Hepatitis B virus-specific CD4 T cell responses differentiate functional cure from chronic surface antigen+ infection.

BACKGROUND & AIMS: With or without antiviral treatment, few individuals achieve sustained functional cure of chronic hepatitis B virus (HBV) infection. A better definition of what mediates functional cure is essential for improving immunotherapeutic strategies. We aimed to compare HBV-specific T cell responses in patients with different degrees of viral control. METHODS: We obtained blood from 124 HBV-infected individuals, including those with acute self-limiting HBV infection, chronic infection, and chronic infection with functional cure. We screened for HBV-specific T cell specificities by ELISpot, assessed the function of HBV-specific T cells using intracellular cytokine staining, and characterized HBV-specific CD4 T cells using human leukocyte antigen (HLA) class II tetramer staining, all directly ex vivo. RESULTS: ELISpot screening readily identified HBV-specific CD4 and CD8 T cell responses in acute resolving infection compared with more limited reactivity in chronic infection. Applying more sensitive assays revealed higher frequencies of functional HBV-specific CD4 T cells, but not CD8 T cells, in functional cure compared to chronic infection. Function independent analysis using HLA multimers also identified more HBV-specific CD4 T cell responses in functional cure compared to chronic infection, with the emergence of CD4 T cell memory both after acute and chronic infection. CONCLUSIONS: Functional cure is associated with higher frequencies of functional HBV-specific CD4 memory T cell responses. Thus, immunotherapeutic approaches designed to induce HBV functional cure should also aim to improve CD4 T cell responses. LAY SUMMARY: Immunotherapy is a form of treatment that relies on harnessing the power of an individual's immune system to target a specific disease or pathogen. Such approaches are being developed for patients with chronic HBV infection, in an attempt to mimic the immune response in patients who control HBV infection spontaneously, achieving a so-called functional cure. However, what exactly defines protective immune responses remains unclear. Herein, we show that functional cure is associated with robust responses by HBV-specific CD4 T cells (a type of immune cell).

Increase in Hepatitis A Cases Linked to Imported Strains to Rio de Janeiro, Brazil: A Cross-Sectional Study.

This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017-2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA was RT-PCR amplified and sequenced for further phylogenetic and phylogeographic analyses. From fifty-two HAV IgM+ individuals, most were men (78.85%; p = 0.024), aged 20-30 years old (84.61%; p < 0.001), resided in the Rio de Janeiro north zone (31/52; 59.62%; p = 0.001), and are men who have sex with men (MSM) (57.69%; p = 0.002). Sexual practices were more frequent (96%) than others risk factors (food-borne (44%), water-borne (42.31%), and parenteral (34.62%)). Individuals who traveled to endemic regions had a 7.19-fold (1.93-36.04; p < 0.01) increased risk of HAV. Phylogenetic analysis revealed four distinct clades of subgenotype IA, three of them comprised sequences from European/Asian MSM outbreaks and one from Brazilian endemic strains. Bayesian Inference showed that the imported strains were introduced to Brazil during large mass sportive events. Sexual orientation and sexual practices may play a role in acquiring HAV infection. Public policies targeting key populations must be implemented to prevent further dissemination of HAV and other STIs.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Recanalization after cerebral venous thrombosis. A randomized controlled trial of the safety and efficacy of dabigatran etexilate versus dose-adjusted warfarin in patients with cerebral venous and dural sinus thrombosis.

BACKGROUND: The effect of different anticoagulants on recanalization after cerebral venous thrombosis has not been studied in a randomized controlled trial. METHODS: RE-SPECT CVT (ClinicalTrials.gov number: NCT02913326) was a Phase III, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded endpoint adjudication. Acute cerebral venous thrombosis patients were allocated to dabigatran 150 mg twice daily, or dose-adjusted warfarin, for 24 weeks, after 5-15 days' treatment with unfractionated or low-molecular-weight heparin. A standardized magnetic resonance protocol including arterial spin labeling, three-dimensional time-of-flight venography, and three-dimensional contrast-enhanced magnetic resonance angiography was obtained at the end of the treatment period. Cerebral venous recanalization at six months was assessed by two blinded adjudicators, using the difference in a score of occluded sinuses and veins (predefined secondary efficacy endpoint) and in the modified Qureshi scale (additional endpoint), between baseline and the end of the treatment. RESULTS: Of 120 cerebral venous thrombosis patients randomized, venous recanalization could be evaluated in 108 (55 allocated to dabigatran and 53 to warfarin, 1 patient had a missing occlusion score at baseline). No patient worsened in the score of occluded cerebral veins and sinuses, while 33 (60%) on dabigatran and 35 (67%) on warfarin improved. The mean score change from baseline in the occlusion score was similar in the two treatment groups (dabigatran -0.8, SD 0.78; warfarin -1.0, SD 0.92). In the modified Qureshi score, full recanalization was adjudicated in 24 (44%) and 19 (36%), and partial recanalization in 23 (42%) and 26 (49%) patients in the dabigatran and warfarin arms, respectively. No statistically significant treatment difference in the modified Qureshi score could be detected (p = 0.44). CONCLUSION: The majority of patients with cerebral venous thrombosis, anticoagulated with either dabigatran or warfarin for six months, showed partial or complete recanalization of occluded sinuses and veins at the end of the treatment.Clinical trial registration: Trial registry name: ClinicalTrials.gov URL: https://clinicaltrials.gov Registration number: NCT02913326.

