Identificación del virus de hepatitis delta genotipo 3 en comunidades andinas y amazónicas del Perú

Introducción. El virus de la hepatitis delta (VHD) es el causante de la forma más severa de la hepatitis viral humana, se asocia con un riesgo alto de fibrosis al hígado y carcinoma hepatocelular (HCC). Existen 8 genotipos del VHD con diferente distribución geográfica. Objetivos. Identificar los genotipos del VHD circulante en Huanta y tres pueblos indígenas de la Amazonía peruana. Métodos. Estudio observacional y transversal, realizado en 582 muestras reactivas para anti-HBc del VHB. Por el método nRT-PCR se procesaron todos los anti VHD positivos, el genotipo fue determinado mediante secuenciamiento directo tipo Sanger y análisis filogenético del fragmento R0. Se utilizaron 111 secuencias de referencia del GenBank. Las 42 secuencias del estudio fueron editadas y ensambladas con programas bioinformáticos. El análisis filogenético y evolutivo se realizó con los programas: Beast V2.5.2, Jmodeltest v2.1.10, Tracer v1.7.1, Tree Annotator y Figtree v1.4.4. Se utilizaron los modelos Bayesianos Yule y Birth Death skyline serial, el MCMC en 30 y 80 millones respectivamente, con el relaxed uncorrelated Exponential molecular clock. Se calcularon las medidas de resumen y de tendencia central utilizando el programa en STATA 14.0. Resultados. La media de la edad fue de 38 años, el 52,8% fueron mujeres. 101 muestras fueron positivas para anticuerpos anti-VHD. El ARN del VHD fue detectado en el 49,5% de las muestras reactivas a ELISA anti-VHD. El análisis filogenético determinó la presencia del genotipo 3. Conclusiones. Se evidencia la presencia del genotipo 3 del VHD en comunidades andinas y amazónicas del Perú.

Introduction. The Hepatitis Delta Virus (HDV) is the cause of the most severe form of human viral hepatitis and is associated with a high risk of liver fibrosis and hepatocellular carcinoma (HCC). There are 8 HDV genotypes with different geographic distribution. Objectives. To identify the genotypes of VHD circulating in Huanta and three indigenous peoples of the Peruvian Amazon. Methods. Observational and cross-sectional study, from 582 reactive samples for anti-HBc-HBV. Anti-HDV positive samples were processed with the nRT-PCR method, genotype was determined by direct Sanger-type sequencing and phylogenetic analysis of the R0 fragment. 111 reference sequences from GenBank were used. The 42 sequences of the study were edited y assembled with the bioinformatics programs. Phylogenetic and evolutionary analysis was performed with the following software: Beast v2.5.2, Jmodeltest v2.1.10, Tracer v1.7.1, Tree Annotator and Figtree v1.4.4. The Bayesian Yule and Birth Death skyline serial models were used, the MCMC at 30 and 80 million respectively, with the relaxed uncorrelated Exponential molecular clock. Summary and central tendency measures were calculated using the program in STATA 14.0. Results. The mean age was 38 years, 52.8% were women. 101 samples were positive for anti-HDV antibodies. HDV RNA was detected in 49.5% of the anti-HDV ELISA reactive samples. Phylogenetic analysis determined the presence of genotype 3. Conclusions. The presence of HDV genotype 3 in Andean and Amazonian communities of Peru is evidenced.

Systemic Inflammatory Molecules Are Associated with Advanced Fibrosis in Patients from Brazil Infected with Hepatitis Delta Virus Genotype 3 (HDV-3).

BACKGROUND AND AIMS: Hepatitis Delta virus (HDV) genotype 3 is responsible for outbreaks of fulminant hepatitis in Northeastern South America. This study investigates if systemic inflammatory molecules are differentially expressed in patients with advanced fibrosis chronically infected with Hepatitis Delta virusgenotype 3(HDV-3). METHODS: Sixty-one patients from the north of Brazil coinfected with hepatitis B virus (HBV)/HDV-3 were analyzed. HDV quantification and genotyping were performed by semi-nested real-time polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) methodologies. Ninety-two systemic inflammatory molecules (SIMs) were measured by Proximity Extension Assay (PEA) technology. The Shapiro-Wilk, Student's t-test, Mann-Whitney tests, and logistic regression analysis were used when appropriate. RESULTS: The median age was 41 years, and all patients were HBeAg negative. Advanced fibrosis or cirrhosis was diagnosed by histological staging in 17 patients, while 44 presented with minimal or no fibrosis. Advanced necroinflammatory activity correlated positively with serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Established non-invasive fibrosis scores (APRI, FIB-4, and AST/ALT ratio) revealed low sensitivities and positive predictive values (PPVs) with an AUROC maximum of 0.586. Among the 92 SIMs analyzed, MCP.4, CCL19, EN.RAGE, SCF, and IL18 showed a positive correlation with fibrosis stage. A combined score including CCL19 and MCP.4 revealed a sensitivity of 81% and an odds ratio of 2.202 for advanced fibrosis. CONCLUSIONS: Standard non-invasive fibrosis scores showed poor performance in HDV-3 infection. We here suggest that the determination of CCL19 and MCP.4 may be used to identify patients with advanced fibrosis. Moreover, this study gives novel insights into the immunopathogenesis of HDV-3 infection.

