64; 95%CI 1.07–2.52, p = 0.02), and co-dominant (OR 1.55; 95%CI 1.00–2.40, p = 0.04) models. Overall, this is the first study regarding beclin 1 variant rs9890617 and we found a significant association of the mutant T allele with the genetic predisposition to HBV infection. [ABSTRACT FROM AUTHOR]

Transcription termination fine-tunes gene expression and contributes to the specification of RNA function in eukaryotic cells. Transcription termination of HBV is subject to the recognition of the canonical polyadenylation signal (cPAS) common to all viral transcripts. However, the regulation of this cPAS and its impact on viral gene expression and replication is currently unknown. To unravel the regulation of HBV transcript termination, we implemented a 3' RACE (rapid amplification of cDNA ends)-PCR assay coupled to single molecule sequencing both in in vitro -infected hepatocytes and in chronically infected patients. The detection of a previously unidentified transcriptional readthrough indicated that the cPAS was not systematically recognized during HBV replication in vitro and in vivo. Gene expression downregulation experiments demonstrated a role for the RNA helicases DDX5 and DDX17 in promoting viral transcriptional readthrough, which was, in turn, associated with HBV RNA destabilization and decreased HBx protein expression. RNA and chromatin immunoprecipitation, together with mutation of the cPAS sequence, suggested a direct role of DDX5 and DDX17 in functionally linking cPAS recognition to transcriptional readthrough, HBV RNA stability and replication. Our findings identify DDX5 and DDX17 as crucial determinants of HBV transcriptional fidelity and as host restriction factors for HBV replication. HBV covalently closed circular (ccc)DNA degradation or functional inactivation remains the holy grail for the achievement of HBV cure. Transcriptional fidelity is a cornerstone in the regulation of gene expression. Here, we demonstrate that two helicases, DDX5 and DDX17, inhibit recognition of the HBV polyadenylation signal and thereby transcriptional termination, thus decreasing HBV RNA stability and acting as restriction factors for efficient cccDNA transcription and viral replication. The observation that DDX5 and DDX17 are downregulated in patients chronically infected with HBV suggests a role for these helicases in HBV persistence in vivo. These results open new perspectives for researchers aiming at identifying new targets to neutralise cccDNA transcription. [Display omitted] • We uncovered a heterogeneous transcriptional termination of HBV transcripts in cellular models and in patients with CHB. • HBV transcription termination is functionally linked to HBV replication. • RNA helicases DDX5 and DDX17 promote HBV transcriptional read-through and viral RNA destabilisation. • DDX5 and DDX17 are host HBV restriction factors and are downregulated in patients with CHB. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) cells are amongst the most important innate immune cells against hepatitis B virus (HBV) infection. Moreover, previous studies have shown that HBV infection induced TREM-1+ expression in monocyte and secretion of inflammatory cytokines. Thus, this prompted us to elucidate the role of TREM-1+ monocytes in regulating the function of iNKT cells. Ninety patients and 20 healthy participants were enrolled in the study. The percentage and phenotype of iNKT cells and TREM-1+ monocytes were measured in the peripheral blood of healthy controls (HC), patients with chronic HBV infection (CHB), HBV-related liver cirrhosis (LC), and HBV-related acute-on-chronic liver failure (ACLF) via flow cytometry. Moreover, co-culture experiments with iNKT cells and TREM-1 overexpressing THP-1 cells were performed to determine the role of TREM-1 in the regulation of NKT cell function. We observed that the percentage of iNKT cells and CD4−iNKT cells gradually decreased, whereas the percentage of CCR2+TREM-1+ monocytes increased with the progression of the disease. In addition, activation of the TREM-1 signaling pathway induced the secretion of inflammatory cytokines leading to pyroptosis of iNKT cells and secretion of IL-17 contributing towards disease progression. Therefore, this study suggests that blocking the activation of TREM-1 in monocytes could promote the elimination of HBV by inhibiting pyroptosis of iNKT cells and restoring their function. However, further studies are required to validate these results that would help in developing new treatment strategies for patients with HBV infections. [ABSTRACT FROM AUTHOR]