A Systematic Evaluation of IgM and IgG Antibody Assay Accuracy in Diagnosing Acute Zika Virus Infection in Brazil: Lessons Relevant to Emerging Infections.

Accurate diagnostics underpin effective public health responses to emerging viruses. For viruses, such as Zika virus (ZIKV), where the viremia clears quickly, antibody-based (IgM or IgG) diagnostics are recommended for patients who present 7 days after symptom onset. However, cross-reactive antibody responses can complicate test interpretation among populations where closely related viruses circulate. We examined the accuracy (proportion of samples correctly categorized as Zika positive or negative) for antibody-based diagnostics among Brazilian residents (Rio de Janeiro) during the ZIKV outbreak. Four ZIKV enzyme-linked immunosorbent assays (ELISAs; IgM and IgG Euroimmun, IgM Novagnost, and CDC MAC), two dengue ELISAs (IgM and IgG Panbio), and the ZIKV plaque reduction neutralization test (PRNT) were evaluated. Positive samples were ZIKV PCR confirmed clinical cases collected in 2015-2016 (n = 169); negative samples (n = 236) were collected before ZIKV was present in Brazil (≤2013). Among serum samples collected ≥7 days from symptom onset, PRNT exhibited the highest accuracy (93.7%), followed by the Euroimmun IgG ELISA (77.9%). All IgM assays exhibited lower accuracy (<75%). IgG was detected more consistently than IgM among ZIKV cases using Euroimmun ELISAs (68% versus 22%). Anti-dengue virus IgM ELISA was positive in 41.1% of confirmed ZIKV samples tested. The Euroimmun IgG assay, although misdiagnosing 22% of samples, provided the most accurate ELISA. Anti-ZIKV IgG was detected more reliably than IgM among ZIKV patients, suggesting a secondary antibody response to assay antigens following ZIKV infection. Antibody ELISAs need careful evaluation in their target population to optimize use and minimize misdiagnosis, prior to widespread deployment, particularly where related viruses cocirculate.

Non-adherence to Mediterranean diet and synergy with lifestyle habits in the occurrence of breast cancer: a case-control study in Italy.

OBJECTIVE: The aim of this study was to assess the synergistic effect of non-adherence to the Mediterranean Diet (MD) and lifestyle habits on the occurrence of breast cancer (BC). PATIENTS AND METHODS: A case-control study was carried out from September 2018 to February 2019 at the Teaching Hospital "Umberto I" in Rome. A Food Frequency Questionnaire was used for assessing the level of adherence to MD, the IPAQ Questionnaire to measure physical activity, and AUDIT-C to estimate alcohol consumption. The possible interaction between risk factors was tested using the synergism index. RESULTS: A total of 94 cases and 88 controls were enrolled (median age 55.8 for cases and 57.9 for controls). The MD Score over 6 was associated with low odds of having breast cancer (OR = 0.29; 95% CI: 0.12-0.69). There is a clear indication for the additivity and synergism between non-adherence to MD and many risk factors on the occurrence of BC: current smoker (S = 2.02; 95% CI 0.62-8.07), physical inactivity (S = 2.14; 95% CI 0.71 2-8.28) and alcohol consumption (S = 3.02; 95% CI 0.91-12.95). CONCLUSIONS: Primary prevention of BC can benefit from intervention targeting nutritional and lifestyle factors that act synergistically.

Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory.