Magnitude and genotype of hepatitis delta virus among chronic hepatitis B carriers with a spectrum of liver diseases in Ethiopia.

INTRODUCTION AND OBJECTIVES: Chronic hepatitis D infection contributes substantially to the progression of chronic liver disease, especially in most low and middle-income countries, where hepatitis B virus-related chronic liver disease is endemic. Therefore, this study aimed to determine the magnitude and genotype of hepatitis delta virus (HDV) among patients with chronic hepatitis B (CHB)-related liver diseases in Ethiopia. PATIENTS AND METHODS: In this cross-sectional study, 323 known HBsAg positive individuals comprising 220 patients with CHB-related liver diseases [121 advanced liver diseases (hepatocellular carcinoma /HCC/ and non-HCC) and 99 chronic hepatitis (CH)], and 103 symptomless blood donors (BD) were enrolled. An ELISA kit was employed to determine HDV infection, and quantitative real-time PCR was used to detect HDV RNA. In addition, a non-coding genomic RNA region was sequenced for genotyping and phylogenetic analysis. RESULTS: Irrespective of the stage of liver disease, the overall magnitude of HDV was 7.7% (25/323). The frequency of anti-HDV increases with the severity of liver disease, 1.9%, 4%, 10%, and 21.3% among BD, CH, non-HCC, and HCC patients, respectively. HDV RNA has been detected in 1.54 %(5/323) cases with a mean viral load of 4,010,360 IU/ml. All isolates were found to be HDV genotype 1. CONCLUSIONS: The magnitude of HDV infection increased with the severity of liver disease, indicating HDV infection is more common among patients with CHB-related liver diseases in Ethiopia.

Prevalence of hepatitis B, C, and D virus infection in Haiti: A systematic review and meta-analysis.

Background: Viral hepatitis causes an important global health burden. In 2016, the World Health Assembly adopted an objective to globally eliminate this as a public health threat by 2030. However, significant gaps exist between countries in their progress. Haiti is the last country that has introduced infant hepatitis B vaccines into the routine immunization program in the Region of the Americas, and its schedule still does not incorporate birth dose vaccines. As the first step to raise awareness of viral hepatitis in this country, we conducted a systematic review and meta-analysis to estimate the prevalence of hepatitis B (HBV), C (HCV), and D (HDV) viruses in Haiti. Methods: We searched PubMed, EMBASE, Web of Science and Scopus for studies reporting the prevalence of HBV, HCV and HDV among Haitian, with no language restriction, published until November 30th, 2021. Prevalence was pooled via a random-effects meta-analysis using a generalized linear mixed model with the logit link. Results: Of 453 articles retrieved, 25 studies were included: 16 reported the prevalence of hepatitis B surface antigen (HBsAg), three for anti-HCV antibody, and six for both HBsAg and anti-HCV. No study was found for HDV prevalence. The pooled prevalence of HBsAg was 0.7% [95% confidence interval (CI): 0.3-1.4, I 2 = 77.7%] among children, 3.5% (95% CI: 2.8-4.4, I 2 = 93.2%) in the general adult population and 7.4% (95% CI: 4.0-13.3, I 2 = 83.9%) in high-risk adult population. The pooled prevalence of anti-HCV antibody was 0.9% (95% CI: 0.6-1.4, I 2 = 93.5%) among the general population and 1.4% (95% CI: 0.4-4.2, I 2 = 0.0%) in high-risk adult population. No study reported the prevalence of anti-HCV antibody exclusively in children. Interpretation: The prevalence of blood-borne hepatitis, particularly that of HBV, is substantial in Haiti. The introduction of birth dose hepatitis B vaccines and improving access to testing and treatment services should be urgently considered to meet the elimination goal. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022298081, identifier: PROSPERO (CRD42022298081).