This paper explores the application of conceptual hydrological models in optimizing the operation of hydroelectric power plants (HPPs) in steppe regions, a crucial aspect of promoting low-carbon energy solutions. The study aims to identify the most suitable conceptual hydrological model for predicting reservoir inflows from multiple catchments in a steppe region, where spring runoff dominates the annual water volume and requires careful consideration of snowfall. Two well-known conceptual models, HBV and GR6J-CemaNeige, which incorporate snow-melting processes, were evaluated. The research also investigated the best approach to preprocessing historical data to enhance model accuracy. Furthermore, the study emphasizes the importance of accurately defining low-water periods to ensure reliable HPP operation through more accurate inflow forecasting. A hypothesis was proposed to explore the relationship between atmospheric circulation and the definition of low-water periods; however, the findings did not support this hypothesis. Overall, the results suggest that combining the conceptual models under consideration can lead to more accurate forecasts, underscoring the need for integrated approaches in managing HPP reservoirs and promoting sustainable energy production. [ABSTRACT FROM AUTHOR]

Hydropower is becoming an important renewable energy source in Turkey, but the ever-changing atmospheric and climatic conditions of Turkey make it very difficult to be projected efficiently. Thus, an efficient estimation technique is crucial for it to be adopted as a reliable energy source in the future. This study evaluates Turkey's hydropower potential in the Euphrates–Tigris Basin under changing climatic conditions. We adapted an empirical equation to model reservoir outflows, considering the site-specific characteristics of 14 major dams. Initial results from employing a model with a constant empirical coefficient, α, yielded moderate predictive accuracy, with R2 values ranging from 0.289 to 0.612. A polynomial regression identified optimal α values tailored to each dam's surface area, significantly improving model performance. The adjusted α reduced predictive bias and increased R2 values, enhancing forecast reliability. Seasonal analysis revealed distinct hydropower trends: Ataturk Dam showed a notable decrease of 5.5% in hydropower generation up to 2050, while Birecik and Keban Dams exhibited increases of 2.5% and 2.2%, respectively. By putting these discoveries into practice, water resource management may become more robust and sustainable, which is essential for meeting Turkey's rising energy needs and preparing for future climatic challenges. This study contributes valuable insights for optimizing reservoir operations, ensuring long-term hydropower sustainability, and enhancing the resilience of water resource management systems globally. [ABSTRACT FROM AUTHOR]

Viral hepatitis (A–E) presents a major global health challenge. In 2015, the World Health Organization (WHO) launched an initiative to eliminate viral hepatitis, with the aim of reducing new infections by 90% and deaths by 65% by 2030. Mexico is one of 38 focus countries identified by the WHO, collectively accounting for 80% of global infections and deaths. While hepatitis B and C are commonly diagnosed in Mexico, routine diagnosis for hepatitis D and E is lacking, with no specific epidemiological data available. In 2020, Mexico implemented the National Hepatitis C Elimination Program, focusing on preventing new infections, reducing complications like cirrhosis and hepatocellular carcinoma, ensuring access to treatment, and improving patient care. However, this program has not been extended to hepatitis B and E. Addressing the challenges of viral hepatitis control in Mexico requires increased resource allocation, expanded diagnosis, vaccination for hepatitis A and B, and treatment coverage for hepatitis B and C, along with multisectoral engagement. This work provides an overview of Mexico's response to the global initiative, highlighting its progress, challenges, and areas of opportunity. [ABSTRACT FROM AUTHOR]

