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After the declaration Global Health Sector Strategy on Viral Hepatitis by the World Health Organization in 2016, the Turkish Government defined a national strategy covering 2018-2023 to reach goals by 2030. Following a participatory decision process and a series of workshops, the strategy was built on eight separate subheadings. Apart from the official Prevention and Control Program, two separate road maps for hepatitis B and C were developed to obtain targets accessible with the cooperation of the Viral Hepatitis Society and the Turkish Association for the Study of the Liver in 2018 and 2020, respectively. Up to 2023, achievements and the current situation of the National Viral Hepatitis Prevention and Control Program and the hepatitis B virus and hepatitis C virus road maps were assessed in detail on June 28th, 2022, by the subject matter experts in Turkey. Besides the officially reported achievement rate (42\%) of the Program in 2021, participants mentioned undesirable effects of the coronavirus disease-2019 pandemic, unregulated migration, low levels of professional and public awareness, and barriers to access to anti-viral treatment. Recommendations focused on increasing the efficiency of screening and surveillance by integrating the viral carrier identity of individuals into the national health information system, simplifying the drug supplement and treatment initiation process and insisting on education to raise awareness.

International audience; Background: Besides the prototypical hepatitis B virus (HBV) infectious particle, which contains a full-length double-stranded DNA (flDNA), additional circulating virus-like particles, which carry pregenomic RNA (pgRNA), spliced1RNA (sp1RNA) or spliced-derived DNA (defDNA) forms have been described. We aimed to determine the level of these four circulating forms in patients and to evaluate their impact on viral lifecycle.Methods: Chronic HBV untreated patients (n = 162), included in the HEPATHER cohort, were investigated. Pangenomic qPCRs were set up to quantify the four circulating forms of HBV nucleic acids (HBVnaf). In vitro infection assays were performed to address the impact of HBVnaf.Results: Hierarchical clustering individualized two clusters of HBVnaf diversity among patients: (1) cluster 1 (C1) showing a predominance of flDNA; (2) cluster 2 (C2) showing various proportions of the different forms. HBeAg-positive chronic hepatitis phase and higher viral load (7.0 ± 6.4 vs 6.6 ± 6.2 Log10 copies/ml; p < 0.001) characterized C2 compared to C1 patients. Among the different HBVnaf, pgRNA was more prevalent in C1 patients with high vs low HBV viral load (22.1% ± 2.5% vs 4.1% ± 1.8% of HBVnaf, p < 0.0001) but remained highly prevalent in C2 patients, whatever the level of replication. C2 patients samples used in infection assays showed that: (1) HBVnaf secretion was independent of the viral strain; (2) the viral cycle efficiency differed according to the proportion of HBVnaf in the inoculum, independently of cccDNA formation. Inoculum enrichment before infection suggests that pgRNA-containing particles drive this impact on viral replication.Conclusion: Besides the critical role of HBV replication in circulating HBVnaf diversity, our data highlight an impact of this diversity on the dynamics of viral cycle.Clinical trial registration: Patients were included from a prospective multicenter French national cohort (ANRS CO22 HEPATHER, NCT01953458).

Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), which required developing novel therapies targeting the inhibition of HBV transcription and replication due to current limited treatment options. We explored novel target for the development of novel therapies targeting the inhibition of HBV replication and transcription. The expression of Id1 and E2F4 in HCC cells and tissues was detected by qRT-PCR and western blot. We investigated the Id1 and E2F4-mediated transcription of HBV infection by using HepG2.2.15, HepAD38, HepG2-NTCP cell lines and AAV/HBV-infected mice. Interactions between the two host proteins and viral covalently closed circular DNA (cccDNA) were assessed using subcellular localization, protein-protein interaction, chromatin immunoprecipitation, and luciferase assays. Ectopic Id1 significantly reduced HBV transcription and replication in both HBV-expressing cells and AAV/HBV-infected mice. Id1 and E2F4 could form a heterodimer to prevent E2F4 from promoting HBV transcription and replication. E2F4 could directly bind to cccDNA and activate the HBV core promoter in cell lines. Furthermore, in vitro binding experiments confirmed that the sequence 1758'-TTAAAGGTC-1766', which is highly conserved among HBV genotypes, is the target site of the E2F4 homodimer. The findings suggest that E2F4 function as novel cccDNA-binding protein to directly activate HBV transcription by binding to Cp promoter region. Our results highlight the ability that E2F4 represent a pan-potential therapeutic target against HBV transcription and provide more clues to better understand the life cycle of HBV.

Acute hepatitis B virus (HBV) infection occasionally progresses to acute liver failure, often with poor prognosis. The appropriate pharmacological approach is yet to be established. Although nucleotide analogs (NA) and corticosteroids are candidates for the treatment of acute HBV infection, their therapeutic effects, especially their effect on HBV clearance, remain unclear. To clarify effects on the HBV clearance of combination therapy of NA and steroid pulse therapy (SPT) for acute HBV infection, we first analyze the effectiveness of this therapy in patients with HBV infection compared with NA monotherapy (NAM). Of the 57 consecutive patients with acute hepatitis B infection from May 2007 to December 2018, we have included 25 patients for this study, whom we followed up until HBV clearance. According to the administration of NA and SPT, we divided patients into two groups (NAM group and NA + SPT group) and compared their results. Of the 25 patients, 10 received NAM, whereas 15 received NA + SPT. There were no appreciable adverse effects related to SPT. The time required for the clearance of HBsAg (76 (43–116) days vs. 26 (14–51) days, p = 0.0418) and HBV-DNA (NAM group vs. NA + SPT group: 180 (83.5–220) vs. 69 (43–136) days, p = 0.0420) was significantly shorter in the NA + SPT group than in the NAM group. The hazard ratio of NA + SPT for the clearance of HBsAg and HBV-DNA were 0.45 (0.19–1.09) and 0.35 (0.14–0.89), respectively. In conclusion, we showed that NA + SPT promoted HBV elimination. These findings support the use of the NA + SPT combination for acute HBV infection without the concern of persistent HBV infection.

This study was carried out in the dental school of Ahram Canadian University in Egypt to investigate the knowledge and compliance of senior students and interns toward infection control practices. A self‑administered questionnaire was employed with questions pertinent to the participants’ knowledge of risks in the dental settings, the practice of hand hygiene, the use of protective equipment, and the management of sharp injuries, among others. Although the knowledge and practice of the 240 surveyed participants were good; they were not up to the coveted standards. Despite being an integral part of their curriculum, an alarming percentage (19.6%) of the participants denied receiving knowledge about infection control instructions. Meanwhile, only 72.5% were aware of being at risk in the dental settings, and 78.3% confirmed their practice of hand hygiene. On the other hand, 84.6% of the surveyed participants confirmed the availability of protective equipment and 94.2% of them expressed their willingness to apply infection control measures in the future. The defects in the knowledge and practice mandate corrective actions to promote and upgrade the students’ compliance. Meanwhile, other gaps can be rectified via developing state-of-the-art communicative strategies. Efforts are warranted to enhance the attitude and motivate the students to conform to the protective safety measures. With all the infection control procedures already established in dental schools, the challenge lies in improving the students’ compliance with these recommendations.

