RESUMEN
Hepatitis Delta Virus (HDV), a satellite virus of Hepatitis B virus, exacerbates liver damage in affected individuals. Screening for HDV antibodies in HBsAg positive patients is recommended, but the diagnostic accuracy of serological tests remains uncertain. This review aimed to assess the diagnostic accuracy of serological tests for HDV. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Scopus etc. for relevant studies. Studies measuring the sensitivity and specificity of serological HDV tests against PCR as a reference standard were included. Pooled sensitivity and specificity for each test method and sero-marker were calculated. The review included six studies with 11 study arms, evaluating ARCHITECT immunoassay, EIA, ELISA, QMAC, RIA, and Western Blot test methods targeting Anti-HDV IgG, Total anti-HDV and Anti-HDV IgM. Sensitivities for Anti-HDV IgG, Total Anti-HDV and Anti-HDV IgM, tests were 97.4%, 51.9%, and 62.0%, respectively, with specificities of 95.3%, 80.0%, and 85.0%. Our findings, with its limited number of studies, suggest that HDV serological tests, particularly those identifying Anti IgG exhibit high accuracy and can serve as effective screening tools for HDV.
Asunto(s)
Hepatitis D , Virus de la Hepatitis Delta , Sensibilidad y Especificidad , Pruebas Serológicas , Humanos , Virus de la Hepatitis Delta/inmunología , Hepatitis D/diagnóstico , Hepatitis D/virología , Hepatitis D/sangre , Hepatitis D/inmunología , Pruebas Serológicas/métodos , Pruebas Serológicas/normas , Inmunoglobulina G/sangre , Anticuerpos Antihepatitis/sangre , Inmunoglobulina M/sangreRESUMEN
Viral hepatitis are infections that can cause liver damage, become chronic, lead to cirrhosis, hepatocellular carcinoma and ultimately result in death due to their ability to spread in the community through blood and infected body fluids. The aim of this study was to determine the seroprevalence of hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) transmitted through blood among individuals living in Trabzon province and to examine the factors potentially associated with seroprevalence. This cross-sectional study was conducted in Trabzon province, located in the northeast of Türkiye, including a total of 10 districts, including the central district. Since seroprevalence was calculated for HBV, HCV, and HDV in the study, the sample size was separately calculated for each, and the calculated maximum sample size of 1116 was accepted as the minimum sample size for the study. The study was completed with 1502 participants. Serological tests for HBV included HBsAg, anti-HBs, and anti-HBc IgG; for HCV, anti-HCV; and for HDV, anti-HDV were analysed. Data were evaluated for HBV risk factors using univariate analyses with Chi-square test and for multiple analyses using enter model logistic regression analysis. The mean age of the participants was 45.7 ± 16.6 years, with 767 (51.1%) being female. The prevalence of HBV seropositivity, indicating vaccination, was 23.0%, while the seroprevalence of HBV among unvaccinated adults was 27.4%. HBsAg positivity was 5.1%, and isolated anti-HBc IgG positivity was 4.2%. The proportion of individuals with HBsAg in the gray zone was 0.5%, while the positivity rates for anti-HBs and anti-HBc IgG (indicating past infection) were 17.6%. The prevalence of anti-HCV was six per thousand, while anti-HDV was not detected in the analyses. HBsAg positivity and co-infection with HCV were found in one person, and among the nine individuals positive for anti-HCV, isolated anti-HBc IgG positivity was detected in three. Increasing age, presence of a person with jaundice in the family, presence of diabetes mellitus, alcohol use and cupping therapy were identified as risk factors for HBV in the logistic regression analysis. Risk factors for HCV in univariate analyses were being over 40 years old, presence of hepatic steatosis and receiving dialysis treatment. The results of the study indicate that despite being included in our vaccination schedule and the administration of vaccines to high-risk adults, HBV still requires intensive attention as a public health problem. HCV, lacking a vaccine has been evaluated as an infectious agent that needs to be taken into consideration due to its potential risks and requires the complete implementation of individual and social precautions.