Seroprevalence of hepatitis B, C and D markers in indigenous patients seen at the Native American Outpatient Clinic of Universidade Federal de São Paulo

ABSTRACT Objective To detect and treat cases of viral hepatitis B, C and D in patients seen at the Native American Outpatient Clinic of Universidade Federal de São Paulo. Methods This sample comprised 81 indigenous recruited between 2018 and 2020. Volunteers were aged 7 months to 70 years (mean age of 28±20 years), belonged to 26 ethnic groups spanning the Brazilian territory and answered a questionnaire, which was attached to their medical records. Peripheral blood samples (20mL) were collected, transported to the Clinical Laboratory of Hospital Israelita Albert Einstein, processed, and tested for markers of viral hepatitis B, C and D. Results In this study, 39 (48.1%) individuals were anti-HBs (+) only, 13 (16.0%) individuals were anti-HBs (+) and anti-HBc (+), and 28 (34.6%) individuals were negative for all markers. No anti-HBc IgM+ samples were found. No cases of hepatitis C and D were found. Conclusion This analysis provided evidence of previous infection by the hepatitis B virus. These findings led to prescription of vaccination against hepatitis B to all participants who were negative for all viral hepatitis B markers, given records of prior hepatitis B vaccination were unreliable.

Viral hepatitis update: Progress and perspectives.

Viral hepatitis, secondary to infection with hepatitis A, B, C, D, and E viruses, are a major public health problem and an important cause of morbidity and mortality. Despite the huge medical advances achieved in recent years, there are still points of conflict concerning the pathogenesis, immune response, development of new and more effective vaccines, therapies, and treatment. This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain to be solved, and future research directions. For hepatitis A virus we will address epidemiology, molecular surveillance, new susceptible populations as well as environmental and food detections. In the case of hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine improvement. On hepatitis C virus, we will focus on pathogenesis, immune response, direct action antivirals treatment in the context of solid organ transplantation, issues related to hepatocellular carcinoma development, direct action antivirals resistance due to selection of resistance-associated variants, and vaccination. Regarding hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy. Finally, for hepatitis E virus, we will address epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, the development of a vaccine, and environmental surveillance.

Update on the management and treatment of viral hepatitis.

This review aims to summarize the current evidence on the treatment of viral hepatitis, focusing on its clinical management. Also, future treatment options and areas of potential research interest are detailed. PubMed and Scopus databases were searched for primary studies published within the last ten years. Keywords included hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, hepatitis D virus (HDV), hepatitis E virus, and treatment. Outcomes reported in the studies were summarized, tabulated, and synthesized. Significant advances in viral hepatitis treatment were accomplished, such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A, hepatitis B, and hepatitis E vaccination. Drugs that cure hepatitis B, going beyond viral suppression, are so far unavailable; however, targeted antiviral drugs against HBV (immunomodulatory therapies and gene silencing technologies) are promising approaches to eradicating the virus. Ultimately, high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems. The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B, albeit further investigation is required. Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.

First molecular epidemiological study of hepatitis B and D in individuals infected with human T-lymphotropic virus 1/2 from Argentina.

Human T-lymphotropic virus 1/2 (HTLV-1/2), hepatitis B virus (HBV), and hepatitis D virus (HDV) share transmission routes. Argentina shows low prevalence of HTLV-1/2, HBV, and HDV infections; however, this situation may vary according to the geographic region and group studied. The aim of this study was to estimate the prevalence of HBV and HDV infections and detect both viral genotypes in HTLV-1/2 individuals from Argentina. A total of 202 HTLV-1/2 confirmed samples (blood donors [BD] and individuals with risk factors for HTLV-1/2 [RF]) were tested for HBsAg and total anti-HBc by enzyme-linked immunosorbent assay. All reactive samples for some HBV markers were analyzed for HBV DNA characterization and HDV serological and molecular analysis. Total prevalence was 1.5% for HBsAg and 6.4% for anti-HBc. Prevalence was 23.1% for anti-HDV in all HBV-reactive samples. No significant difference was observed for HBV and HDV prevalence within HTLV subtypes. The population study showed that prevalence of anti-HBc was higher in the RF than in the BD population, with no significant differences between them. The HBsAg marker and anti-HDV were only found in RF, showing significant differences when compared to BD. Regarding molecular detection, one sample amplified for HBV DNA and none for HDV RNA. HBV sequence was classified as subgenotype F1b. New and updated background on serological markers of HBV and HDV infection in patients with HTLV-1/2 was provided.