The aim of this study was to assess the prevalence of serological and molecular biological markers of viral hepatitis B and C among apparently healthy residents of the Southern Vietnam. The study material was represented by 397 blood serum samples collected from apparently healthy residents of the Southern Vietnam. The ELISA examination for presence of HBV and HCV markers involved HBsAg, anti-HBs IgG, anti-HBcore IgG, and anti-HCV qualitative determination. For HBV DNA and HCV RNA detection, nucleic acids were extracted from serum blood, and a test for virus detection was carried out by real-time PCR with hybridization fluorescence detection. Amplification and subsequent sequencing of HBV and HCV were performed using nested PCR with paired overlapping primers jointly flanking the target regions. Analysis of the overall prevalence of serological markers showed that among the apparently healthy individuals anti-HBsAg and anti-HCV antibodies were detected in 12.3% (95% CI: 9.27–15.99%) and 3.27% (95% CI: 1.76–5.53%) of individuals, respectively. The prevalence of HBsAg in men (19.1%) significantly exceeded that of found in women (5.9%), χ2 = 14.688 with p = 0.0001, df = 1, calculated odds ratio OR = 3.751 (95% CI: 1.892–7.439). Among apparently healthy patients, taking into account HBsAg-positive and negative samples, HBV DNA was detected in 26.95% (95% CI: 22.65–31.6%). HBV phylogenetic analysis showed that subtype B4 prevalence comprised 64.49%. Subtypes C1 (14.95%), B2 (9.35%), C2 (6.54%), C3 (0.93%), and C5 (3.74%) were also identified. HCV RNA was detected in 7 samples, which accounted for 1.76% (95% CI: 0.71–3.6%). Phylogenetic analysis showed that all HCV isolates belong to genotype 6, subtype 6a (100%).

Chronic hepatitis B virus (HBV) infection has become one of the leading causes of liver cirrhosis and hepatocellular carcinoma globally. The discovery of sodium taurocholate co-transporting polypeptide (NTCP), a solute carrier, as a key receptor for HBV and hepatitis D virus (HDV) has opened new avenues for HBV treatment. Additionally, it has led researchers to generate hepatoma cell lines (including HepG2-NTCP and Huh-7-NTCP) susceptible to HBV infection in vitro, hence, paving the way to develop and efficiently screen new and novel anti-HBV drugs. This review summarizes the history, function and critical findings regarding NTCP as a viral receptor for HBV/HDV, and it also discusses recently developed drugs targeting NTCP.

Meseret Ayelign,1 Melak Aynalem,2 Nega Berhane3 1Department of Molecular Biology, Specialized Referral Hospital, University of Gondar, Gondar, Ethiopia; 2Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 3Department of Biotechnology, College of Natural Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Melak AynalemDepartment of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Science, University of Gondar, P.O. Box 196, Gondar, EthiopiaTel +251 912692619Email melak.aynalem1234@gmail.comBackground: Viral infections are the most common diseases. Of them, human immunodeficiency virus (HIV), hepatitis B viruses (HBV), and hepatitis C viruses (HCV) are common. When HBV or HCV becomes co-morbid with HIV, they lead to severe forms of a disease and rapid death.Objective: This study aimed to determine the seroprevalence and associated factors of HBV and HCV among HIV-positive study participants.Methods: A cross-sectional study was conducted among 81 individuals, and a non-randomized purposive sampling technique was used. From each study participant, sociodemographic and clinical data were gathered by using a pretested questionnaire and data collection sheet, respectively. Further, a venous blood sample was collected for viral load count, and HBV and HCV determination. To keep the quality of test results, commercially prepared quality control samples were used. The data were entered to EPI-Info version 7 and analyzed by using SPSS version 20. The descriptive data were summarized in percentages, median, and IQR. Logistic regression was analyzed to determine associated factors. To say the data were statistically significant, the p-values should be less than 0.05.Results: A total of 81 study participants were included. Of them, 56.8% (46/81) and 67.9% (55/81) were female and urban residents, respectively. The prevalence of hepatitis co-infection was 21% (95% CI: 17%, 23%). Further, the prevalence of HBV/HIV and HCV/HIV was 13.5% (95% CI: 10.5%, 16.5%) and 8.6% (95% CI: 5.6%, 11.6%), respectively. Wise use of highly active antiretroviral therapy (HAART) 0.01 (0.00, 0.213) was a preventive factor to hepatitis infection.Conclusion and Recommendation: The HBV and HCV co-infection among HIV-positive patients was a significant public health concern. Also, having wise use of HAART can reduce exposure to hepatitis co-infection. Therefore, clear strategies on hepatitis screening and wise use of HAART to HIV would be critical.Keywords: seroprevalence, HBV, HCV, HIV, Gondar, Ethiopia

Introduction: in the review, we aimed to present current knowledge about the risk of infection, standards of care, and postexposure prophylaxis (PEP) in pediatric patients after non-vertical exposures to HIV, HBV, and HCV infection. Materials and Methods: the latest available literature and recommendations of Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), European recommendations for the management of HIV and administration of non-occupational PEP, and Polish AIDS Society were reviewed. Results: the majority of cases of non-vertical exposure to blood-borne viruses in the pediatric population consist of sexual exposition and injection with unsterilized sharp objects (usually needlestick injuries). The risk HIV, HBV, and HCV transmission depend on several factors, and each exposure should be evaluated individually with consideration of the patient’s medical history. It is crucial to start antiretroviral therapy within 48 h from exposure. Treatment is continued for 28 days, and a 3-drugs regiment is recommended in the majority of cases. Decisions on hepatitis B and tetanus PEP are based on a history of vaccination. There is no PEP for hepatitis C infection, follow-up testing aims for early identification of disease and consideration of treatment options. Conclusion: all children after the non-vertical exposure to HIV, HBV, and HCV infection should be evaluated by the Infectious Disease specialist as soon as possible after the incident and qualified to post-exposure prophylaxis. Systematic diagnostic and follow-up on children after significant needlestick exposure should be maintained. Children after sexual exposure need a multidisciplinary approach. Response to reported event must be rapid and treatment must be comprehensive.