Next generation sequencing (NGS) provides an accurate analysis of hepatitis B virus (HBV) as compared to Sanger sequencing. In 2019, samples from HBV infected family of mother and her two sons samples were collected from Lahore, Pakistan. Sequencing of S gene, Geno2pheno (HBV) 2.0 tool and GHOST platform were used to analyze the genotype, mutations (natural and escape) and quasispecies analysis of the HBV. All samples in family were infected with genotype HBV/D1 and had high viral load (10e8 IU). An vaccine escape mutation "C137W" was identified in mother and a son. Mother sample were shown more number of haplotypes and total diversity as compared to sons. The quasispecies analysis showed the mother and sons were infected with HBV having similar genetic makeup, indicating the vertical transfer of infection. This case study provides knowledge about genetic variations that contributes to the improved diagnosis of the infection, treatment therapy, follow-up, and future treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: To identify HBV-related genes (HRGs) implicated in osteoporosis (OP) pathogenesis and develop a diagnostic model for early OP detection in chronic HBV infection (CBI) patients. Methods: Five public sequencing datasets were collected from the GEO database. Gene differential expression and LASSO analyses identified genes linked to OP and CBI. Machine learning algorithms (random forests, support vector machines, and gradient boosting machines) further filtered these genes. The best diagnostic model was chosen based on accuracy and Kappa values. A nomogram model based on HRGs was constructed and assessed for reliability. OP patients were divided into two chronic HBV-related clusters using nonnegative matrix factorization. Differential gene expression analysis, Gene Ontology, and KEGG enrichment analyses explored the roles of these genes in OP progression, using ssGSEA and GSVA. Differences in immune cell infiltration between clusters and the correlation between HRGs and immune cells were examined using ssGSEA and the Pearson method. Results: Differential gene expression analysis of CBI and combined OP dataset identified 822 and 776 differentially expressed genes, respectively, with 43 genes intersecting. Following LASSO analysis and various machine learning recursive feature elimination algorithms, 16 HRGs were identified. The support vector machine emerged as the best predictive model based on accuracy and Kappa values, with AUC values of 0.92, 0.83, 0.74, and 0.7 for the training set, validation set, GSE7429, and GSE7158, respectively. The nomogram model exhibited AUC values of 0.91, 0.79, and 0.68 in the training set, GSE7429, and GSE7158, respectively. Non-negative matrix factorization divided OP patients into two clusters, revealing statistically significant differences in 11 types of immune cell infiltration between clusters. Finally, intersecting the HRGs obtained from LASSO analysis with the HRGs identified three genes. Conclusion: This study successfully identified HRGs and developed an efficient diagnostic model based on HRGs, demonstrating high accuracy and strong predictive performance across multiple datasets. This research not only offers new insights into the complex relationship between OP and CBI but also establishes a foundation for the development of early diagnostic and personalized treatment strategies for chronic HBV-related OP. [ABSTRACT FROM AUTHOR]

AbstractTo elucidate the structure-activity relationship of 17 matrine alkaloids from Oxytropis ochrocephala Bunge, their effect on hepatitis B surface antigen (HBsAg) secretion was studied using the MTT assay. A 3D-QSAR analysis showed a strong correlation between chemical structures and biological activities (q2 = 0.625, r2 = 0.859). Molecular docking and molecular dynamics simulations revealed that hydrogen bonding and hydrophobic interactions with hepatitis B core protein (PDB:5T2P) are key to inhibiting HBsAg secretion, suggesting potential for developing natural anti-hepatitis B drugs. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the objective of this work was to investigate the potential relationship between the elevated expression of RRM2 in HBV-related HCC and the influence of HBx on this expression. The study attempted to determine the specific mechanism by which RRM2 is implicated in the promotion of hepatocarcinogenesis by HBx. There have been multiple scholarly proposals suggesting that the induction of autophagy by HBx is a significant intermediary factor in the development of HCC. However, the precise carcinogenic function of HBx-induced autophagy remains a subject of debate. Results: This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis. Conclusions: Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC. [ABSTRACT FROM AUTHOR]