Tendências e distribuição espacial da hepatite D no Norte do Brasil, 2009-2018: um estudo ecológico / Tendencias y distribución espacial de Hepatitis D en el Norte de Brasil, 2009-2018: un estudio ecológico / Trends and spatial distribution of Hepatitis D in the North of Brazil, 2009-2018: an ecological study

Objetivo: Analisar a incidência anual de hepatite D no Brasil e na região Norte, no período 2009-2018. Métodos: Estudo ecológico de casos de hepatite D notificados no Sistema de Informação de Agravos de Notificação (Sinan), analisados por sexo, idade e estados do Norte. Realizou-se análise de tendência temporal pelo método de Prais-Winsten, para estimar a variação percentual anual (VPA) das taxas de incidência. Resultados: No período, foram reportados 2.710 casos no Brasil, 74,5% na região Norte e 71,5% somente no Amazonas, Acre e Rondônia. Houve tendência de queda da VPA no país (-21,6% - IC95% -3,8;-36,2%), região Norte (-28,5% - IC95% -5,2;-46,1%,), Amazonas (-34,1% - IC95% -0,8;-56,2%) e Acre (-37,6% - IC95% -18,0;-52,6%). Verificou-se diminuição de casos nos estratos etários abaixo de 40 anos. Conclusão: Houve tendência de queda da incidência de hepatite D na Amazônia Ocidental, que impactou na incidência no país. Essa redução foi puxada pelos mais jovens, provavelmente resultado da vacinação para hepatite B.

Objetivo: Evaluar la incidencia anual de casos de hepatitis D en Brasil y en la Región Norte, entre 2009-2018. Métodos: En este estudio ecológico, se utilizaron casos notificados al Sistema Nacional de Agravamiento de de Enfermedades (Sinan), analizados por sexo, edad y estados del Norte. Se utilizó la regresión de Prais-Winsten para análisis de la tendencia temporal y el cálculo de la variación porcentual anual (VPA) de tasas de incidencia. Resultados: En el periodo, se notificaron 2.710 casos, siendo 74,5% en el Norte e 71,5% en Amazonas, Acre y Rondônia. Hubo tendencia a disminución de la VPA en Brasil (-21,6% - IC95% -3,8;-36,2%), región Norte (-28,5% - IC95% -5,2;-46,1%,), Amazonas (-34,1% - IC95% -0,8;-56,2%) y Acre (-37,6% - IC95% -18,0;-52,6%). Hubo disminución de casos entre los menores de 40 años. Conclusión: Hubo tendencia a la disminución de la incidencia en la Amazonía Occidental, impactando en la incidencia en Brasil. Esta baja está relacionada con los más jóvenes, probablemente debido a la vacunación contra la hepatitis B.

Objective: To analyze the annual incidence of hepatitis D cases in both Brazil and the Brazilian Northern region between 2009 and 2018. Methods: This was an ecological study of hepatitis cases notified on the Notifiable Health Conditions Information System (SINAN), analyzed by sex, age groups, and Northern region states. Temporal trend analysis was performed using the Prais-Winsten method to estimate incident rate annual percent change (APC). Results: In the period studied, 2,710 cases were reported in Brazil, 74.5% of them in the Northern region and 71.5% in Amazonas, Acre and Rondonia alone. APC showed a downward trend in Brazil as a whole (-21.6% - 95%CI -3.8;-36.2%), in the Northern region (-28.5% - 95%CI -5.2;-46.1%,), in Amazonas (-34.1% - 95%CI -0.8;-56.2%) and in Acre (-37.6% - 95%CI -18.0;-52.6%). Cases decreased in age groups below 40 years old. Conclusion: There was a downward trend in incidence in the Western Amazon, impacting incidence in Brazil as a whole. This fall was led by younger people, probably due to hepatitis B vaccination.

Prevalence of hepatitis B and D virus infection in a district of Mato Grosso, bordering Amazonas and Rondônia states

Abstract INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.