Jushan Sun,1 Yibiao He,1 Lei Bai,1 Zhipeng Wang,1 Zhu Cao,1 Yingmei Shao,2 Jinming Zhao1 1Department of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of China; 2Xinjiang Uyghur Autonomous Region Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People’s Republic of ChinaCorrespondence: Jinming ZhaoDepartment of Liver and Laparoscopic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137 of Liyushan Street, Xinshi District, Urumqi, Xinjiang, 830054, People’s Republic of ChinaTel/Fax +86-991-4364529Email zhaojm_m@outlook.comObjective: To investigate the risk factors related to new-onset diabetes mellitus (NODM) and the significance of IL-6.Methods: A retrospective analysis was conducted on clinical data from 64 patients who received either a living donor liver transplantation or a donation after circulatory death from September 2013 to October 2020 and attended regular follow-up visits for six or more months. During follow-up, patients were randomized into groups and followed up until the completion of the study or the death of the patient.Results: The incidence of NODM was 31.25% (n = 20). The median age in the NODM group was 52.15 years (p < 0.01). Age (OR = 1.089; 95% CI: 0.0211– 0.1495, p = 0.003) and elevated preoperative IL-6 (OR = 1.122; 95% CI: 0.0619– 0.1677, p = 0.029) were found to be independent risk factors for NODM. HBV-induced liver cirrhosis, warm ischemia time (WIT), body mass index (BMI), and high preoperative fasting blood glucose (FBG) were also found to be risk factors for NODM. The recipient had a higher risk of NODM if the donor had a high BMI and poor hepatic function. The concentrations of IL-6, procalcitonin (PCT), FBG, and tacrolimus (TAC) in the first month postoperatively were significantly higher in the NODM group than in the NO-NODM group. The survival rate of the patients was not affected by NODM.Conclusion: HBV-induced liver cirrhosis, WIT, BMI, and high preoperative FBG levels are risk factors for NODM, and age and preoperative IL-6 levels are independent risk factors. To a certain extent, higher BMI and poor hepatic function had reference significance for the incidence of NODM. Patients with a high concentration of FBG, IL-6, and TAC in the first month postoperatively had an increased risk of suffering from NODM.Keywords: liver transplantation, HBV, IL-6, immunosuppressants, NODM

Chronic hepatitis B virus (HBV) infection is a global public health problem, which can cause chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), and other diseases. Antiviral therapy is the most critical measure to slow down the progression of chronic hepatitis B, prevent or delay cirrhosis, HCC, and other kinds of liver decompensation events. At present, the anti-hepatitis B virus drugs are mainly nucleoside (acid) analogues (NAs) and interferon. Each kind of antiviral drug has different effects on the clinical outcome of hepatitis B patients (such as HCC). In this paper, we discussed the biological characteristics, natural course and prognosis of HBV infection, the mechanism of HBV-related HCC, the effect of different antiviral drugs on patients’ outcome, predictive biomarkers and model for HBV clinical outcome, predictors of sustained response and recurrence after withdrawal of antiviral therapy, consideration of expanding therapeutic indications and antiviral therapy, hoping to give a hand to the clinical diagnosis and treatment of HBV.

Non-Hodgkin lymphomas (NHL) are underestimated causes of cancer in West Africa where chronic viral hepatitis and HIV are endemic. While the association with HIV infection has already been characterized, limited information is available on the association between chronic viral hepatitis and NHL in sub-Saharan Africa. A case-control study was conducted in referral hospitals of Abidjan (Cote d’Ivoire) and Dakar (Senegal). Cases of NHL were matched with controls on age, gender and participating site. The diagnosis of NHL relied on local pathological examination completed with immunohistochemistry. HIV, HBV and HCV serology tests were systematically performed. A conditional logistic regression model estimated the associations by the Odds Ratio (OR) with their 95% confidence interval (CI). A total of 117 NHL cases (Abidjan n = 97, Dakar n = 20) and their 234 matched controls were enrolled. Cases were predominantly men (68.4%) and had a median age of 50 years (IQR 37-57). While Diffuse Large B-cell lymphoma were the most reported morphological type (n = 35) among mature B-cell NHL, the proportion mature T-cell NHL (30%) was high. The prevalence figures of HBV, HCV and HIV infection were 12.8%, 7.7% and 14.5%, respectively among cases of NHL. In multivariate analysis, HBV, HCV and HIV were independently associated with NHL with OR of 2.23 (CI 1.05-4.75), 4.82 (CI 1.52-15.29) and 3.32 (CI 1.54-7.16), respectively. Chronic viral hepatitis B and C were significantly associated with NHL in West Africa. Timely preventive measures against HBV infection and access to curative anti-HCV treatment might prevent a significant number of NHL.

Hepatitis B virus (HBV) is a blood-borne virus which is identified as a major etiological factor in acute and chronic liver disease, including liver cirrhosis and Hepato-cellular Carcinoma. Occult Hepatitis B Infection (OBI) is a form of infection where the patient or carrier of HBV is negative for HBsAg; the main serological screening test for HBV in clinical practice. OBI evades the current system of viral screening in Sudan, along with many other countries, raising the possibility for iatrogenic transmission of HBV infection. This study aims to identify the prevalence of OBI among patients with high risk of transmitting this infection in Sudan.

Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC50 = 0.28–0.42 µM), which was comparable to that of NVR 3-778 (EC50 = 0.38 µM). More importantly, the cytotoxicity of prodrug N8 (CC50 > 256 µM) was significantly reduced compared to NVR 3-778 (CC50 = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug N6 was hundreds of times better than that of NVR 3-778 in three phosphate buffers with various pH levels (2.0, 7.0, 7.4). In addition, N6 demonstrated excellent plasma and blood stability in vitro and good pharmacokinetic properties in rats. Finally, the hemisuccinate prodrug N6 significantly improved the candidate drug NVR 3-778’s water solubility and increased metabolic stability while maintaining its antiviral efficacy.

BackgroundPersons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US).MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals.ResultsWe identified 24 studies published between 1996–2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach).ConclusionsA very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Systematic review studying the survival outcomes with ICIs in phase III HCC clinical trials in context to HCC etiology (virus-driven or non-viral) and additional baseline characteristics.

Background & Aims HBV genotype G (HBV/G) is mainly found in co-infections with other HBV genotypes and was identified as an independent risk factor for liver fibrosis. This study aimed to analyse the prevalence of HBV/G co-infections in healthy European HBV carriers and to characterize the crosstalk of HBV/G with other genotypes. Methods A total of 560 European HBV carriers were tested via HBV/G-specific PCR for HBV/G co-infections. Quasispecies distribution was analysed via deep sequencing, and the clinical phenotype was characterized regarding qHBsAg-/HBV-DNA levels and frequent mutations. Replicative capacity and expression of HBsAg/core was studied in hepatoma cells co-expressing HBV/G with either HBV/A, HBV/D or HBV/E using bicistronic vectors. Results Although no HBV/G co-infection was found by routine genotyping PCR, HBV/G was detected by specific PCR in 4%-8% of patients infected with either HBV/A or HBV/E but only infrequently in other genotypes. In contrast to HBV/E, HBV/G was found as the quasispecies major variant in co-infections with HBV/A. No differences in the clinical phenotype were observed for HBV/G co-infections. In vitro RNA and DNA levels were comparable among all genotypes, but expression and release of HBsAg was reduced in co-expression of HBV/G with HBV/E. In co-expression with HBV/A and HBV/E expression of HBV/G-specific core was enhanced while core expression from the corresponding genotype was markedly diminished. Conclusions HBV/G co-infections are common in European inactive carriers with HBV/A and HBV/E infection, but sufficient detection depends strongly on the assay. HBV/G regulated core expression might play a critical role for survival of HBV/G in co-infections.