Asunto(s)
Antígenos de Superficie de la Hepatitis B , Hepatitis B , Hepatitis C , Hepatitis D , Humanos , Estudios Seroepidemiológicos , Hepatitis D/epidemiología , Hepatitis D/inmunología , Factores de Riesgo , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Adulto , Hepatitis C/epidemiología , Hepatitis B/epidemiología , Turquía/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Modelos Logísticos , Anciano , Anticuerpos contra la Hepatitis B/sangre , Adulto Joven , Anticuerpos contra la Hepatitis C/sangre , Adolescente , Anticuerpos Antihepatitis/sangreRESUMEN
The pathogenesis of viral infection is attributed to two folds: intrinsic cell death pathway activation due to the viral cytopathic effect, and immune-mediated extrinsic cellular injuries. The immune system, encompassing both innate and adaptive immunity, therefore acts as a double-edged sword in viral infection. Insufficient potency permits pathogens to establish lifelong persistent infection and its consequences, while excessive activation leads to organ damage beyond its mission to control viral pathogens. The innate immune response serves as the front line of defense against viral infection, which is triggered through the recognition of viral products, referred to as pathogen-associated molecular patterns (PAMPs), by host cell pattern recognition receptors (PRRs). The PRRs-PAMPs interaction results in the induction of interferon-stimulated genes (ISGs) in infected cells, as well as the secretion of interferons (IFNs), to establish a tissue-wide antiviral state in an autocrine and paracrine manner. Cumulative evidence suggests significant variability in the expression patterns of PRRs, the induction potency of ISGs and IFNs, and the IFN response across different cell types and species. Hence, in our understanding of viral hepatitis pathogenesis, insights gained through hepatoma cell lines or murine-based experimental systems are uncertain in precisely recapitulating the innate antiviral response of genuine human hepatocytes. Accordingly, this review article aims to extract and summarize evidence made possible with bona fide human hepatocytes-based study tools, along with their clinical relevance and implications, as well as to identify the remaining gaps in knowledge for future investigations.
Asunto(s)
Virus de la Hepatitis Delta , Hepatocitos , Inmunidad Innata , Interferones , Receptores de Reconocimiento de Patrones , Humanos , Hepatitis D/inmunología , Hepatitis D/virología , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/fisiología , Hepatocitos/virología , Hepatocitos/inmunología , Interacciones Huésped-Patógeno/inmunología , Interferones/inmunología , Interferones/metabolismo , Moléculas de Patrón Molecular Asociado a Patógenos/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Receptores de Reconocimiento de Patrones/inmunologíaRESUMEN
BACKGROUND: HDV antibody testing is recommended for universal screening and as the first line in an HDV double reflex testing strategy for effectively identifying patients with active infection for therapeutic treatments. OBJECTIVE: The aim of this study is to evaluate the performance of a newly developed ARCHITECT HDV Total Ig (ARCHITECT HDV Ig) prototype assay. STUDY DESIGN: Performance characteristics were determined for the ARCHITECT HDV Ig and a reference test, LIAISON XL Anti-HDV using a well-characterized specimen panel, comprising HDV RNA positive (n = 62) and negative (n = 70) samples, and healthy US blood donors. RESULTS: Healthy US blood donors (n=200) showed 99.5% (199/200, 95%CI=97.65-99.98) specificity with ARCHITECT HDV Ig and 98.5 % (197/200, 95 %CI = 96.10-99.64) with LIAISON Anti-HDV. Among known HDV RNA positive samples, ARCHITECT HDV Ig detected 59/62 demonstrating 95.2 % sensitivity while LIAISON Anti-HDV sensitivity was 90.3 % (56/62). Among 101 HBV positive samples, 70 were reactive in the ARCHITECT test, 59 of which tested positive for HDV RNA for a positive predictive value (PPV) for the presence of HDV RNA was 84.3 %. For LIAISON Anti-HDV, 79 specimens were reactive and 56 contained HDV RNA: PPV for HDV RNA was 70.9 %. Among 70 HDV RNA negative samples, 39 were HBV positive. ARCHITECT HDV Ig negative predictive value (NPV) was 71.8 % and LIAISON Anti-HDV NPV was 41 % for the HBV positive group, respectively. CONCLUSION: When compared to the LIASON Anti-HDV test, the ARCHITECT HDV Ig assay demonstrated enhanced sensitivity and specificity and better NPV and PPV values for HDV RNA status. The ARCHITECT HDV Ig assay represents a promising tool for universal screening of all HBsAg-positive persons.