T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Here we confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8+ T cells in human hepatitis C virus (HCV) infection before and after treatment. After viral cure, phenotypic changes in clonally stable exhausted T cell populations suggested differentiation toward a memory-like profile. However, functionally, the cells showed little improvement, and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for less time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved HCV infection. Thus, the duration of T cell stimulation impacts exhaustion recovery, with antigen removal after long-term exhaustion being insufficient for the development of functional T cell memory.

Results of the Italian project 'GiochiAMO' to improve nutrition and PA among children.

BACKGROUND: Prevalence of overweight and obesity during childhood is still elevated in high-income countries. GiochiAMO is a health promotion program that uses knowledge-based education and games to teach healthy nutrition and physical activity among children (6-8 years old). METHODS: This study was a single arm field trial. Second and third grade classes of primary school attended an oral presentation about nutrition and physical activity and then were involved in three game sessions. Two multiple-choice questionnaires were administered at the beginning and at the end of the trail. The following scores were measured: nutrition behavior score (NTs), physical activity behavior score (PAs) and delta score (Ds). Wilcoxon, T-test and Mann Whitney were used to perform the univariate analysis. RESULTS: A total number of 74 and 76 children participated in the physical activity and nutrition interventions. NTs was 4.17 (SD: 2.23) before and 5.03 (SD: 2.79) after the intervention (P = 0.005). PAs was 27.4 (SD: 9.6) before and 30.5 (SD: 10.7) after the intervention (P = 0.003). No significant differences were obtained comparing males and females for all scores. Ds was 0.86 for nutrition and 3.1 for physical activity. Univariate analysis of Delta scores obtained no significant differences. CONCLUSIONS: The present results confirm the effectiveness of 'GiochiAMO' to change nutrition and physical activity behavior.

Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory

T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards a memory-like profile. However, functionally, the cells showed little improvement and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics.

Evolution of the innate and adaptive immune response in women with acute Zika virus infection.

Zika virus (ZIKV) is a flavivirus that is closely related to other human pathogens, such as dengue virus (DENV)1. Primary transmission usually involves Aedes aegypti, which has expanded its distribution range considerably2, although rarer infection routes, including mother-to-fetus transmission, sexual contact and blood transfusion, have also been observed3-7. Primary ZIKV infection is usually asymptomatic or mild in adults, with quickly resolved blood viraemia, but ZIKV might persist for months in saliva, urine, semen, breast milk and the central nervous system8-12. During a recent ZIKV outbreak in South America, substantial numbers of neurological complications, such as Guillain-Barré syndrome, were reported13,14 together with cases of microcephaly and associated developmental problems in infants born to women infected with ZIKV during pregnancy15-20, highlighting the clinical importance of this infection. Analyses of the human immune response to ZIKV are lacking21-28, but the recent outbreak has provided an opportunity to assess ZIKV immunity using current immunological methods. Here, we comprehensively assess the acute innate and adaptive immune response to ZIKV infection in ten women who were recruited during early infection and followed through reconvalescence. We define a cascade of events that lead to immunological control of ZIKV, with previous exposure to DENV impacting some, but not all, mediators of antiviral immunity.

A systematic overview of the scientific literature on the association between Mediterranean Diet and the Stroke prevention.

BACKGROUND: Stroke is the most common cardiovascular disorder after heart disease and one of the major causes of death and disability. Mediterranean diet has proven to be an effective means to prevent cardiovascular diseases and may contribute to the prevention of stroke. This overview aims to analyze all reviews that examine the association between Mediterranean diet pattern and stroke. METHODS: We conducted a literature search on PubMed and Scopus databases, using the keywords "Mediterranean diet" and "Stroke". All studies were selected evaluating the association between the Mediterranean diet and the prevention of stroke and only systematic reviews, meta-analysis and narrative reviews were included. RESULT: 25 eligible articles were included (16 narrative reviews, 9 systematic reviews, 6 systematic reviews with meta-analyses). The authors stated that Mediterranean diet may be a useful means of preventing stroke, especially the 6 meta-analyses highlighted that high adherence to Mediterranean diet was protective against stroke, with a relative risk ranging from 0,64 (95% CI 0,48-0,88) to 0,90 (95% CI 0,87-0,93). Moderate adherence has not shown significant results. CONCLUSION: A high adherence to the Mediterranean diet is inversely associated with stroke risk, and can modify the costs of its management, therefore the prevention policies should implement adherence to this healthy diet.

Genetic Diversity of the Hepatitis B Virus Subgenotypes in Brazil.