Hepatitis B and Delta: clinical aspects of patients in the Brazilian Western Amazonia / Hepatitis B y Delta: aspectos clínicos de pacientes en el Amazonas brasileño Occidental / Hepatite B e Delta: aspectos clínicos de pacientes na Amazônia Ocidental brasileira

ABSTRACT Objective: to analyze clinical, serological, biochemical and hematological aspects in patients infected with the hepatitis B (HBV) and Delta (HDV) viruses. Method: cross-sectional, descriptive and retrospective study, performed with patients chronically infected with HBV and superinfected with HDV. Results: among the 112 patients selected, 74% were monoinfected with HBV (Group HBV) and 26% were superinfected with HDV (Group HBV+HDV). There was no difference in gender distribution. The average age was 36 years with standard deviation of ±12 years. The symptoms and signs presented a higher proportion in Group HBV+HDV (p=0.001). In both groups, most patients had non-reactive AgHBe. The records of biochemical and hematologic changes showed highest proportion in Group VHB+VHD Group (p<0.05). Conclusion: the study found that patients were in clinical stages of the disease different from those in the initial examination for monitoring their chronic condition. The clinical profile suggests greater severity of liver disease among the patients superinfected with HDV.

RESUMEN Objetivo: Analizar los aspectos clínicos, serológicos, bioquímicos y hematológicos de pacientes infectados por el virus de las hepatitis B (VHB) y Delta (VHD). Método: Se trata de un estudio transversal, descriptivo, retrospectivo, realizado entre pacientes crónicos infectados de VHB y sobre infectados de VHD. Resultados: Entre los 112 pacientes seleccionados, el 74% estaba mono infectado por VHB (Grupo VHB) y el 26%, sobre infectado por VHD (Grupo VHB+VHD). No se encontró diferencia en la distribución por género. La edad promedio era 36 años, con desviación típica de ±12 años. Los síntomas y signos sobresalían en mayor proporción en el grupo VHB+VHD (p=0,001). Para ambos grupos, la mayoría de los pacientes estaba con AgHBe no reactivo. El registro de alteraciones bioquímicas y hematológicas atribuyó proporción más grande al grupo VHB+VHD (p<0,05). Conclusión: El estudio demostró que los pacientes, en la consulta inicial para el seguimiento de la condición crónica, estaban en diferentes estadios clínicos de la enfermedad. El perfil clínico sugiere que la gravedad de la enfermedad hepática es mayor entre pacientes sobre infectados de VHD.

RESUMO Objetivo: Analisar aspectos clínicos, sorológicos, bioquímicos e hematológicos entre pacientes infectados por vírus das hepatites B (VHB) e Delta (VHD). Método: Estudo transversal, descritivo, retrospectivo, realizado com pacientes cronicamente infectados por VHB e superinfectados por VHD. Resultados: Entre os 112 pacientes selecionados, 74% estavam monoinfectados por VHB (Grupo VHB) e 26% superinfectados por VHD (Grupo VHB+VHD). Não houve diferença na distribuição por gênero. A idade média foi de 36 anos, com desvio padrão de ±12 anos. Os sintomas e sinais apresentaram maior proporção no grupo VHB+VHD (p=0,001). Para ambos os grupos, a maioria dos pacientes estava com AgHBe não reagente. O registro de alterações bioquímicas e hematológicas apresentou maior proporção no grupo VHB+VHD (p<0,05). Conclusão: O estudo revelou que os pacientes estavam em diferentes estágios clínicos da doença na consulta inicial para acompanhamento de condição crônica. O perfil clínico sugere maior gravidade da doença hepática entre os pacientes superinfectados por VHD.

Non-F HBV/HDV-3 coinfection is associated with severe liver disease in Western Brazilian Amazon.

The clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse-transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort ( P < 0.01). Women were significantly younger (39.8 years; 8-77 years) than males (44.7 years; 12-79 years; P < 0.01). Sixty-eight (18%) patients were infected with HBV-F genotype and 264 (69.8%) with HBV/non-F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94; P = 0.015). HDV-3 was the most prevalent (88.9%) genotype. Almost 70% of HDV-3 coinfected patients were infected with HBV/non-F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV-3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.

Molecular epidemiology of Hepatitis delta virus infection in Minas Gerais state from Brazil, an area outside the hyperendemic region of the Amazon Basin