Asunto(s)
Anticuerpos Antihepatitis , Hepatitis D , Virus de la Hepatitis Delta , Ensayos Analíticos de Alto Rendimiento , Sensibilidad y Especificidad , Humanos , Hepatitis D/diagnóstico , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/aislamiento & purificación , Anticuerpos Antihepatitis/sangre , Ensayos Analíticos de Alto Rendimiento/métodos , Pruebas Serológicas/métodos , Automatización de Laboratorios/métodos , Donantes de SangreRESUMEN
With the increasing momentum and success of monoclonal antibody therapy in conventional medical practices, there is a revived emphasis on the development of monoclonal antibodies targeting the hepatitis B surface antigen (anti-HBs) for the treatment of chronic hepatitis B (HBV) and hepatitis D (HDV). Combination therapies of anti-HBs monoclonal antibodies, and novel anti-HBV compounds and immunomodulatory drugs presenting a promising avenue to enhanced therapeutic outcomes in HBV/HDV cure regimens. In this review, we will cover the role of antibodies in the protection and clearance of HBV infection, the association of anti-HBV surface antigen antibodies (anti-HBs) in protection against HBV and how antibody effector functions, beyond neutralization, are likely necessary. Lastly, we will review clinical data from previous and ongoing clinical trials of passive antibody therapy to provide a state-of-the-are perspective on passive antibody therapies in combinations with additional novel agents.
Asunto(s)
Hepatitis D , Inmunización Pasiva , Humanos , Hepatitis D/inmunología , Hepatitis D/tratamiento farmacológico , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Anticuerpos contra la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Animales , Antígenos de Superficie de la Hepatitis B/inmunología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/inmunología , Hepatitis B/inmunología , Hepatitis B/prevención & control , Hepatitis B/tratamiento farmacológico , Antivirales/uso terapéutico , Virus de la Hepatitis Delta/inmunologíaRESUMEN
The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher's exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) did not have hepatitis B immunity, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.
Asunto(s)
Hepatitis B , Hepatitis D , Tamizaje Masivo , Humanos , Femenino , Masculino , Philadelphia/epidemiología , Hepatitis B/prevención & control , Hepatitis B/epidemiología , Hepatitis B/inmunología , Adulto , Persona de Mediana Edad , Hepatitis D/epidemiología , Hepatitis D/diagnóstico , Hepatitis D/inmunología , Prevalencia , Consumidores de Drogas/estadística & datos numéricos , Factores de Riesgo , Adulto Joven , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangreRESUMEN
The hepatitis delta virus (HDV) is the smallest known human virus, yet it causes great harm to patients co-infected with hepatitis B virus (HBV). As a satellite virus of HBV, HDV requires the surface antigen of HBV (HBsAg) for sufficient viral packaging and spread. The special circumstance of co-infection, albeit only one partner depends on the other, raises many virological, immunological, and pathophysiological questions. In the last years, breakthroughs were made in understanding the adaptive immune response, in particular, virus-specific CD4+ and CD8+ T cells, in self-limited versus persistent HBV/HDV co-infection. Indeed, the mechanisms of CD8+ T cell failure in persistent HBV/HDV co-infection include viral escape and T cell exhaustion, and mimic those in other persistent human viral infections, such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), and HBV mono-infection. However, compared to these larger viruses, the small HDV has perfectly adapted to evade recognition by CD8+ T cells restricted by common human leukocyte antigen (HLA) class I alleles. Furthermore, accelerated progression towards liver cirrhosis in persistent HBV/HDV co-infection was attributed to an increased immune-mediated pathology, either caused by innate pathways initiated by the interferon (IFN) system or triggered by misguided and dysfunctional T cells. These new insights into HDV-specific adaptive immunity will be discussed in this review and put into context with known well-described aspects in HBV, HCV, and HIV infections.