With the introduction of highly active antiretroviral treatment, HIV-related morbidity and mortality have declined. But underlying hepatitis B virus infection remains the major cause of AIDS-defined illness and liver-related disease progression mainly in endemic settings. Moreover, HBV–HIV co-infection is the leading cause of cirrhosis, hepatocellular carcinoma, and liver-related death. This review paper emphasizes reviewing the burden and impact of HBV–HIV co-infection in liver-related disease progression, immune recovery, and therapeutic management of HIV-infected individuals on ART regimen.

HIV testing is recommended at time of cancer diagnosis, HBV and HCV screening because of the risk of reactivation with certain anticancer drugs.This is a cross-sectional study. The objectives were to assess the screening practices in cancer patients and the satisfaction of professionals in the event of use of the CancerHIV network. A questionnaire drafted by the CancerHIV expert and the OncoPaca-Corse Regional Cancer Network (RCN) was distributed in the region at the end of 2018 (part 1: V1) before being extended to the national level via the CancerHIV network (part 2: V2). Participation reached 160 and 130 respondents (V1 and V2, respectively). At the initial cancer assessment, 23% of respondents declared that they systematically screened for HIV at V1 (V2: 17%), 25% for HBV (V2: 20%) and 24% for HCV (V2: 19%). Before immunotherapy, the rates were 54% for HIV in V1 (V2: 52%), 57% for HBV (V2: 60%) and 55% for HCV (V2: 57%). Among the respondents, satisfaction when requesting a regional or national remedy was high (almost 100%). Screening for HIV, HBV and HCV allows supervised prescription of immunosuppressive or cytotoxic treatment to a potentially immunosuppressed patient. This study, resulting of an original collaboration between a RCN and a national expert network, underlines the lack of screening at the 2 examined stages of patient care, and the need for raising practitioners' awareness to recommendations., Le dépistage de l’infection par le VIH est recommandé lors du bilan initial de tout cancer, celui de l’hépatite B et C en raison d’un risque de réactivation avec certains anticancéreux. Il s’agit d’une étude descriptive transversale. Les objectifs étaient d’évaluer les pratiques de dépistage chez des patients atteints de cancer et la satisfaction des professionnels en cas de recours au réseau CancerVIH. Un questionnaire élaboré par l’expert CancerVIH et le Réseau Régional de Cancérologie (RRC) OncoPaca-Corse a été diffusé fin 2018 en région (volet 1 : V1) avant une extension au niveau national via le réseau CancerVIH (volet 2 : V2). La participation a atteint 160 et 130 répondants (V1 et V2, respectivement). Au bilan initial de cancer, 23 % des répondants déclaraient dépister systématiquement le VIH au V1 (V2 : 17 %), 25 % le VHB (V2 : 20 %) et 24 % le VHC (V2 :19 %). Avant immunothérapie, les chiffres étaient de 54 % pour le VIH dans le V1 (V2 : 52 %), 57 % pour le VHB (V2 : 60 %) et 55 % pour le VHC (V2 : 57 %). Parmi les répondants, la satisfaction en cas de sollicitation du recours régional ou national était élevée (près de 100 %). Le dépistage du VIH, VHB et VHC permet la prescription encadrée d’un traitement immunosuppresseur ou cytotoxique à un patient potentiellement immunodéprimé. Cette enquête, fruit d’une collaboration originale entre RRC et réseau expert national, souligne l’insuffisance du dépistage aux 2 étapes de la prise en charge étudiées et la nécessité de sensibiliser les professionnels aux recommandations existantes.

We presented a case of hepatitis B virus (HBV)-related type III cryoglobulinemia vasculitis (CryoVas) characterized by extremity gangrene in a patient with diabetes. The 60-year-old female had a 10-year history of poorly controlled type 2 diabetes mellitus. She complained of sudden onset pain and swelling of toes which quickly progressed to gangrene, with fingers becoming pain and dark violet. The patient was initially misdiagnosed as diabetic foot (DF). Although DF is one of the common chronic complications of diabetes, it rarely involves the hand. What is more, the ischemic manifestations of the extremity were not consistent with the results of the vascular examination and immune system changes. The patient had Raynaud’s phenomenon, arthralgia, and extremity gangrene. Test results showed cryoglobulinemia multiple positive, polyclonal immunoglobulin with rheumatoid factor negative, lower complement 3, leukocytoclastic vasculitis, and HBV infection. HBV-related type III CryoVas was finally diagnosed, and a conservative therapy strategy was given. Six months after treatment with cyclophosphamide, corticosteroid, nucleoside/nucleotide analog therapy, local debridement, and dressing change, she recovered and kept no recurrence by following up for 30 months. To our knowledge, this is the first report of extremity gangrene caused by HBV-related CryoVas in a diabetic patient.

It is thought that chronic liver disease affects a person's risk of cardiovascular disease (CVD) development. The aim of this study was to assess the effect of Chronic Hepatitis B (HBV) infection, Chronic Hepatitis C (HCV) infection, and liver damage on cardiovascular risk and selected vascular parameters contributing to CVD risk. This case-control study included a group of 114 patients composed of 34 patients with HBV, 35 patients with HCV, and 45 patients as the control group. Cardiovascular risk was assessed by analyzing classic risk factors, and the SCORE system. The following arterial properties were analyzed using applanation tonometry with SphygmoCor Vx technology: central systolic blood pressure (cSBP), central pulse pressure, augmentation pressure, augmentation index, and carotid-femoral pulse wave velocity (PWV). Asymmetric dimethyloarginine (ADMA) blood levels were analyzed using ELISA as a marker of vascular function. In a univariable analysis we found no significant differences between the hepatitis B, hepatitis C, and control groups in terms of PWV (respectively: median 7.2 [Q25-Q75 6.4-8.5], 7.3 [6.9-8.7], 7.8 [6.5-8.9]), cSBP (115 [109-126], 118 [107-123], 116 [107-129]), ADMA (0.52 [0.47-0.60], 0.53 [0.45-0.62], 0.58 [0.51-0.63]), SCORE (0 [0-1], 0 [0-2], 0 [0-2]). No significant differences in cardiovascular variables were observed between cirrhotic and non-cirrhotic patients. A multivariable analysis confirmed the above findings. (PWV, p=0 . 29; cSBP, p=0.26; ADMA, p=0.19). We concluded that chronic hepatitis B or C was not independently associated with an adverse cardiovascular risk profile nor with an unfavorable pattern of vascular parameters contributing to CVD risk in our study population, even in the case of liver cirrhosis. The same was true for blood ADMA levels.

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow.

Objectives The biomarkers of an immunological dysregulation due to a chronic HBV infection are indeed understudied. If untreated, this condition may evolve into liver impairment co-occurring with extrahepatic involvements. Here, we aim to identify a new panel of biomarkers [including immunoglobulin G (IgG) subclasses, RF, and Free Light Chains (FLCs)] that may be useful and reliable for clinical evaluation of HBV-related cryoglobulinemia. Methods We retrospectively analysed clinical data from 44 HBV-positive patients. The patients were stratified (according to the presence/absence of mixed cryoglobulinemia) into two groups: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HDs) were used as negative controls. Serum samples were tested for IgG subclasses, RF (-IgM, -IgG, and -IgA type), and FLCs. Results We detected a strikingly different distribution of serum IgG subclasses between HDs and HBV-positive patients, together with different RF isotypes; in addition, FLCs were significantly increased in HBV-positive patients compared with HDs, while no significant difference was shown between HBV-positive patients with/without mixed cryoglobulinemia. Conclusion The immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open a new perspective in the precision medicine era; in these challenging times, they could also be employed to monitor the clinical course of those COVID-19 patients who are at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.