BACKGROUND Hepatitis delta virus (HDV) infections in hepatitis B virus (HBV) carriers are the most severe form of viral hepatitis. HDV prevalence is high in the Brazilian Amazon, but studies in other regions of the country are still scarce and often underestimated its prevalence by including a small numbers of individuals. OBJECTIVE This study aimed to determine the serological prevalence of hepatitis D, the genotypes circulating and to evaluate the associated risk factors for acquisition of HDV in Minas Gerais state, Brazil. METHODS We screened plasma samples (n = 498) from HBV chronic carriers for anti-HD antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. For those samples that were positive for anti-HD antibodies, we performed a reverse transcriptase (RT) nested-polymerase chain reaction (nested-PCR) in order to detect the viral genome and identify the viral genotypes circulating in the state. FINDINGS The prevalence was 6.22% (31/498). Blood transfusion was the only risk factor associated with HDV infection [risk ratio: 3.73; 95% confidence interval (CI): 1.44 to 9.65]. For 26 anti-HD positive patients, HDAg gene sequences were determined and in all patients HDV genotype 1 was found. CONCLUSIONS This study confirmed the circulation of HDV in Minas Gerais, an area previously considered non-endemic for hepatitis D in Brazil. The prevalence found in this study is much higher when compared to other studies performed in Brazil, probably because the population in our study was selected with minimal bias. Furthermore, in 26 anti-HD positive plasma samples, we were also able to detect the viral genome, indicating that these patients were experienced an active infection at the time of sample collection. These findings emphasise the importance of anti-HD testing in HBV infected individuals, which may contribute to this disease control in Brazil.

Determination of hepatitis B, C and D prevalence among urban and Amerindian populations from the Eastern Brazilian Amazon: a cross sectional study.

BACKGROUND: This study was conducted to determine the prevalence of HBV, HCV, and HDV in urban populations and Amerindians living in the state of Tocantins (Eastern Amazon). METHODS: A total of 948 individuals were recruited in Tocantinopolis city (Tocantins state) of whom 603 were Amerindians (from 6 tribes) and 345 were non-Amerindians (6 urban areas of Tocantinópolis city). Anti-HCV, HBsAg, anti-HBc, anti-HBs, anti-HBc IgM, anti-HBe, HBeAg, and anti-delta antibodies were determined using enzyme immunoassay. RESULTS: HBV cleared infection (both anti-HBc/anti-HBs+), chronic inactive/immune controlled HBV infection (anti-HBc + only), previous HBV vaccination (anti-HBs + only), active HBV infection (HBsAg+), individuals susceptible to HBV, and anti-HCV reactivity were found in 12.9, 1.8, 27.2, 0.5, 57.7, 1.2% in Amerindians and 12.1, 2.0, 37.1, 0.3, 55.4, 0.3% in non-Amerindians respectively. Out of 139 anti-HBc reactive individuals, 70 were anti-HBe reactive and none presented HBeAg or anti-HBc IgM. Anti-HBc prevalence was associated to older age (p < 0.0001). Overall anti-Delta prevalence was 0.3% and regarding anti-HBc reactive individuals, anti-delta prevalence was 3.4 and 0% in Amerindians and non-Amerindians respectively. CONCLUSIONS: Overall low prevalence of HBV and HCV infection was found in the populations studied, but high HBV and HCV prevalence was observed in Amerindians compared to non-Amerindians suggesting that these individuals have a higher likelihood of acquiring to these infections. Anti-delta antibodies were found among Amerindians from Eastern Amazon suggesting a risk for this population. Of note is that nearly half of Amerindians had no anti-HBs, indicating a need for HBV vaccination campaigns in this population.

Atypical crusted scabies in a patient with chronic liver disease caused by hepatitis B and D viruses

Abstract: Crusted scabies is a less common variant of scabies that is highly contagious, difficult to treat and involves infestation by Sarcoptes scabiei var. hominis. The classical clinical presentation includes crusted, scaly and generally non-pruritic lesions usually located on the head, neck, palmar, plantar and periungual region. It was first described in Norway in 1848 in patients with leprosy who presented with crusted lesions. In this study, we report the case of a patient with crusted scabies with florid clinical manifestations and chronic liver disease due to hepatitis B and delta virus infection.

Epidemiología molecular y diversidad viral de HBV y HDV / Molecular epidemiology and viral diversity of HBV and HDV