Background: The safety of blood donation requires screening for transfusion-transmitted infections, including human immunodeficiency virus (HIV), syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). This study aimed to determine the seroprevalence of HIV, HBV, HCV and syphilis in blood donors of Mogadishu Tertiary Care Hospital, Somalia from 2020 to 2022. Methods: The records of 109,385 blood donors who attended our blood center in Mogadishu-Somalia between 2020 and 2022 were examined retrospectively. Serum samples of donors; HBsAg, anti-HCV, anti-HIV and syphilisscreening tests were studied using the microparticleEnzyme-Linked ImmunoSorbent Assay (ELISA)(Vitros, Ortho-Clinical Diagnostics, U.S) method.The distribution of HBsAg, anti-HCV, anti-HIV and syphilis positivity rates of 109,385 blood donors according to years, gender and age were examined. Kolmogorov Smirnov, Skewness, Kurtosis tests and histogram were used for normality analysis. Chi-squared test (χ2) and Fisher Exact test were used to analyze categorical data. Categorical variables were expressed as frequency (percentage). Analysis of continuous data was performed with the Mann Whitney U test. P < 0.05 value was considered statistically significant. Results: HBsAg positivity was found in 0.6% of the donors, anti-HCV positivity in 0.01%, anti-HIV positivity in 0.03% and syphilispositivity in 0.3%. The results showed that among the blood donors, the prevalence of syphilis, HIV, Hepatitis B, and Hepatitis Cwas notably low. Conclusion: The prevalence of HBV, HCV, HIV, and syphilis among blood donors in Somalia was found to be quite low. Even if our found seroprevalence rates are low, to guarantee the safety of blood for recipients, strict selection of blood donors and thorough screening of donors' blood using accepted procedures are strongly advised. [ABSTRACT FROM AUTHOR]

Blood transfusion has a hazard of transmission of many pathogens, including Toxoplasma gondii (T. gondii) and other venereal infections. It is crucial to conduct epidemiological surveillance to detect the prevalence of these pathogens. The study aimed to assess the seroprevalence of T. gondii and common transfusable venereal infections among healthy blood donors in Menoufia Province, Egypt, and identify associated risk factors. Four hundred twenty individuals were recruited between January and April 2023 for cross-sectional descriptive research from the blood banks of Menoufia University medical hospitals. Collected blood samples were screened for anti-T. gondii IgM and IgG, HBsAg, anti-HCV antibodies, HIV p24 antigen and anti-HIV antibodies, and anti-Treponema pallidum antibodies. 46 (11.0%) and 22 donors (5.2%) individuals tested positive for anti-T. gondii IgG with a 95% CI (8.3–14.6) and IgM with a 95% CI (3.5–8.1), respectively, while one patient (0.2%) was positive for both antibodies. Regarding venereal infections, 12 (2.9%) were positive for HBV, 6 (1.4%) were positive for HCV, 7 (1.7%) were positive for HIV, and none of the tested population showed positivity for syphilis. Female gender, consumption of raw meat, agricultural environment, poor awareness about T. gondii, and blood group type (especially AB and O groups) were identified as independent risk factors for T. gondii infection. The study highlights the importance of testing blood donors for T. gondii and common transfusable venereal illnesses. Starting health education programs and preventative measures, such as suitable meat handling and cleanliness practices, is critical for minimizing the occurrence of these illnesses. Larger-scale additional study is advised to confirm these results and provide guidance for public health initiatives. [ABSTRACT FROM AUTHOR]