BACKGROUND The primary aspect of blood transfusion lies in the availability of blood and blood components which are tested and reported negative for transfusion transmitted infections (TTI’s). The increased seroprevalence of TTI’s indicate their prevalence in general public. The study was conducted to analyse the increasing seroprevalence of hepatitis C virus (HCV) over a period of 3 years. The objectives of the study determine the seroprevalence of hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) among the voluntary blood donors at a tertiary care hospital & associated blood bank. METHODS This cross-sectional study was done at the Department of Transfusion Medicine, GSVM Medical College, Kanpur, Uttar Pradesh, over a period of 3 years from July 2017 to June 2020. The samples collected were screened by enzyme-linked immunosorbent assay (ELISA) tests. RESULTS A total of 69561 blood units were collected during this 3-year study from July 2017 to June 2020. Of all the blood bags screened, the highest prevalence was seen for HBV followed by HCV and HIV. 949 (1.4 %) were reactive for HBV, 75 (0.1 %) were reactive for HIV and 332 (0.5 %) were reactive for HCV. The results show a remarkable increase in the seropositivity for hepatitis C infection. CONCLUSIONS The seroprevalence of HCV has seen an increase in case load over the years as compared to HBV and HIV. This increase in case volume is indicative of impending liver diseases progressing to chronic stage over the years. Thus, it is imperative to create awareness in the general population to help reduce the risk factors responsible for HCV infection. KEYWORDS Blood Transfusion, Voluntary Donors, HCV, HBV, HIV, Seroprevalence, Transfusion Transmitted Infections (TTI’s)

Hepatitis B surface antigen (HBsAg) seroclearance is regarded as the ideal endpoint for antiviral treatment. However, reports on the durability of and outcomes after HBsAg seroclearance are few, which has become a focus in clinical practice. This meta‐analysis was performed to evaluate the durability and hepatocellular carcinoma (HCC) incidence after HBsAg seroclearance after treatment cessation. We searched PubMed, Embase, Medline and Web of Science for studies that reported the durability and HCC incidence after HBsAg seroclearance published between 1 January 2000 and 31 January 2020. Data were analysed by a random‐effects model. Thirty‐eight studies and 43,924 patients were finally included. The results showed that HBsAg seroclearance was durable, with a pooled recurrence rate of 6.19% (95% CI: 4.10%–8.68%). There was no significant difference in recurrence rates after different seroclearance methods or among recurrence types and different regions. Anti‐HBs seroconversion resulted in a significantly reduced recurrence rate (RR = 0.25, p

HBV pol plays a critical role in the replication of hepatitis B virus (HBV). Previous studies conducted on HBV pol have produced limited evidence on HBV pol expression due to the lack of effective detection methods. The present study used the HBV pol (159–406 aa) protein as a target to screen for specific monoclonal antibodies that recognize HBV pol and subsequently evaluate their diagnostic and therapeutic value. Four antibodies (P3, P5, P12, P20) against HBV pol were obtained. Among them, the P20 antibody indicated optimal binding with HBV pol as demonstrated by Western blotting (WB) in a cell model transfected with the HBV genome. We also expressed P5 and P12 antibodies in mouse liver cells by transfection and the results indicated significant antiviral effects caused by these two antibodies especially P12. In summary, the present study established an antibody which was denoted P20. This antibody can be used to detect HBV pol expression by four HBV genomes via WB analysis. In addition, the antibody denoted P12 could exert antiviral effects via intracellular expression, which may provide a promising approach for the treatment of chronic hepatitis B.

The study aimed to evaluate the SWAT and HBV model’s responses to estimate streamflow in three typical selected watersheds in the upper Blue Nile Basin, Ethiopia. The evaluation was carried out through simulation of runoff in three watersheds, namely: Gilgel Abay, Anger, and Maybar located in the upper Blue Nile Basin, Ethiopia. The same calibration and validation period were applied for each watershed model with their respective historical records. The objective function indicates the optimized range of model parameters during the calibration and validation procedure, and it gives a good model response result, which is determined by the recommended performance indicators and hydrograph plots. The HBV and SWAT model’s calibration responds with (NSE = 0.81, NSE = 0.48 and NSE = 0.46) and (NSE = 0.81, NSE = 0.63, NSE = 0.61), respectively for Gilgel Abay, Anger, and Maybar watersheds. The optimized parameters were applied to validate the model using independent historical data. The SWAT and HBV model responses for NSE during the validation period were 0.8, 0.55, and 0.54 and 0.63, 0.45, and 0.34, respectively, for Gilgel Abay, Anger, and Maybe watersheds. An alternative was observed over and under estimation runoff during stimulation periods in extreme wet and dry periods. Generally, the calibrated and validated hydrograph output result indicates that the model’s responses to too wet and dry conditions were not satisfactory. Therefore, further model refinements for extreme events, including season-based model evaluations that could improve the process representation of rainfall-runoff events, are recommended.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and its specific mechanism has not been fully elucidated. Inactivation of tumor suppressors may contribute to the occurrence, progression, and recurrence of HCC. DNA methylation is a crucial mechanism involved in regulating the occurrence of HCC. Herein, we aimed to identify the key methylation-related tumor suppressors as well as potential biomarkers and therapeutic targets in HCC. Methods: Combined analysis of TCGA and GEO databases was performed to obtain potential methylation-related tumor suppressors in HCC. Methyl-target sequencing was performed to analyze the methylation level of the GNA14 promoter. The diagnostic value of GNA14 as a predictor of HCC was evaluated in HCC tumor samples and compared with normal tissues. The functional role of GNA14 and its upstream and downstream regulatory factors were investigated by gain-of-function and loss-of-function assays in vitro. Subcutaneous tumorigenesis, lung colonization, and orthotopic liver tumor model were performed to analyze the role of GNA14 in vivo. Results: The expression of GNA14 was found to be downregulated in HCC and it was negatively correlated with hepatitis B virus (HBV) infection, vascular invasion, and prognosis of HCC. DNA methylation was demonstrated to be responsible for the altered expression of GNA14 and was regulated by HBV-encoded X protein (HBx). GNA14 regulated the RB pathway by promoting Notch1 cleavage to inhibit tumor proliferation, and might inhibit tumor metastasis by inhibiting the expression of JMJD6. Conclusion: GNA14 could be regulated by HBx by modulating the methylation status of its promoter. We identified GNA14 as a potential biomarker and therapeutic target for HCC.