INTRODUCCIÓN La infección por el virus de la hepatitis B (VHB) es un problema de salud pública mundial. El virus de la hepatitis D (HDV) requiere la función auxiliar de HBV para su ensamblaje y transmisión. Argentina muestra una baja prevalencia de infecciones por VHB y VHD, pero esto puede variar según la región geográfica y el grupo vulnerable buscado. OBJETIVO Estudiar la epidemiología molecular del HBV y HDV en una población hospitalaria del conurbano bonaerense y observar marcadores de infección eventualmente asociados. METODOLOGÍA Se realizó un estudio molecular de 152 muestras de plasma con marcadores de infección por HBV. Para ello, se extrajo ADN y se amplificó la región parcial del S/P y preC/C de HBV por PCR y n-PCR, respectivamente. Para estudiar HDV en el total de muestras, se extrajo ARN y se amplificó la región parcial Delta por n-PCR además se realizó serológica para HDV por Elisa (anti-HDV; Abott). Las muestras positivas se secuenciaron y los árboles filogenéticos de distancia (N-J) se construyeron con el programa MEGA. Para analizar otros marcadores de infección asociados se utilizaron ELISAs para HCV y HIV (Abbott). RESULTADOS Del total muestras analizadas con HBsAg y/o anticuerpos anti-HBc reactivos, se detectaron 21 casos positivos para las regiones S/P y/o preC-C de HBV. A partir del análisis filogenético, se observó la circulación de los subgenotipos A1, A2, D3, F1b, F3 y F4. Para HDV, fueron 40 los casos positivos de los cuales 8 fueron secuenciados, clasificando todos ellos dentro del genotipo 1. La prevalencia para anti-HDV fue 1,97% y para marcadores virales asociados se observó un 11,84% para anti-HCV y un 7,23% para HIV. DISCUSIÓN Se registró la circulación de diferentes genotipos de HBV y HDV previamente descripto en nuestro país. Los datos de prevalencia de HCV, HDV y HIV en individuos con marcadores serológicos de HBV demuestran la importancia de realizar el monitoreo de estos virus en esta población

Evidências científicas sobre a hepatite Delta no Brasil: revisão integrativa da literatura / Scientific evidence on hepatitis Delta in Brazil: integrative literature review

Resumo Objetivo: Descrever o nível de evidência científica sobre a infecção por vírus da hepatite Delta (VHD) no Brasil. Métodos: Revisão integrativa da literatura, com buscas realizadas nas bases de dados do Medical Literature Analysis and Retrieval System Online, Literatura Latino-americana e do Caribe em Ciências da Saúde, Scientific Eletronic Library Online e Scopus, com análise centrada no nivelamento do rigor metodológico de acordo com o modelo de Melnyk e Fineout-Overholt. Resultados: A busca revelou uma média de duas publicações por ano no intervalo entre 1987 e 2017. Foram selecionados 33 artigos, tendo a maioria (91%) apresentado nível de evidência VI. As publicações ficaram concentradas em periódicos da área de medicina tropical (46%) e virologia (15%). Dos trabalhos, 85% tinha profissional médico com autor e o delineamento mais encontrado foi o descritivo/transversal (69,6%). Conclusão: A produção científica sobre a infecção por VHD no Brasil está centrada em estudos de prevalência, mostrando-se incipiente quanto à produção de estudos com delineamentos mais rígidos como ensaios clínicos.

Abstract Objective: Describe the level of scientific evidence on infections by the hepatitis Delta virus (HDV) in Brazil. Methods: Integrative literature review, with research in the databases of the Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Center on Health Sciences Information, Scientific Eletronic Library Online and Scopus, with analysis focusing on the leveling of the methodological rigor according to the model of Melnyk and Fineout-Overholt. Results: The search revealed an average of two publications a year between 1987 and 2017. We selected 33 articles, the majority (91%) presented level of evidence VI. The publications were concentrated in the area of tropical medicine (46%) and virology (15%). The authors of 85% of the studies were medical professionals and the most common design was the descriptive/cross-sectional (69.6%). Conclusion: Scientific literature on HDV infections in Brazil is focused on prevalence studies, showing incipiency regarding the production of studies with stricter guidelines, such as clinical trials.

Chronic hepatitis B and D: prognosis according to Child-Pugh score / Hepatitis crónicas B y D: pronóstico según escore Child-Pugh / Hepatites crônicas B e D: prognóstico segundo escore Child-Pugh

ABSTRACT Objective: compare chronic hepatitis B patients to those superinfected with hepatitis D virus, according to Child-Pugh score regarding disease severity. Method: retrospective descriptive study, performed with 59 patients followed in the ambulatory, of which 22 (37.3%) were chronically infected with hepatitis B virus (Group HBV) and 37 (62.7%) superinfected with Delta virus (Group HBV+HDV); variables of sex, age and items of Child-Pugh score were collected by consulting medical records. Results: out of the patients, 57.6% were male, with a mean age of 30.5 years. Score A, which indicates lesser severity, was found in 100% of group HBV and 78.4% of group HBV+HDV. Score B, which indicates greater severity, was found only in group HBV+HDV in 21.6% of the patients. Conclusion: by means of the Child-Pugh score, it was observed that patients with superinfection by HDV tended to present a worse prognosis.