Background and Objectives In addition to supplying safe and sufficient blood and blood components, Iranian Blood Transfusion Organization (IBTO) has supplied surplus plasma for plasma fractionation to produce plasma-derived medicine products (PDMPs) since 2005. The look-back process is a requirement for contract fractionation and aims to improve the safety of PDMPs and blood components. This study investigates the trend of look-back units due to repeatedly reactive screening test results during 2018-2021. Materials and Methods In this serial cross-sectional study, the data gathered from the look-back form, including the number of lookback cases, lookback due to repeatedly reactive samples, confirmatory test results, and changes in test kits. The data were entered into SPSS software, and statistical analysis were carried out using the chi-square test and incidence rate ratio in R software. Results In 2019, after changing the screening methods and kits, there was a significant increase in the look-back rate and the number of repeatedly reactive samples in screening tests. The prevalence of repeatedly reactive samples in the HBsAg screening test was lower than that of HIV and HCV. The confirmatory test showed negative results for HCV and HIV at rates of 85% and 90%, respectively. Conclusions The change in screening methods and kits can lead to an increase in repeatedly reactive samples, resulting in a higher rate of look-back units and plasma waste. [ABSTRACT FROM AUTHOR]

As healthcare workers run a high and constant occupational risk of hepatitis B virus (HBV) infection through exposure to biological material, vaccination is mandatory as well as the monitoring of antibody levels one to two months after complete immunisation. The aim of this descriptive cross-sectional study was to determine HBV vaccine coverage of 200 primary and secondary healthcare workers (100 each) from Šabac, Serbia and their blood anti-HBs titre. We also wanted to identify factors that could predict the titre. Anti-HBV vaccination covered all participants, of whom 89.5 % were fully vaccinated, and 85 % had a protective antibody titre. We found a statistically significant association between antibody titre and the number of received vaccine doses, chronic jaundice, autoimmune disease, and cancer in our participants. The fact that 15 % did not achieve the protective antibody titre confirms the necessity of its control after immunisation, which is not routinely carried out in most countries, Serbia included. It is, therefore, necessary to develop a detailed strategy for monitoring vaccination and serological status of healthcare workers in order to improve their safety at work. An important role should also be given to continuous education of healthcare workers from the beginning of schooling to the end of their professional career. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of hepatitis B virus (HBV) inhibiting M1 macrophages to promote immune escape, and to provide targets and strategies for antiviral therapy. Methods: The human monocyte cell line THP-1 was induced into M1 macrophages with PMA+LPS+IFN-γ. Cell morphological changes and the expressions of CD68, CD86, HLA-DR and functional molecules IL-1β, IL-6, TNF-α in M1 macrophages were detected by flow cytometry and RT-qPCR to identify M1 macrophages. HBV stable replication cell line HepG2.2.15 were co-cultured with M1 macrophages, and the expression of HBV-DNA was detected by qPCR. The expression of CD68, CD86 and HLA-DR were detected by flow cytometry. The expressions of functional molecules TLR4, NLRP3, Caspase-1, pro-caspase-1, caspase-1 p20, IL-1β and IL-18 in M1 macrophages were determined by RT-qPCR and Western blot. Apoptosis rate was detected by flow cytometry, and the expression of apoptosis related protein cleaved-caspase-3 was determined by Western blot. Results: THP-1 was successfully induced to differentiate into M1 macrophages. M1 macrophages inhibited HBV replication (P<0.05). HBV inhibited the expressions of CD68, CD86 and HLA-DR in M1 macrophages（P<0.01). HBV inhibited the expressions of TLR4, NLRP3, Caspase-1, caspase-1 p20, IL-1β and IL-18 in M1 macrophages (P<0.01). HBV induced M1 macrophage apoptosis (P<0.05). Conclusion: HBV inhibits M1 macrophages and their functional molecules TLR4, NLRP3 and downstream factors, reduces the synthesis and secretion of inflammatory factors, induces apoptosis, and then promotes immune escape, resulting in the persistence and replication of HBV in the body. [ABSTRACT FROM AUTHOR]