Hepatitis B virus (HBV) infection is a major public health problem. The high levels of HBV DNA and HBsAg are positively associated with the development of secondary liver diseases, including hepatocellular carcinoma (HCC). Current treatment with nucleos(t)ide analogues mainly reduces viral DNA, but has minimal, if any, inhibitory effect on the viral antigen. Although IFN reduces both HBV DNA and HBsAg, the serious associated side effects limit its use in clinic. Thus, there is an urgent demanding for novel anti‐HBV therapy. In our study, viral parameters were determined in the supernatant of HepG2.2.15 cells, HBV‐expressing Huh7 and HepG2 cells which transfected with HBV plasmids and in the serum of HBV mouse models with hydrodynamic injection of pAAV‐HBV1.2 plasmid. RT‐qPCR and Southern blot were performed to detect 35kb mRNA and cccDNA. RT‐qPCR, Luciferase assay and Western blot were used to determine anti‐HBV effects of MLN4924 and the underlying mechanisms. We found that treatment with MLN4924, the first‐in‐class neddylation inhibitor currently in several phase II clinical trials for anti‐cancer application, effectively suppressed production of HBV DNA, HBsAg, 3.5kb HBV RNA as well as cccDNA. Mechanistically, MLN4924 blocks cullin neddylation and activates ERK to suppress the expression of several transcription factors required for HBV replication, including HNF1α, C/EBPα and HNF4α, leading to an effective blockage in the production of cccDNA and HBV antigen. Our study revealed that neddylation inhibitor MLN4924 has impressive anti‐HBV activity by inhibiting HBV replication, thus providing sound rationale for future MLN4924 clinical trial as a novel anti‐HBV therapy.

International audience; Introduction: The implication of viruses in human cancers, as well as the emergence of next generation sequencing has permitted to investigate further their role and pathophysiology in the development of this disease. One such mechanism is the integration of portions of viral genomes in the human genome, as well as the specific action of viral oncogenes.inding integration sites and preserved oncogenes is still relying on heavy manual intervention. Methods: We developed an analysis and interpretation pipeline to determine viral insertions. Using data from directed viral capture, the pipeline conducts a crude genotyping phase to select reference viral genomes, identifies chimeric reads, extracts the putative human sequences to locate in the human reference genome, scores and ranks candidate junctions, and exports tabular and visual results. Results: We leverage common bioinformatics tools (bowtie2, samtools, blat), and a dedicated filtering and ranking algorithm, implemented in R, to infer candidate junctions and insertions. Static results (tables, figures) are produced, as well as an interactive interpretation tool developed as a shiny web app. Discussion: We validated this pipeline against published results of HPV, HBV, and AAV2 insertions and show good information retrieval.

IntroductionAn increase in migration rates to the European Union has been observed over the last few years. Part of these migrants is undocumented. This work aimed to describe the reported frequency of infectious diseases and their associated factors among unselected samples of undocumented migrants in France.MethodologyThe Premier Pas survey is a cross-sectional epidemiological survey of a random sample (two-stage sample design) conducted among undocumented migrants recruited in Paris and the Bordeaux region, in places and facilities likely to be frequented by undocumented migrants. The percentages were weighted. The analysis was performed using Stata 15.1 software.ResultsA total of 1,223 undocumented migrants were recruited from 63 places and facilities, with a participation rate of 50%. Most of them were between 30 and 40 years of age (36%), 69% were men, aged mainly 30–40 (36%) years old, from sub-Saharan Africa (60%) or North Africa (25%), and 60% had arrived ConclusionThis original study on a large random sample confirms the frequency of infectious diseases among undocumented migrants in France and the importance of integrating their screening during a health Rendezvous and their management into early access to care and inclusive medico-psycho-social management.

Hepatitis B testing is the gateway for prevention and care. However, previous studies document low hepatitis B testing uptake in sub-Saharan Africa. This study investigated knowledge, stigma endorsement and knowing someone with hepatitis B as correlates of hepatitis B testing behaviours among people in the Greater Accra and Northern regions of Ghana. A cross-sectional survey was completed by 971 participants (Greater Accra = 503, and Northern region = 468) between October 2018 and January 2019. Approximately 54% of the participants reported having been tested for hepatitis B. The logistic regression analyses showed that having greater hepatitis B knowledge was positively associated with hepatitis B testing (OR = 1.22, 95% CI: 1.14-1.30). Higher hepatitis B stigma endorsement was negatively related to hepatitis B testing (OR = 0.97, 95% CI: 0.96-0.99). Also, participants who knew someone (i.e. parent, sibling and/or friend) with hepatitis B were more likely to have tested compared to those who did not know someone with hepatitis B (OR = 7.15, 95% CI: 5.04-10.14). This study demonstrates that knowing someone with hepatitis B increases the likelihood of testing, highlighting the need to create safe and non-judgmental contexts for people with hepatitis B (PWHB) to disclose if they want to. Also, given that greater hepatitis B knowledge increases testing and hepatitis B stigma endorsement impedes testing, interventions that increase knowledge and reduce stigma should be incorporated in efforts to promote testing in Ghana.

Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T cells that bridge between innate and adaptive immunity. MALT cells act like a biliary firewall protecting the epithelial lining of the liver against pathogenic intruders. MAIT1 and MAIT17 subsets respond rapidly to pathogenic presence both in the liver as well as in the peripheral circulation. In addition to chronic hepatitis B virus (HBV) infection, MAIT cells also appear to serve as potential therapeutic targets in several other chronic ailments. Evidence indicates that MAIT cells have tissue repair functions also paving way for fibrotic changes during chronic HBV infection. Observations also suggest that HBV-hepatitis delta virus (HDV) co-infection disease progression is closely associated with loss of MAIT cells. Furthermore, reduction in the number of hepatic MAIT cells in patients with cirrhotic non-alcoholic fatty liver disease and HBV-associated primary liver cancer has also been reported. Given their concrete role against HBV disease progression, and has also become evident that the tumor microenvironment can cause functional impairment of MAIT cells. Here, we reviewed the protective and the pathological role of MAIT cells in chronic HBV infection and certain other related medical conditions based on the understanding that an optimal functioning of the MAIT cell arsenal is key to a "host-friendly" immune defense against HBV disease progression. Funding Agencies|Xiamen University Malaysia Research Funding (XMUMRF) [XMUMRF/2020-C5/ITCM/0003, XMUMRF/2018-C2/ILAB/0001]; Department of Science and Technology-Science and Engineering Research Board, Government of India [CRG/2019/006096]; Swedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; Swedish Society of Medicine; CALF

Hepatitis B virus (HBV) infection is the most prominent risk factor for developing hepatocellular carcinoma (HCC), which can increase the incidence of HCC by more than 100 times. Accumulated evidence has revealed that non-coding RNAs (ncRNAs) play a regulatory role in various tumors through the long non-coding RNA (lncRNA)–microRNA (miRNA)–mRNA regulation axis. However, the involvement of the ncRNA regulatory network in the progression of HBV infection-induced HCC remains elusive. In the current work, five tumor samples from patients with hepatitis B surface antigen (HBsAg)-positive HCC and three tumor samples from patients with HBsAg-negative HCC were collected for whole-transcriptome sequencing. Between the two groups, 841 lncRNAs, 54 miRNAs, and 1118 mRNAs were identified to be differentially expressed (DE). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that DE genes were mainly involved in cancer-related pathways, including Wnt and MAPK signaling pathways. The Gene Expression Omnibus (GEO) analysis further validated the selected DE mRNAs. The DE lncRNA–miRNA–mRNA network was built to explore the effect of HBV infection on the regulation of ncRNAs in HCC. These findings provide novel insights into the role of HBV infection in the progression of HCC.