RESUMEN Objetivo: comparar los pacientes con hepatitis B crónica con superinfectados por el virus D según escore de Child-Pugh cuanto a la gravedad de la enfermedad. Método: estudio descriptivo retrospectivo, realizado con 59 pacientes acompañados en ambulatorio, siendo 22 (37,3%) crónicamente infectados por el virus de hepatitis B (Grupo VHB) y 37 (62,7%) con superinfección por virus Delta (Grupo VHB+VHD); fueron colectadas variables cuanto al sexo, edad y referentes al escore de Child-Pugh por medio de consulta a prontuarios. Resultados: entre los pacientes 57,6% era de varones, con edad media de 30,5 años. El escore A, que indica menor gravedad, fue encontrado en 100% del grupo VHB y 78,4% del grupo VHB+VHD. El escore B, que indica mayor gravedad, fue encontrado apenas en el grupo VHB+VHD en 21,6% de los pacientes. Conclusión: por medio del escore de Child-Pugh, se observó que los pacientes con superinfección por VHD tienden a presentar peor pronóstico.

RESUMO Objetivo: comparar os pacientes com hepatite B crônica com superinfectados pelo vírus D segundo escore de Child-Pugh quanto à gravidade da doença. Método: estudo descritivo retrospectivo, realizado com 59 pacientes acompanhados em ambulatório, sendo 22 (37,3%) cronicamente infectados pelo vírus da hepatite B (Grupo VHB) e 37 (62,7%) com superinfecção por vírus Delta (Grupo VHB+VHD); foram coletadas variáveis quanto ao sexo, idade e referentes ao escore de Child-Pugh por meio de consulta a prontuários. Resultados: entre os pacientes 57,6% era do sexo masculino, com idade média de 30,5 anos. O escore A, que indica menor gravidade, foi encontrado em 100% do grupo VHB e 78,4% do grupo VHB+VHD. O escore B, que indica maior gravidade, foi encontrado apenas no grupo VHB+VHD em 21,6% dos pacientes. Conclusão: por meio do escore de Child-Pugh, observou-se que os pacientes com superinfecção por VHD tendem a apresentar pior prognóstico.

A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required?

BACKGROUND: Hepatitis delta virus infection occurs as acute co-infection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma. CASE REPORT: We report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis. CONCLUSIONS: In patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.

Liver transplantation in a patient with hepatitis B, C and D coinfection associated with hepatocellular carcinoma: a management strategy for a rare condition. Case report / Transplante hepático em paciente com coinfecção pelos vírus B, C e D associada a carcinoma hepatocelular: uma estratégia de tratamento para uma condição rara. Relato de caso

CONTEXT: Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage liver disease. Cirrhosis due to hepatitis C infection is the leading indication for liver transplantation worldwide. However, patients who are given transplants because of viral liver diseases often present clinical coinfections, including hepatitis B together with hepatitis D. Currently, different strategies exist for patient management before and after liver transplantation, and these are based on different protocols developed by the specialized transplantation centers. CASE REPORT: We present a rare case of a 58-year-old man with chronic hepatitis B, C and D coinfection. The patient developed cirrhosis and hepatocellular carcinoma. His treatment comprised antiviral therapy for the three viruses and OLT. The patient's outcome was satisfactory. CONCLUSION: OLT, in association with antiviral therapy using entecavir, which was administered before and after transplantation, was effective for sustained clearance of the hepatitis B and D viruses. A recurrence of hepatitis C infection after transplantation responded successfully to standard treatment comprising peginterferon alfa-2A and ribavirin.

CONTEXTO: O transplante ortotópico de fígado (TOF) é o tratamento de escolha em pacientes com doença hepática terminal. A cirrose por hepatite C é a principal indicação de transplante hepático no mundo. No entanto, pacientes transplantados por hepatopatias virais frequentemente apresentam coinfecções, como hepatite B associada a hepatite D. Atualmente, existem diferentes estratégias de manejo em pacientes pré e pós-transplantados conforme diferentes protocolos de conduta de serviços especializados em transplante. RELATO DE CASO: Apresentamos o raro caso de um homem de 58 anos diagnosticado com as hepatites crônicas B, C e D. O paciente evoluiu com cirrose e carcinoma hepatocelular. O tratamento consistiu de terapia antiviral para os três vírus e de transplante ortotópico de fígado. O desfecho do paciente foi satisfatório. CONCLUSÃO: O transplante ortotópico de fígado, associado à terapia antiviral com entecavir antes e após o procedimento, foi eficaz na depuração sustentada dos vírus B e D. A recidiva do vírus C após o transplante respondeu com sucesso ao tratamento padrão com alfapeginterferon 2A e ribavirina.