Asunto(s)
Hepatitis D/inmunología , Virus de la Hepatitis Delta/fisiología , Inmunidad Adaptativa , Animales , Linfocitos T CD8-positivos/inmunología , Hepatitis D/virología , Virus de la Hepatitis Delta/genética , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/patogenicidad , Humanos , Evasión Inmune , Replicación ViralRESUMEN
Objective: To investigate the sero-epidemiological characteristics of the hepatitis D virus (HDV) infection among hepatitis B virus (HBV)-infected patients in Xinjiang region. Methods: A single-center cross-sectional analysis method was used to select 264 cases of hepatitis B virus infection who were hospitalized in the Center for Infectious Diseases and Liver Diseases of the First Affiliated Hospital of Xinjiang Medical University from August 2021 to January 2022. All patients were tested for HDV Ag, HDV IgM, HDV IgG, and HDV RNA. The infection status of hepatitis D virus was analyzed by grouping according to their clinical type, HBV viral load, and HBsAg level. A paired t-test was used for data with measurement data conforming to normal distribution. A paired rank sum test was used for data that did not conform to normal distribution before and after treatment. Results: A total of 36 cases (13.64%) and 26 cases (9.85%) were positive for HDV serological markers and HDV RNA. According to clinical type grouping, the positive rates of HDV serum markers in patients with chronic hepatitis B, hepatitis B-related cirrhosis, liver cancer, and liver failure were 13.46%, 12.43%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=0.86, P=0.649). The positive rates of HDV RNA were 11.54%, 8.11%, and 20.83%, respectively, and there was no statistically significant difference among the three groups (χ2=4.015, P=0.134). According to HBV viral load grouping, the positive rates of HDV serum markers among patients with viral loads <20, 20-2 000, and >2 000 IU/ml were 17.15%, 7.81%, and 6.67%, respectively, and the difference was not statistically significant among the three groups (χ2=4.846, P=0.089). The positive rates of HDV RNA were 9.47%, 10.94%, and 10%, respectively, and the difference was not statistically significant among the three groups (χ2=0.113, P=0.945). According to HBsAg level grouping, the positive rates of HDV serum markers in HBsAg<0.05, 0.05~250, and >250 IU/ml were 14.29%, 16.67%, and 10.85%, respectively, and there was no statistically significance between the three groups (χ2=1.745, P=0.418). The positive rates of HDV RNA were 4.76%, 8.77%, and 11.63%, respectively, and there was no statistically significant difference among the three groups (χ2=1.221, P=0.543). Clinical outcome, disease course, HBV DNA, serological markers of viral hepatitis, routine blood test, biochemical indicators, coagulation function, and other laboratory indicators were compared between HDV serum marker and/or nucleic acid positive and negative patients, and there was no statistically significant difference (P>0.05). Conclusion: The positive rate of HDV serological markers and HDV RNA is 13.64% and 9.85%, respectively, at a single center in the Xinjiang region, and there is still a high HDV infection rate among the HBV-infected patients with low levels of viral load and HBsAg.
Asunto(s)
Hepatitis B , Hepatitis D , Humanos , Biomarcadores/sangre , Estudios Transversales , Pruebas Hematológicas , Anticuerpos Antihepatitis/sangre , Anticuerpos Antihepatitis/inmunología , Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Hepatitis D/sangre , Hepatitis D/epidemiología , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , China/epidemiología , Carga Viral , Antígenos de la Hepatitis/sangre , Antígenos de la Hepatitis/inmunología , Estudios Seroepidemiológicos , ARN Viral/sangre , ARN Viral/inmunologíaRESUMEN
Approximately 70 million humans worldwide are affected by chronic hepatitis D, which rapidly leads to liver cirrhosis and hepatocellular carcinoma due to chronic inflammation. The triggers and consequences of this chronic inflammation, induced by co-infection with the hepatitis D virus (HDV) and the hepatitis B virus (HBV), are poorly understood. Using CRISPR technology, we characterized the recognition of HDV mono- and co-infection by intracellular innate immunity and determined its influence on the viral life cycle and effector T-cell responses using different HBV and HDV permissive hepatoma cell lines. We showed that HDV infection is detected by MDA5 and -after a lag phase -induces a profound type I interferon response in the infected cells. The type I interferon response, however, was not able to suppress HDV replication or spread, thus providing a persistent trigger. Using engineered T-cells directed against the envelope proteins commonly used by HBV and HDV, we found that HDV immune recognition enhanced T-cell cytotoxicity. Interestingly, the T-cell effector function was enhanced independently of antigen presentation. These findings help to explain immune mediated tissue damage in chronic hepatitis D patients and indicate that combining innate triggers with T-cell activating therapies might allow for a curative approach.