Immune control of various infectious diseases, particularly viral, was shown to be more efficient for females than males. Response to viral vaccines (HAV, HBV) was higher in females. Data on hepatitis B virus (HBV) markers accumulated over 15 years in blood donors was stratified according to sex, including HBsAg, HBV viral load and levels of anti-HBs in areas where genotypes B and C (China), genotype D (Iran, Lebanon, Tunisia) and genotype E (Ghana, Burkina Faso, Gabon) were prevalent. HBsAg was screened by either ELISA or rapid tests, anti-HBc and anti-HBs by ELISA, HBV DNA load by a standardized method across sites. In Ghanaian children less than 5 years, HBV DNA load was significantly lower in females than in males (p = 0.035). In China, Ghana, Burkina Faso and Gabon blood donors, median HBsAg prevalence was ~5% and 3% in China, ~8.5% and 4.5% in Gabon, ~16% and 11% in Burkina Faso and ~11% and 7% in Ghana for male and female donors, respectively (p < 0.001). In HBsAg+ Ghanaian blood donors, distribution and median viral load were not significantly different between sexes; occult hepatitis B infections (OBI) were significantly more frequent in males. In Chinese blood donor anti-HBc+ and anti-HBs+, anti-HBs levels tended to be higher in males but vaccinated donors’ anti-HBs+ only, while anti-HBs levels were females > males. In areas where genotypes B-E are dominant, the prevalence of chronic HBV infection (HBsAg+) seems better controlled before age 16–18 by females infected vertically or horizontally. OBIs appear considerably more frequent in men, suggesting lower efficacy of HBV infection control. Female blood donors appear significantly safer from HBV than males, and their donation should be encouraged.

The Na+/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immunity, interferon-induced transmembrane proteins (IFITM) 1–3 have been characterized as virus entry-restricting factors for many viruses. The present study identified IFITM3 as a novel protein–protein interaction (PPI) partner of NTCP based on membrane yeast-two hybrid and co-immunoprecipitation experiments. Surprisingly, IFITM3 knockdown significantly reduced in vitro HBV infection rates of NTCP-expressing HuH7 cells and primary human hepatocytes (PHHs). In addition, HuH7-NTCP cells showed significantly lower HDV infection rates, whereas infection with influenza A virus was increased. HBV-derived myr-preS1 peptide binding to HuH7-NTCP cells was intact even under IFITM3 knockdown, suggesting that IFITM3-mediated HBV/HDV infection enhancement occurs in a step subsequent to the viral attachment to NTCP. In conclusion, IFITM3 was identified as a novel NTCP co-factor that significantly affects in vitro infection with HBV and HDV in NTCP-expressing hepatoma cells and PHHs. While there is clear evidence for a direct PPI between IFITM3 and NTCP, the specific mechanism by which this PPI facilitates the infection process remains to be identified in future studies.

Simple Summary Epidemiological data on viral hepatitis are essential to optimize screening programs. For HCV, the Italian Health Ministry planned a cohort screening for those born in 1969-1989. In order to update the epidemiological data of viral hepatitis in a highly endemic area of Southern Italy and assess whether the screening programs currently planned by the Italian government for those born between 1969-1989 will be effective, a retrospective multicenter study was carried out enrolling all COVID-19 hospitalized patients screened for markers of HCV and HBV infection. Indeed, the COVID-19 pandemic has resulted in access to the national health system of an unselected population similar to the general one. Among the 2126 patients evaluated, HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively. For HCV infection, a bimodal distribution was observed, with peaks in the birth cohorts 1930-1939 and 1960-1969 (11.6% and 5.6%, respectively). An analysis of the screening period imposed (born: 1969-1989) demonstrates that only 17% of HCV infection could be captured. Thus, an alignment of the screening period (i.e., birth cohort 1960-1984) would capture 40% of cases. Data show a high endemicity of hepatitis virus in our geographic area and the need for a tailored regional screening program. The COVID-19 pandemic led to the hospitalization of an unselected population with the possibility to evaluate the epidemiology of viral hepatitis. Thus, a retrospective multicenter study was conducted in an area of Southern Italy with the aim of assessing the prevalence of HCV and HBV markers and the ability of current screening program to capture cases. We evaluated 2126 hospitalized patients in seven COVID Centers of Naples and Caserta area in which 70% of the Campania population lives. HBsAg and HCV-Ab prevalence was 1.6% and 5.1%, respectively, with no differences between gender. Decade distribution for birth year shows a bimodal trend of HCV prevalence, with a peak (11.6%) in the decade 1930-1939 and a second peak (5.6%) for those born in 1960-1969. An analysis of the screening period imposed by the Italian government for those born between 1969 and 1989 shows that only 17% of cases of HCV infection could be captured. A small alignment of the screening period, i.e., those born from 1960 to 1984, would capture 40% of cases. The data confirm the high endemicity of our geographical area for hepatitis virus infections and underline the need for a tailored screening program according to the regional epidemiology.

The anti-hepatitis B virus (HBV) efficacy of baicalin (BA) is mediated by HBV-related hepatocyte nuclear factors (HNFs). However, this efficacy is severely limited by the low bioavailability of BA. Therefore, a novel liver-targeted BA liposome was constructed to promote the bioavailability and antiviral ability of BA. The results showed that apolipoprotein A1 (ApoA1)–modified liposomes (BAA1) significantly enhanced BA’s cellular uptake and specific distribution in the liver. Furthermore, the substantial inhibitory effects of BAA1 on HBsAg, HBeAg, HBV RNA, and HBV DNA were assessed in HB-infected cells and mice. Western blotting, co-immunoprecipitation, and transcriptomics analysis further revealed that the enhanced anti-HBV efficacy of BAA1 was attributed to the interaction between hepatocyte nuclear factors (HNFs) and estrogen receptors (ERs). Based on the findings, we propose that the ApoA1-modified liposomes aid BA in inhibiting HBV transcription and replication by augmenting its bioavailability and the HNFs–ERs axis.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight‐based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co‐infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro‐costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow‐up. SVR was achieved in 680/803 (84.6%) by intention‐to‐treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non‐PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real‐world estimate of $1250. High SVR rates were achieved for non‐PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real‐world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

Preventive or on-demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV-R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies. We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on-demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml. NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on-demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels

HBV-related liver sickness or hepatocellular carcinoma is common worldwide. Therefore, it is of interest to document the current trends in hepatitis prevention, diagnosis, treatment and care.