Hepatitis B virus (HBV) subgenotypes may be related to clinical outcomes and response to antiviral therapy. Most Brazilian studies on HBV subgenotypes are restricted to some regions and to specific population groups. Here, we provide an insight about genetic diversity of HBV subgenotypes in 321 serum samples from all five geographical regions, providing a representative overview of their circulation among chronic carriers. Overall, HBV/A1 was the most prevalent subgenotype, being found as the major one in all regions except in South Brazil. Among HBV/D samples, subgenotype D3 was the most prevalent, found in 51.5%, followed by D2 (27.3%) and D4 (21.2%). D2 and D3 were the most prevalent subgenotypes in South region, with high similarity with European strains. D4 was found in North and Northeast region and clustered with strains from Cape Verde and India. For HBV/F, the most frequent subgenotype was F2 (84.1%), followed by F4 (10.1%) and F1 (5.8%), closely related with strains from Venezuela, Argentina and Chile, respectively. Phylogeographic analyses were performed using an HBV full-length genome obtained from samples infected with genotypes rarely found in Brazil (B, C, and E). According to Bayesian inference, HBV/B2 and HBV/C2 were probably introduced in Brazil through China, and HBV/E from Guinea, all of them mostly linked to recent events of human migration. In conclusion, this study provided a comprehensive overview of the current circulation of HBV subgenotypes in Brazil. Our findings might contribute to a better understand of the dynamics of viral variants, to establish a permanent molecular surveillance on the introduction and dispersion patterns of new strains and, thus, to support public policies to control HBV dissemination in Brazil.

A cross sectional study on the vocal handicap index applied to a sample of teachers in nurseries and primary school.

BACKGROUND: Acoustic pollution is generally analysed in relation to the risks for the hearing apparatus, omitting the extra-auditory effects, such as the damage that the noise can cause to the speaker's voice and listening to the learning of the vocal message. These damages are mainly found in school environments among teachers. OBJECTIVE: A cross-sectional study was carried out to verify the influence that the noise of the classrooms can have on the physical and mental health of the teachers examined. METHODS: This study involved four schools of Rome, for a total of 60 teachers, who were interviewed via online questionnaires, which consisted of a socio-demographic data section and 3 other sections: Vocal Handicap Index (VHI), SF-12, Job Content Questionnaire. RESULTS: 50 responses were received. 68% of teachers exceeded the normative value of 2.83 and perceived a disorder of the voice, and only 32% had a value lower than the standard considered (mean=7.34; median=5). The medians of MCS12 and PCS12 scores (52.9 and 54.2) were very close to those of the general population, as well as the distribution of the scores obtained from the Job Content Questionnaire. Furthermore, there was a direct association between the VHI-10 score and the age (B=0.321 p=0.016), the marital status (B=0.345 p= 0.009), and an indirect association with the MCS12 (B=-0.283 p=0.033). CONCLUSIONS: In general, the teachers examined are exposed in the classrooms to a high acoustic climate (median=75 dB) and, consequently, to a vocal effort during the didactic activities. Although it has not been possible to verify whether teachers with a high vocal disturbance were in the classrooms with a worse acoustic climate, the descriptive analyses provide a solid basis for further studies on the association between noise pollution and vocal effort.

Hepatitis A Strain Linked to the European Outbreaks During Gay Events between 2016 and 2017, Identified in a Brazilian Homosexual Couple in 2017.

Hepatitis A virus (HAV) outbreaks among men who have sex with men (MSM) have been reported worldwide and associated primarily with sexual transmission through oral-anal sex. Here, we provide the molecular and evolutionary description of a European strain, linked to HAV outbreaks among MSM, detected in a Brazilian homosexual couple. Bayesian analysis provided evidence that the viral isolates were introduced in Brazil from Spain between the end of 2016 and the beginning of 2017.

Accuracy of rapid test for diagnosis of hepatitis A with different infection rate settings and with predictive modeling.

AIM: We evaluated the accuracy of a commercial rapid immunochromatographic test (rapid test [RT]) for hepatitis A (HA) diagnosis and epidemiological studies. MATERIALS & METHODS: The accuracy of a RT was evaluated in laboratory and in field conditions. Predictive modeling estimated the test performance in a hypothetical population. RESULTS: The RT showed sensitivities of 66-86%, and specificities of 21-100%, depending on the antibody isotype (IgM or IgG) analyzed and prevalence of infection. CONCLUSION: The RT is a good alternative for diagnostic in HA outbreaks. The predictive model indicates that it should not be used alone for HA diagnosis in low prevalence populations. These data can be used in the future to strengthen decision-making during the implementation of rapid diagnostic methods in health services.