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Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Inmunidad Innata , Linfocitos T Citotóxicos/inmunología , Presentación de Antígeno/inmunología , Línea Celular Tumoral , Humanos , Interferón Tipo I/metabolismo , Helicasa Inducida por Interferón IFIH1/metabolismo , Receptores de Reconocimiento de Patrones/metabolismo , Replicación ViralRESUMEN
Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring the hepatitis B surface antigen (HBsAg) for its replication with approximately 10-70 million persons infected. Elimination of hepatitis D is, therefore, closely tied to hepatitis B elimination. There is a paucity of quality data in many resource-poor areas. Despite its aggressive natural history, treatment options for hepatitis D to date have been limited and, in many places, inaccessible. For decades, Pegylated interferon alpha (Peg IFN α) offered limited response rates (20%) where available. Developments in understanding viral replication pathways has meant that, for the first time in over three decades, specific therapy has been licensed for use in Europe. Bulevirtide (Hepcludex®) is an entry inhibitor approved for use in patients with confirmed viraemia and compensated disease. It can be combined with Peg IFN α and/or nucleos(t)ide analogue for hepatitis B. Early reports suggest response rates of over 50% with good tolerability profile. Additional agents showing promise include the prenylation inhibitor lonafarnib, inhibitors of viral release (nucleic acid polymers) and better tolerated Peg IFN lambda (λ). These agents remain out of reach for most resource limited areas where access to new therapies are delayed by decades. strategies to facilitate access to care for the most vulnerable should be actively sought by all stakeholders.
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Hepatitis D/tratamiento farmacológico , Hepatitis D/inmunología , Antivirales/uso terapéutico , Quimioterapia Combinada , Europa (Continente) , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Humanos , Interferón-alfa/uso terapéutico , Lipopéptidos , Piperidinas , Piridinas , Resultado del Tratamiento , Carga Viral , Replicación ViralRESUMEN
HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.
Asunto(s)
Hepacivirus/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis D/epidemiología , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , China/epidemiología , Coinfección/epidemiología , Coinfección/virología , Alemania/epidemiología , Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis B/inmunología , Humanos , ARN Viral/sangre , Estudios Retrospectivos , Estudios SeroepidemiológicosRESUMEN
Approximately 5% of individuals infected with hepatitis B virus (HBV) are coinfected with hepatitis D virus (HDV). Chronic HBV/HDV coinfection is associated with an unfavourable outcome, with many patients developing liver cirrhosis, liver failure and eventually hepatocellular carcinoma within 5-10 years. The identification of the HBV/HDV receptor and the development of novel in vitro and animal infection models allowed a more detailed study of the HDV life cycle in recent years, facilitating the development of specific antiviral drugs. The characterisation of HDV-specific CD4+ and CD8+T cell epitopes in untreated and treated patients also permitted a more precise understanding of HDV immunobiology and possibly paves the way for immunotherapeutic strategies to support upcoming specific therapies targeting viral or host factors. Pegylated interferon-α has been used for treating HDV patients for the last 30 years with only limited sustained responses. Here we describe novel treatment options with regard to their mode of action and their clinical effectiveness. Of those, the entry-inhibitor bulevirtide (formerly known as myrcludex B) received conditional marketing authorisation in the European Union (EU) in 2020 (Hepcludex). One additional drug, the prenylation inhibitor lonafarnib, is currently under investigation in phase III clinical trials. Other treatment strategies aim at targeting hepatitis B surface antigen, including the nucleic acid polymer REP2139Ca. These recent advances in HDV virology, immunology and treatment are important steps to make HDV a less difficult-to-treat virus and will be discussed.