Aim: To analyse hepatitis b and hepatitis c co-infections among patients at tertiary care centre. Methods: This study was a retrospective analysis of data of patients with chronic liver disease who were tested for both HBV and HCV between January 2022 and December 2022. A total of 2100 patients were included in the analysis. Demographic and clinical data were collected from medical records, including age, sex, and area status. Clinical data included rapid card test results. The primary outcome variable was the presence of co-infection with both HBV and HCV. Results: Out of 2100 patients, 522 (25%) patients had viral hepatitis infections. 15.2% of patients had HCV mono-infection, 9.2% had HBV mono-infection, and 0.3% had coinfection with both HBV and HCV. Overall 70.3% were male and 29.7% female prevalent to this infection and the most common age group was 21-40 age. The mean age among the study group was 47 years. Approximately 77.8% of cases were from rural regions. Conclusion: Co-infection with HBV and HCV is relatively uncommon among patients. However, it is still an important issue to consider, as it can lead to more severe liver disease and lower treatment response rates. [ABSTRACT FROM AUTHOR]

Functional cure for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation with the goal of achieving functional cure are the small-interfering RNA JNJ-73763989 (JNJ-3989) and the capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir). REEF-2, a phase IIb, double-blind, placebo-controlled, randomized study, enrolled 130 nucleos(t)ide analogue (NA)–suppressed hepatitis B e-antigen (HBeAg)–negative patients with CHB who received JNJ-3989 (200 mg subcutaneously every 4 weeks) + JNJ-6379 (250 mg oral daily) + NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 +active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up. At follow-up Week 24, no patients achieved the primary endpoint of functional cure (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved functional cure at follow-up Week 48. There was a pronounced on-treatment reduction in mean HBsAg from baseline at Week 48 in the active arm vs. no decline in the control arm (1.89 vs. 0.06 log 10 IU/ml; p = 0.001). At follow-up Week 48, reductions from baseline were >1 log 10 IU/ml in 81.5% vs. 12.5% of patients in the active and control arms, respectively, and 38/81 (46.9%) patients in the active arm achieved HBsAg <100 IU/ml vs. 6/40 (15.0%) patients in the control arm. Off-treatment HBV DNA relapse and alanine aminotransferase increases were less frequent in the active arm, with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NAs during follow-up. Finite 48-week treatment with JNJ-3989 + JNJ-6379 + NA resulted in fewer and less severe post-treatment HBV DNA increases and alanine aminotransferase flares, and a higher proportion of patients with off-treatment HBV DNA suppression, with or without HBsAg suppression, but did not result in functional cure. Achieving a functional cure from chronic hepatitis B (CHB) with finite treatments is a major unmet medical need. The current study assessed the rate of functional cure and clinical outcome after controlled nucleos(t)ide analogue (NA) withdrawal in patients with low levels of HBsAg induced by 48 weeks of treatment with the small-interfering RNA JNJ-3989 and the capsid assembly modulator JNJ-6379 plus NA vs. patients who only received NA treatment. Though functional cure was not achieved by any patient in either arm, the 48-week treatment regimen of JNJ-3989, JNJ-6379, and NA did result in more patients achieving pronounced reductions in HBsAg, with clinically meaningful reductions maintained for up to 48 weeks off all treatments, as well as fewer off-treatment HBV DNA increases and alanine aminotransferase flares. These findings provide valuable insights for future studies investigating potential finite treatment options, while the reported efficacy and safety outcomes may be of interest to healthcare providers making treatment decisions for patients with NA-suppressed HBeAg-negative CHB. NCT04129554. [Display omitted] • No functional cure achieved 24 or 48 weeks after 48 weeks of JNJ-3989 + JNJ-6379 + NA. • All patients had pronounced declines in HBsAg after 48 weeks of JNJ-3989 + JNJ-6379 + NA. • Maintained HBsAg declines from JNJ-3989 + JNJ-6379 + NA up to 48-weeks off-treatment. • Pronounced HBV DNA and HBsAg suppression off-treatment after JNJ-3989 + JNJ-6379 + NA. • JNJ-3989 + JNJ-6379 treatment was safe and well tolerated. [ABSTRACT FROM AUTHOR]