GnRH-agonist deslorelin implant alters the progesterone release pattern during early pregnancy in gilts.

The aim of this study was to investigate the relationship of progesterone (P) and luteinizing hormone (LH) during recognition and establishment of pregnancy in the gilt. Therefore, the effects of eliminating episodic LH pulses on P patterns were determined during early pregnancy. To this end, a slow-release GnRH implant deslorelin was used for GnRH down-regulation. A group of gilts (GnRHa, n = 8) was implanted with the GnRH-agonist on Day 11 of pregnancy, while a control group (C, n = 5) was treated with a non-impregnated placebo implant. Blood was collected via a vena cava caudalis catheter at 10-min intervals for 8 hr on Day 16 and 21 of pregnancy. As expected, the GnRH implant reduced LH secretion (p < 0.01) and abolished LH pulses completely at Day 16 and Day 21 of pregnancy. On Day 16, there was no difference in P levels between the treatments. However, on Day 21, the GnRH-agonist treatment led to significantly increased P concentrations (p < 0.01) compared with the control gilts. Progesterone was secreted in a pulsatile manner in both treatment groups and no relationship between LH pulsatility and P pulsatility was observed. In conclusion, abolishment of LH pulsatility did not affect the pulsatile pattern of P secretion but led to an unexpected overall increase in P on Day 21 of pregnancy; this effect was delayed and occurred 10 days after commencing treatment with the GnRH depot agonist. The elevation of P on Day 21 of pregnancy in the GnRHa group suggests either a reduced negative feedback effect or an increased autocrine response by the corpora lutea.

Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection.

OBJECTIVE: Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control. DESIGN: The phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection. RESULTS: We detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities. CONCLUSION: HBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure.

Returning to work after breast cancer: A systematic review of reviews.

BACKGROUND: Due to improvements in breast cancer diagnosis and treatment, the healthcare system faces a growing number of cancer survivors. Breast cancer survivors experience many difficulties when returning to work, including discrimination at work and lack of support by employers and colleagues. OBJECTIVE: To point out the knowledge in literature up to date about return to work (RTW) after breast cancer, the factors influencing it and the interventions to facilitate it. METHODS: A literature search was conducted in January 2017 using the databases Medline (PubMed) and Scopus. Studies were included if they analyzed the problem of RTW in women treated for breast cancer. RESULTS: Twenty-six articles met the inclusion criteria. The studies were divided into four themes: factors facilitating or impeding RTW; interventions to enhance RTW; lived experiences of RTW; economic aspects related to cancer survivors and RTW. CONCLUSIONS: The heterogeneity of the interventions suggests the need for a better definition of the concept of RTW. To compare interventions, studies should use a rigorous approach and better outcome measures should be identified to evaluate RTW.

Hepatitis D infection in Brazil: Prevalence and geographical distribution of anti-Delta antibody.

In Brazil, the Amazon Basin is endemic for hepatitis D virus (HDV) infection; however, studies in other regions of the country are scarce. This study aims to map the seroepidemiological situation of anti-Delta antibodies in chronic hepatitis B carriers in all five Brazilian geographic regions. Serum samples from 1240 HBsAg positive individuals (55.4% men; mean age 43.1 ± 13.4 years) from 24 of 26 Brazilian states were tested for the presence of anti-Delta antibodies using a commercial immunoassay. Anti-Delta antibodies were detected in 40 samples (3.2%; 52.5% female; mean age of 38.1 ± 13.8 years). Age less than 20 years was significantly associated with anti-HDV positivity (P < 0.001). The distribution of anti-Delta differed markedly in the diverse regions of the country. The highest prevalence of anti-HDV was found in the North (8.5%; P < 0.001), followed by Central West (2.5%), Southeast (1.7%), Northeast (0.8%), and South (0.0%). Anti-Delta antibodies were detected in 12 states, but more than 60% of the positive cases were observed in two states, Amazonas and Acre, located in the western portion of the Amazon region. The overall HDV prevalence of 3.2% emphasizes that HDV is far from being a disease under control in Brazil. Despite the low HDV prevalence in non-endemic regions, this infection persists as a major concern in two states (Acre and Amazonas) in the north of the country, indicating that a continuous epidemiological surveillance program should be implemented in all Brazilian regions.