Viral hepatitis poses a serious threat to mankind. Hepatitis B and C Virus are blood borne pathogens that affect millions of individually globally. This study was conducted on a hospital-based population in Islamabad, Pakistan over a period of 4 months, utilizing ELISA as the diagnostic technique which suggested a higher seroprevalence rate for both HBV and HCV i.e. 2.07% and 8.24% respectively. A correlational analysis of the biochemical parameters of these individuals with HBV and HCV infection was carried out and the results indicated a positive correlation of HBV with Alkaline Phosphatase (ALP), HCV with Total Bilirubin (TBil) and both the viruses with Alanine Aminotransferase (ALT). Furthermore, the risk factors in relation to these viral infections were explored upon which our data suggested that surgery, blood transfusion and contact with contaminated instruments at the barber for haircut/shaving and jewelers for piercings were the major risk factors responsible for aiding the contraction of the viral disease by patients in the hospital. These high percentages of the viral infection among the population require proper management and prevention techniques to minimize the number of casualties and further cases to provide a healthier surrounding for the people to live in.

Background The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. Aim To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. Methods Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in two groups: low education level (less than high school) and high education level (completed high school or beyond). The association of demographic, etiological, and clinical stage of subjects with educational level was assessed using logistic regression analysis. In the analysis low educational level was the outcome variable. Results A total of 11,107 subjects born in Italy (mean age 55.5 years, sex ratio 1.5) were evaluated. Multiple logistic regression analysis shows that chronic HCV infection (O.R.1,38:95%,C.I.1.23-1.55), risky alcohol intake (O.R.1.96;95%,C.I.1.73-2.21) and liver cirrhosis (O.R.1.65;95%,C.I.1.46-1.85) all resulted independently associated with less than a completed high school education. HBV infection resulted independently associated with high education level (O.R.0.74;95%,C.I.0.64-0.86), reflecting changes in HBV modes of transmission in recent decades. No association was found with CLD related to non-alcoholic fatty liver disease (O.R.1.03;95%, C.I.0.81-1.30). Conclusions These findings show an independent association linking education level with viruses and alcohol-related CLD. Low educational level is associated with the severity of CLD.

The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

Background: The risk of mother to child transmission of hepatitis B virus (HBV) is recognized worldwide, a reason for which the World Health Organization aims to reduce this public health issue of major concern in the next ten years. The aim of our study was to detect circulating HBV genotypes in a selected population of pregnant women, as scientific evidence to recommend personalized antiviral therapy and to obtain updated epidemiological information. Methods: HBsAg positive pregnant women were selected by the National Institute of Public Health Romania. Blood samples were collected after signing the informed consent. The HBV genotypes were tested by INNO LiPA HBV genotyping method. Results. The D genotype was detected in 9/18 (50%) patients, genotype A in 3/18 (16.7%), and genotype F in 3/18 (16.7%) patients. Three patients had double infection, 11 had unique infection, and 4 had no detectable genotype. Conclusion. This study confirmed the results of previous studies regarding HBV genotype circulation in our country, with the mention that F genotype was a new one for our area. These data are useful from an epidemiological point of view and also for therapeutical reasons, as it is known that therapy should be genotype guided.

In this paper, we modify the HBV model proposed in [1] to include the spatial variations of free antibody, virus-antibody complexes, and free virus. By using comparison arguments and theory of uniform persistence, we can show that the persistene/extinction of HBV can be determined by the reproduction number(s).

The title compound, a new inhibitor of the Hepatitis B virus (HBV), was prepared via alkyl­ation of 3-(chloro­meth­yl)-5-(pentan-3-yl)-1,2,4-oxa­diazole in anhydrous dioxane in the presence of tri­ethyl­amine., The title compound, C15H22N4O5S, was prepared via alkyl­ation of 3-(chloro­meth­yl)-5-(pentan-3-yl)-1,2,4-oxa­diazole in anhydrous dioxane in the presence of tri­ethyl­amine. The thia­diazine ring has an envelope conformation with the S atom displaced by 0.4883 (6) Å from the mean plane through the other five atoms. The planar 1,2,4-oxa­diazole ring is inclined to the mean plane of the thia­diazine ring by 77.45 (11)°. In the crystal, mol­ecules are linked by C—H⋯N hydrogen bonds, forming chains propagating along the b-axis direction. Hirshfeld surface analysis and two-dimensional fingerprint plots have been used to analyse the inter­molecular contacts present in the crystal. Mol­ecular docking studies were use to evaluate the title compound as a potential system that inter­acts effectively with the capsid of the Hepatitis B virus (HBV), supported by an experimental in vitro HBV replication model.

The COVID-19 pandemic has forced us to direct most of the available resources towards its management. This has led to the neglect of all other pathologies, including cancer. The aim of this study was to verify whether the difficulty in accessing the health system has led to a reduction in new diagnoses of hepatocellular carcinoma (HCC) and whether this has already been reflected in a more advanced stage of the cancer. A single-center, retrospective study including adult patients with a new diagnosis of HCC was performed. Patients were divided into three groups: the prelockdown phase (May 2019–February 2020), the lockdown phase (March 2020–December 2020), and the postlockdown phase (January 2021–October 2021); 247 patients were included. The number of patients diagnosed with HCC distinctly diminished in the periods March 2020–December 2020 (n = 69; −35%) and January 2021–October 2021 (n = 72; −32%) as compared to the period May 2019–February 2020 (n = 106). Noteworthy was the reduced surveillance in the period January 2021–October 2021 as compared to May 2019–February 2020 (22.9% vs. 36.6%, p = 0.056). No significant changes have yet been observed in tumor characteristics (BCLC staging distribution remained unvaried, p = 0.665). In conclusion, the number of new HCC diagnoses decreased sharply in the first 2 years of the pandemic, with no worsening of the stage. A more advanced stage of the disease could be expected in the next few years in patients who have escaped diagnosis.

Funder: NIHR | NIHR Oxford Biomedical Research Centre, Funder: NIHR | NIHR Oxford Biomedical Research Centre (OxBRC), Hepatitis B virus (HBV) polymerase is divided into terminal protein, spacer, reverse transcriptase, and RNase domains. Spacer has previously been considered dispensable, merely acting as a tether between other domains or providing plasticity to accommodate deletions and mutations. We explore evidence for the role of spacer sequence, structure, and function in HBV evolution and lineage, consider its associations with escape from drugs, vaccines, and immune responses, and review its potential impacts on disease outcomes.

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV-D1 is the dominant subgenotype in the Mediterranean basin, Eastern Europe, and Asia. However, little is currently known about its evolutionary history and spatio-temporal dynamics. We use Bayesian phylodynamic inference to investigate the temporal history of HBV-D1, for which we calibrate the molecular clock using ancient sequences, and reconstruct the viral global spatial dynamics based, for the first time, on full-length publicly available HBV-D1 genomes from a wide range of sampling dates. We pinpoint the origin of HBV subgenotype D1 before the current era (BCE) in Turkey/Anatolia. The spatial reconstructions reveal global viral transmission with a high degree of mixing. By combining modern-day and ancient sequences, we ensure sufficient temporal signal in HBV-D1 data to enable Bayesian phylodynamic inference using a molecular clock for time calibration. Our results shed light on the worldwide HBV-D1 epidemics and suggest that this originally Middle Eastern virus significantly affects more distant countries, such as those in mainland Europe. ispartof: VIRUS EVOLUTION vol:8 issue:1 ispartof: location:England status: published