The preS1 region of the large hepatitis B virus (HBV) surface protein is a crucial component in HBV infection; however, its impact on the development of hepatocellular carcinoma (HCC) remains unknown. This study investigated the relationship between serum preS1 levels and hepatocarcinogenesis in patients with chronic hepatitis B (CHB). The preS1 levels were measured in 531 patients with CHB without a history of HCC. Among the patients, 293 HBV carriers who had never received nucleotide/nucleoside analog (NA) therapy had their preS1 levels measured at their first visit (non-NA group), and 238 patients who had received NA therapy had their preS1 levels measured at the start of NA administration (NA group). The two groups had no significant differences in hepatitis B surface antigen (HBsAg) levels; however, the NA group's preS1/HBsAg ratio was significantly higher. The preS1/HBsAg ratio was significantly different between patients with CHB not meeting the NA treatment criteria and patients with chronic hepatitis and cirrhosis who were eligible for NA treatment. The predictors of HCC development were analyzed, and the preS1/HBsAg ratio was identified in both groups. The preS1/HBsAg ratio could predict hepatocarcinogenesis in patients with CHB with or without NA administration. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and Hepatitis E virus (HEV) are zoonotic pathogens posing significant health concerns in rural Amazonia, a region marked by high endemicity, poverty, and limited healthcare access. However, the epidemiology of HBV and HEV in this ecosystem remains underexplored. This study examines the circulation of HBV and HEV at the human–wildlife interface and identifies risk factors within an isolated Amazonian indigenous community reliant on hunting for subsistence. Antibodies against HBV core antigens (HBcAbs) were found in three wildlife species: Cuniculus paca (0.8%), Tayassu pecari (1.6%), and Mazama americana (4.1%), marking the first record of HBV antibodies in free-ranging wildlife in the Amazon. However, further research is necessary to identify circulating strains and their relation to human HBV. HBcAbs were also detected in 9.1% of human samples, confirming exposure to HBV in the region. HEV IgG antibodies were present in 17.1% of humans and were associated with higher age. All wildlife and domestic animal samples tested negative for HEV, but transmission through consumption of wild animals and contaminated water needs further investigation. The identified risk factors highlight the urgent need for measures to promote safer food handling, improved sanitation, hygiene, and practices related to contact with wild animals. [ABSTRACT FROM AUTHOR]

Functional cure, defined as durable loss of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA suppression off therapy, is an increasingly important goal in the treatment of chronic hepatitis B. Although novel treatments aimed at achieving functional cure are being developed and tested in clinical trials, it is important to assess the perspectives of people living with HBV towards these potential treatments and their participation in HBV functional cure research. We have performed a scoping review that revealed that there is limited knowledge regarding patient perspectives of HBV functional cure research and then identified gaps in knowledge for further investigation. Our work highlights the need for further studies in patient perspectives in HBV functional cure research.

Introduction. Hepatotropic viruses (HAV, HBV, HCV, HDV, and HEV) significantly impact global health, with varying prevalence across regions. Objective. This study aims to systematically consolidate data from diverse meta-analyses to provide a contemporary reference on virus distribution and prevalence. Materials and methods. Adhering to PRISMA guidelines, the study utilized a mixed effects model for data integration. Quality evaluation was carried out with QUOROM and AMSTAR tools, with heterogeneity assessed via the Higgins I2 statistic, Q-statistic and Tau squared (τ2) values. Results. The study analyzed 86 meta-analyses from 56 studies (2017–2022) with minimal overlap. Prevalence rates by region were as follows: MENA – 29.2%, Afghanistan – 9.14%, Africa – 8.10%. Prevalence rates by virus type: HAV – 82.5%, HBV – 8.6%, HCV – 15.1%, HDV – 8.9%, HEV – 13.9%, dual HBV-HCV coinfection – 2.2%. Prevalence rates by risk groups: general population – 8.3%, healthcare workers – 4.0%. Continent-specific HBV-HCV prevalence rates: Africa – 9.2%, China – 6.9%, others. HCVprevalence rates among at-risk groups: healthcare workers – 5.58%, hemodialysis patients – 34.8%. Regional HCV rates: Africa – 7.42%, Middle East – 25.30%. Conclusion. Diverse global hepatotropic virus prevalence patterns are influenced by multifaceted factors. MENA faces higher rates due to healthcare challenges, while Africa struggles with limited resources. Tailored public health strategies, including vaccination and awareness campaigns, are essential to alleviate burdens and enhance global health. This consolidated data serves as a valuable resource for informed decision-making.

