Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina.

Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals coinfected with hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV). The aim of this study was to analyze the genetic diversity of HBV and to evaluate serological marker associations and coinfections with HCV and HIV in patients attending and treated in a public hospital in the province of Buenos Aires, Argentina. A total of 189 HBV reactive samples (HBsAg and/or anti-HBc) were analyzed for HBV DNA characterization. All reactive samples were tested for anti-HCV and HIV-antigen/antibody using CMIA assays. Thirty-six samples exhibited detectable HBV DNA, 7 of which were OBI. HBV sequences were classified as subgenotypes A1, A2, B2, D3, F1b, F3 and F4. Mutations related to the ability to escape the host's immune response, resistance to antiviral therapy and progression to disease were found in patients, partly due to the variable sensitivity of HBsAg, the reverse transcriptase, the basal core promoter and the preCore. HCV and HIV prevalence was 10% and most of the genotypes found in the sequences were genotype 1 and B/F recombinant subtype, respectively. Of the total samples analyzed, 7 exhibited coinfections. This study shows the frequency of OBI, subgenotype distribution, HBV mutations and coinfections, which may have important clinical implications in public hospital patients. Planned prevention, detection and treatment adherence are needed to reduce transmission and morbidity in vulnerable populations.

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.

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

Hepatitis B virus and hepatitis D virus in blood donors from Argentina: circulation of HBsAg and reverse transcriptase mutants.

In Argentina, current procedures to ensure the safety of the blood supply for transfusion include the serologic detection of specific blood-borne infections. The aim of this study was to evaluate the prevalence and the genetic diversity of hepatitis B virus (HBV) and hepatitis D virus (HDV) in blood donor populations from two distantly located Argentine regions. Data from 56,983 blood donations from the Favaloro Foundation, in the city of Buenos Aires (Central Region), and the Central Blood Bank of Misiones Province (Northeast Region) were analyzed. Samples that were reactive for HBsAg were analyzed for HBV-DNA characterization and HDV serological and molecular analysis. The HBV prevalence was 0.12 % for HBsAg and 1.68 % for anti-HBc antibodies in Buenos Aires, and 0.73 % and 8.55 %, respectively, in Misiones. Seventy-seven HBsAg-reactive samples were analyzed by polymerase chain reaction for HBV-DNA. Subgenotypes A2, B2, C2, F1b and F4 (Buenos Aires) and F1b and D3 (Misiones) were detected. Several mutations within the major hydrophilic region of HBsAg, the reverse transcriptase, the basal core promoter, and the precore/core were detected. HDV genotype 1 was identified in Buenos Aires. This study confirms the circulation of several HBV subgenotypes, as well as known and newly identified variants, and the presence of HDV1 in this population. A thorough investigation has to be carried out to evaluate the clinical importance of some of the documented mutations as well as those detected in the HDV1 case.