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Hepatitis D/terapia , Virus de la Hepatitis Delta/inmunología , Inmunidad Adaptativa , Animales , Hepatitis D/inmunología , Hepatitis D/virología , Hepatitis D Crónica/inmunología , Hepatitis D Crónica/terapia , Hepatitis D Crónica/virología , Virus de la Hepatitis Delta/genética , Humanos , Inmunidad InnataAsunto(s)
Antivirales/uso terapéutico , Hepatitis D/tratamiento farmacológico , Virus de la Hepatitis Delta , Interferón-alfa/uso terapéutico , Antivirales/efectos adversos , Quimioterapia Combinada , Antígenos de Superficie de la Hepatitis B/biosíntesis , Hepatitis D/inmunología , Hepatocitos/metabolismo , Humanos , Interferón-alfa/efectos adversosRESUMEN
INTRODUCTION: Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV). An estimated 5% of HBV infected individuals worldwide have HDV infection. There is paucity of studies in Nigeria on the burden of HDV infection. This study aimed at determining the prevalence rate of HDV antibodies among individuals with chronic hepatitis B (CHB) infection and comparing the liver function test (LFT) and disease severity among the anti-HDV positive (anti-HDV+) and anti-HDV negative (anti-HDV-) individuals. METHODOLOGY: A cross-sectional study of 180 CHB infected individuals who were clinically evaluated and tested for HDV antibodies using the Enzyme-linked Immunoassay method. Their LFT profile and Child-Turcotte-Pugh (CTP) were also assessed. Data were analyzed using the SPSS version 17. RESULTS: Their mean age was 35.2 ± 10.4 years. There were 150 (83.3%) and 30 (16.7%) individuals with uncomplicated and complicated CHB infection respectively. Thirty-four (18.9%) of the participants were anti-HDV+. The mean serum ALT, AST, albumin and INR of the anti-HDV+ subjects were 16.5 ± 13.8 IU/L, 26.3 ± 32.6 IU/L, 38.9 ± 7.6 g/L, and 1.2 ± 0.2 respectively. The mean values for the same parameters of the anti-HDV- subjects were 10.8 ± 9.5 IU/L, 13.4 ± 11.2 IU/L, 41.4 ± 6.0 g/L and 1.1 ± 0.2 respectively (p < 0.05). The mean CTP scores in the anti-HDV+ and anti-HDV- subjects were 6.1 ± 2.1 and 5.5 ± 1.2 respectively (p= 0.03). CONCLUSIONS: Anti-HDV sero-prevalence rate was 18.9% and anti-HDV+ CHB patients had worse LFT results compared to those who were anti-HDV-.
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Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/inmunología , Hepatitis D/complicaciones , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Adulto , Estudios Transversales , Femenino , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/virología , Hepatitis D/epidemiología , Hepatitis D/virología , Humanos , Hígado/fisiopatología , Hígado/virología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
The treatment for hepatitis Delta virus (HDV) still consists of Pegylated interferon (PEG-IFN) combined with inhibitors of Hepatitis B virus (HBV) replication. In some patients may be occur a virological response, which means a negative HDV RNA 6 months after stopping treatment. In this study it was conducted an in vitro approach with the aim to mimic possible immunological events that are observed in patients responding to PEG-IFN therapy. Jurkat cells (human T lymphocyte cell line) were employed alone or co-cultured with THP-1 (human monocytic cell line) and stimulated with controls and HBV Surface Antigen (HBsAg), Small-Delta Antigen (SHDAg), and HBsAg + SHDAg combined. Twenty-four hours stimulation with SHDAg and/or HBSAg led to a toxic profile in a co-culture condition and cell supernatants were collected for cytokines quantification. PEG-IFN was added and cells were incubated for additional 24 h. Co-cultured cells incubated with the association (SHDAg + PEG-IFN) significantly produced levels of IFN-γ, IL-2 and IL-12. On the other hand, the HBsAg alone was able to inhibit the production of IFN-γ, suggesting that this antigen may hinder the treatment exclusively with PEG-IFN.
Asunto(s)
Antivirales/farmacología , Citocinas/metabolismo , Citotoxicidad Inmunológica/efectos de los fármacos , Hepatitis D/tratamiento farmacológico , Virus de la Hepatitis Delta/inmunología , Interferones/farmacología , Polietilenglicoles/farmacología , Técnicas de Cocultivo , Antígenos de Superficie de la Hepatitis B/farmacología , Hepatitis D/inmunología , Hepatitis D/metabolismo , Hepatitis D/virología , Virus de la Hepatitis Delta/patogenicidad , Antígenos de Hepatitis delta/farmacología , Interacciones Huésped-Patógeno , Humanos , Interferón gamma/metabolismo , Interleucina-12/metabolismo , Interleucina-2/metabolismo , Células Jurkat , Transducción de Señal , Células THP-1RESUMEN
In 1991, Peru launched the first vaccination program against hepatitis B in children aged under 5 years in the hyperendemic [hepatitis B virus (HBV) and hepatitis D virus (HDV)] province of Abancay. We conducted a cross-sectional study to determine the prevalence of HBV and HDV infections, 23 years after the launch of the vaccination program, as well as the post-vaccine response against hepatitis B in terms of prevalence of hepatitis B surface antibody (anti-HBs ≥10 mUI/ml). Among 3165 participants aged from 0 to 94 years, the prevalence rates of hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (total anti-HBc) were 1.2% [95% confidence interval (CI) 0.85-1.64%], and 41.67% (95% CI 39.95-43.41%), respectively. The prevalence rate of anti-HBs at protective levels (≥10 mUI/ml) in individuals who HBsAg and anti-HBc negative was 66.36% (95% CI 64.15-68.51%). The prevalence rate of HBsAg in children aged <15 years was nil, and among adult HBsAg carriers, the prevalence of hepatitis D antibody (anti-HDV) was 5.26% (2/38; 95% CI 0.64-17.74). These findings showed that HBV prevalence has changed from high to low endemicity, 23 years following implementation of the vaccination program against hepatitis B, and HDV infection was not detected in those aged <30 years.