Abstract An effective vaccine against hepatitis C virus (HCV) should elicit both humoral and cellular immune responses. Previously, we characterized a bivalent vaccine candidate against hepatitis B (HBV) and HCV using chimeric HBV-HCV virus-like particles (VLP), in which the highly conserved epitope of HCV E2 glycoprotein (residues 412–425) was inserted into the hydrophilic loop of HBV small surface antigen (sHBsAg). While sHBsAg_412–425 elicited cross-neutralizing antibodies, it did not trigger a T-cell response against HCV. Thus, this study aimed to develop a vaccine candidate engaging both arms of adaptive immune response, potentially offering stronger protection against HCV. We evaluated the immunogenicity of minicircle (MC) DNA vaccines encoding sHBsAg_412–425 and HCV nonstructural (NS) proteins in BALB/c mice. Co-administration of sHBsAg_412–425 and NS induced a potent T-cell response, especially against NS3 and high titers of antibodies specific to HCV E2. Additionally, these antibodies recognized native HCV envelope glycoprotein heterodimers (E1E2) across multiple HCV genotypes and showed binding profiles to E1E2 alanine mutants comparable to the broadly neutralizing AP33 antibody. Overall, the findings demonstrate that MC DNA vaccine incorporating both sHBsAg_412–425 and HCV NS protein sequences induces robust, T-cell and AP33-like antibody responses, highlighting its potential as pan-genotypic prophylactic vaccine against HCV.

Abstract Background Globally, sexually transmitted infections (STIs) collectively cause 2.3 million deaths and 1.2 million cases of cancer annually. However, the epidemiology of STIs in the Middle East and North Africa (MENA) is not well assessed because of various social and cultural factors. Methods A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and covering 23 MENA countries, 19 STIs, and data from 20,435,971 participants. PubMed, Embase, regional and international databases, and country-level reports were searched up to May 2024. Results The analysis revealed significant regional variations in the prevalence of STIs within the MENA region. In North Africa, the most common STIs were bacterial vaginosis (31%), human papillomavirus (HPV, 23%), and Candida spp. (15%). In the Gulf Cooperation Council region and Yemen, Ureaplasma (25%), nongonococcal urethritis (NGU, 16%), and Mycoplasma spp. (12%) were the predominant infections. In the Levant region, the top STIs were HPV (20%), hepatitis B virus (HBV, 9%), and Candida spp. (9%). In Iran, Ureaplasma spp. (18%), HPV (17%), and cytomegalovirus (8%) were the most prevalent infections, whereas Ureaplasma spp. (20%), Candida spp. (18%), and HPV (16%) were most frequently detected in Türkiye. Gender-based disparities were observed, with a higher prevalence of Ureaplasma spp., Neisseria gonorrhoeae, and herpes in men and higher rates of Mycoplasma spp., HPV, HBV, and Candida spp. in women. Overall, high rates of nongonococcal urethritis (16.3%), Ureaplasma spp. (13.7%), HPV (12.7%), and Candida spp. (9.4%) were recorded in the MENA region. Conclusions Most MENA countries lack national STI screening programs, and the reported data are primarily from symptomatic individuals. Establishing robust surveillance systems, addressing stigma and barriers to healthcare access, and expanding STIs screening and vaccination programs are crucial for accurately capturing the true burden of STIs in MENA countries.