Asunto(s)
Vacunas contra Hepatitis B/historia , Hepatitis B/prevención & control , Hepatitis D/epidemiología , Programas de Inmunización/historia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios Transversales , Enfermedades Endémicas , Femenino , Anticuerpos Antihepatitis/sangre , Hepatitis B/epidemiología , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/farmacología , Virus de la Hepatitis B/inmunología , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Perú/epidemiología , Proyectos Piloto , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15-20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies. METHODS: A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers. RESULTS: A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits. CONCLUSIONS: The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.
Asunto(s)
Ensayo de Inmunoadsorción Enzimática/normas , Anticuerpos Antihepatitis/sangre , Hepatitis D/diagnóstico , Juego de Reactivos para Diagnóstico/normas , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Humanos , Límite de Detección , Sensibilidad y Especificidad , TaiwánRESUMEN
OBJECTIVE: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. MATERIALS AND METHODS: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. RESULTS: The prevalence rates of HBsAg, anti-HBc total, anti- HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). CONCLUSIONS: These findings show the elimination of HBVmcarriers in children <11 years, eight years following introduction of the vaccination against HBV.
OBJETIVO: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. MATERIAL Y MÉTODOS: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. RESULTADOS: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. CONCLUSIONES: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.
Asunto(s)
Anticuerpos Antihepatitis/sangre , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/epidemiología , Hepatitis D/epidemiología , Indígenas Sudamericanos/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Estudios Transversales , Femenino , Hepatitis B/inmunología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis D/inmunología , Hepatitis D/prevención & control , Virus de la Hepatitis Delta/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Indígenas Sudamericanos/etnología , Lactante , Masculino , Persona de Mediana Edad , Perú/epidemiología , Prevalencia , Distribución por Sexo , Adulto JovenRESUMEN
Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.
Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Hepatitis D/epidemiología , Indígenas Sudamericanos/estadística & datos numéricos , Anticuerpos Antihepatitis/sangre , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/epidemiología , Perú/epidemiología , Hepatitis D/inmunología , Hepatitis D/prevención & control , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Virus de la Hepatitis Delta/inmunología , Indígenas Sudamericanos/etnología , Virus de la Hepatitis B/inmunología , Prevalencia , Estudios Transversales , Distribución por Sexo , Distribución por Edad , Hepatitis B/inmunología , Hepatitis B/prevención & control , Anticuerpos contra la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangreRESUMEN
Introduction: Hepatitis D infection causes severe form of viral hepatitis in humans and only affects those with hepatitis B either as a co-infection or superinfection. The aim of this study was to determine the prevalence of Hepatitis D and its effect on the immunologic and molecular profile of Hepatitis B among asymptomatic Chronic Hepatitis B patients in Abeokuta.Methodology: A cross-sectional study of 99 chronic HBV patient who met the inclusion criteria. All the patients were tested for HBsAg, anti HCV, HDV antigen, anti HDV, HBsAg quantification, and HBV DNA quantification. Associations were tested for and P value less than 0.05 was considered significant.Results: The participants included 53 (58%) male and 38 (42%) females with ages ranging from 18 to 69 (means 39 ± 11) years. Ten (11%) participants were positive for HDV-Ag while 1 (1.1%) was positive for anti-HDV. Five (5.5%) were positive for HIV 1 &2 while 1 (1.1%) was positive for anti HCV. HBV DNA quantification ranged from 15 to 17,000,000 IU/ml while HBsAg quantification ranged from 0.25 to45,520 IU/ml. There was no statistically significant relationship between HDV-Ag and age (p = .51), sex (p = .73), HBV DNA (p = .8) and HBsAg quantification (p = 1).Conclusion: The prevalence of HDV-Ag among asymptomatic treatment naïve chronic hepatitis B patients in Abeokuta was 11% and there was no significant difference in the levels of HBV DNA and HBsAg among those with or without hepatitis D.